Effect of influenza and pneumococcal vaccines in elderly persons in years of low influenza activity Dose-Sparing H5N1 A/Indonesia/05/2005 Pre-pandemic Influenza Vaccine in Adults and Elderly Adults: A Phase III, Placebo-Controlled, Randomized Study Influenza Vaccination Is Associated With a Reduced Risk of Stroke An open-label comparison of the immunogenicity and tolerability of intranasal and intramuscular formulations of virosomal influenza vaccine in healthy adults. Lack of effect of influenza and pneumococcal vaccines on anticoagulation by warfarin. Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease: FLUCAD study. Association of Influenza Vaccination and Reduced Risk of Recurrent Myocardial Infarction Influenza vaccination and the risk of primary cardiac arrest. Influenza vaccination among the elderly in Bangkok. A rapid immune response to 2009 influenza A(H1N1) vaccines in adults: a randomized, double-blind, controlled trial. A randomized controlled trial comparing split and subunit influenza vaccines in adults in Colombia. Prevention of antigenically drifted influenza by inactivated and live attenuated vaccines. Safety and immunogenicity of 2010–2011 A/H1N1pdm09-containing trivalent inactivated influenza vaccine in adults previously given AS03-adjuvanted H1N1 2009 pandemic vaccine Safety and immunogenicity of an MF59™-adjuvanted subunit influenza vaccine in elderly Chinese subjects Influenza Vaccine Pilot Study in Acute Coronary Syndromes and Planned Percutaneous Coronary Interventions: The FLU Vaccination Acute Coronary Syndromes (FLUVACS) Study A novel influenza A (H1N1) vaccine in various age groups. Comparison of the safety and immunogenicity of 2 respiratory syncytial virus (rsv) vaccines--nonadjuvanted vaccine or vaccine adjuvanted with alum--given concomitantly with influenza vaccine to high-risk elderly individuals. Vaccination of patients with haematological malignancies with one or two doses of influenza vaccine: a randomised study Immunogenicity and safety of a booster dose of diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis vaccine (Tdap-IPV; Repevax) administered concomitantly versus non-concomitantly with an influenza vaccine (Vaxigrip) to adults aged ≥60 years: an open-label, randomised trial. Safety of influenza vaccine in heart transplant recipients. High-dose trivalent influenza vaccine compared to standard dose vaccine in elderly adults: safety, immunogenicity and relative efficacy during the 2009-2010 season. Efficacy and safety of a live attenuated influenza vaccine in adults 60 years of age and older. Two-year follow-up of the FLU Vaccination Acute Coronary Syndromes (FLUVACS) Registry. Antibody response to influenza vaccine in coronary artery disease: a substudy of the FLUCAD study. Is influenza vaccination cost effective for healthy people between ages 65 and 74 years? A randomised controlled trial. Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial. Comparison of the safety and immunogenicity of concomitant and sequential administration of an adult formulation tetanus and diphtheria toxoids adsorbed combined with acellular pertussis (Tdap) vaccine and trivalent inactivated influenza vaccine in adults. Immune response to influenza vaccination in community-dwelling Chinese elderly persons. Subunit influenza vaccines produced from cell culture or in embryonated chicken eggs: comparison of safety, reactogenicity, and immunogenicity. Antibody response to influenza immunization in coronary artery disease patients: a controlled trial. Simultaneous immunisation with influenza vaccine and pneumococcal polysaccharide vaccine in patients with chronic respiratory disease. Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome. A nasally administered trivalent inactivated influenza vaccine is well tolerated, stimulates both mucosal and systemic immunity, and potentially protects against influenza illness. Safety and efficacy of two types of influenza vaccination in heart transplant recipients: a prospective randomised controlled study. Ocular and respiratory symptoms attributable to inactivated split influenza vaccine: evidence from a controlled trial involving adults. AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial. The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial. Safety of a trivalent live attenuated intranasal influenza vaccine, FluMist, administered in addition to parenteral trivalent inactivated influenza vaccine to seniors with chronic medical conditions. A randomized, double-blind trial to evaluate immunogenicity and safety of 13-valent pneumococcal conjugate vaccine given concomitantly with trivalent influenza vaccine in adults aged ≥65 years. Influenza vaccination and vitamin K antagonist treatment: a placebo-controlled, randomized, double-blind crossover study.
Background The present prospect i ve study was conducted from 2003–2005 , among all individuals 65 years and older in Uppsala County , a region with 300 000 inhabitants situated close to the Stockholm urban area . The objective of this study was to assess the preventive effect of influenza and pneumococcal vaccination in reducing hospitalisation and length of hospital stay ( LOHS ) even during periods of low influenza activity . The specificity of the apparent vaccine associations were evaluated in relation to the influenza seasons . Results In 2003 , the total study population was 41,059 , of which 12,907 ( 31 % ) received influenza vaccine  of these , 4,447 ( 11 % ) were administered the pneumococcal vaccine . In 2004 , 14,799 ( 34 % ) individuals received the influenza vaccine and 8,843 ( 21 % ) the pneumococcal vaccine and in 2005 16,926 ( 39 % ) individuals were given the influenza vaccine and 12,340 ( 28 % ) the pneumococcal vaccine . Our findings indicated that 35 % of the vaccinated cohort belonged to a medical risk category ( mainly those persons that received the pneumococcal vaccine ) . Data on hospitalisation and mortality during the 3-year period were obtained from the administrative data base of the Uppsala county council . During the influenza seasons , reduction of hospital admissions and significantly shorter in-hospital stay for influenza was observed in the vaccinated cohort ( below 80 years of age ) . For individuals who also had received the pneumococcal vaccine , a significant reduction of hospital admissions and of in-hospital stay was observed for invasive pneumococcal disease and for pneumococcal pneumonia . Effectiveness was observed for cardiac failure even in persons that also had received the pneumococcal vaccine , despite that the pneumococcal vaccinated mainly belonged to a medical risk category . Reduction of death from all causes was observed during the influenza season of 2004 , in the 75–84-year old age group and in all age-groups during the influenza season 2005 . Conclusion The present study confirmed the additive effect of the two vaccines in the elderly , which was associated with a reduced risk in hospitalisation and a reduction in mean LOHS in seasons with low influenza activity Background . Highly pathogenic avian influenza H5N1 viruses remain a threat to human health , with potential to become p and emic agents . Methods . This phase III , placebo-controlled , observer-blinded study evaluated the immunogenicity , cross-reactivity , safety , and lot consistency of 2 doses of oil-in-water ( AS03A ) adjuvanted H5N1 A/Indonesia/05/2005 ( 3.75 μg hemagglutinin antigen ) prep and emic c and i date vaccine in 4561 adults aged 18–91 years . Results . Humoral antibody responses in the H5N1 vaccine groups fulfilled US and European immunogenicity licensure criteria for p and emic vaccines in all age strata 21 days after the second dose . At 6 months after the administration of the primary dose , serum antibody seroconversion rates continued to fulfill licensure criteria . Neutralizing cross-clade immune responses were demonstrated against clade 1 A/Vietnam/1194/2004 . Consistency was demonstrated for 3 consecutive H5N1 vaccine lots . Temporary injection-site pain was more frequent with H5N1 vaccine than placebo ( 89.3 % and 70.7 % in the 18–64 and ≥65 years strata vs 22.2 % and 14.4 % in the placebo groups ) . Unsolicited adverse event frequency , including medically attended and serious events , was similar between groups through day 364 . Conclusions . In adults and elderly adults  , AS03A-adjuvanted H5N1 c and i date vaccine was highly immunogenic for A/Indonesia/05/2005 , with cross-reactivity against A/Vietnam/1194/2004 . Temporary injection site reactions were more frequent with H5N1 vaccine than placebo , although the H5N1 vaccine was well tolerated overall . Clinical Trials Registration . NCT00616928 Background and Purpose — Vascular death rates and hospitalizations for stroke are increased during influenza epidemics . Influenza vaccination may prevent stroke . We investigated whether influenza vaccination is associated independently with reduced odds of stroke and whether effects are confined to stroke subgroups and winter seasons and shared by other vaccinations . Methods — During 18 months , we performed st and ardized interviews assessing vaccination status , risk factors , health-related behavior , and socioeconomic factors in 370 consecutive patients with ischemic or hemorrhagic stroke or transient ischemic attack ( TIA ) and 370 age- and sex-matched control subjects selected r and omly from the population . Results —  Influenza vaccination  during the last vaccination campaign was less common in patients ( 19.2 % ) than control subjects ( 31.4 % ; P<0.0001 ) . After adjustment for vascular risk factors , education , health-related behavior and other factors ,  influenza vaccination  ( odds ratio [ OR ] , 0.46 ; 95 % CI , 0.28 to 0.77 ) but not other combined recent vaccinations ( OR , 0.80 ; 95 % CI , 0.42 to 1.43 ) were associated with reduced odds of stroke/TIA . Significant effects were found in men , older subjects ( > 65 years ) , subjects with previous vascular diseases , and regarding ischemic stroke ; nonsignificant trends existed in women , younger subjects , and regarding hemorrhagic stroke . In etiologic subgroups of cerebral ischemia , similar effects were found . No protective effects were found during summer months ; however , results also varied considerably between both winter seasons examined . Conclusions — These results support the hypothesis that influenza vaccination may be associated with reduced stroke risk . However , residual confounding can not be excluded , and interventional studies are required to evaluate the role of influenza vaccination in stroke prevention BACKGROUND Many intramuscular inactivated influenza vaccines achieve suboptimal results in the prevention of respiratory disease and influenza complications . This has led to the current interest in developing effective oral or intranasal preparations . OBJECTIVE This study compared the immunogenicity and tolerability of intranasal and intramuscular formulations of virosomal subunit influenza vaccine in healthy adults . It also assessed the immunogenicity and tolerability of 3 different production lots of the intranasal vaccine containing Escherichia coli heat-labile toxin adjuvant . METHODS This was a multicenter , Phase I , r and omized , open-label pilot study in which the primary end point was immunogenicity ( hemagglutination-inhibition [ HI ] antibody assay on days 1 and 29 ) . The secondary end point was the frequency of adverse events ( AEs ) . Subjects were assigned to 4 vaccination groups : groups AI , AII , and AIII received intranasal influenza vaccine from batches that differed in the hemagglutinin and neuraminidase strains used , and group B received intramuscular virosomal subunit vaccine . Assessment s of health status , hematology , biochemistry , body temperature , heart rate , blood pressure , and incidence of AEs were made on days 1 , 8 , and 29 , and serology was assessed on days 1 and 29 . RESULTS The study enrolled 88 subjects . All 3 production lots of intranasal vaccine induced an immune response to most of the viral strains administered ( A/Singapore , A/Texas , A/Wuhan , B/Beijing ) , with no notable immunogenic differences between lots . After intranasal vaccination , geometric mean titers ( GMT ) increased 2.7-fold against A/Singapore ( group AI ) ; 1.8- and 3.1-fold against A/Texas ( groups AII and AIII , respectively ) ; 1.9- to 2.4-fold against A/Wuhan ; and 1.5- to 1.7-fold against B/Beijing . After intramuscular vaccination . GMT increased 11.3- , 6.3- , and 2.7-fold against A/Texas , A/Wuhan , and B/Beijing , respectively . Seroprotection ( HI antibody titers > or = 1:40 in > 70 % of those vaccinated ) was achieved against all strains in the group that received intramuscular vaccination , against A/Wuhan in all groups that received intranasal vaccination , and against A/Texas in group AII . Both vaccine formulations were well tolerated . Intranasal vaccination was associated with a low incidence ( < 20 % ) of nasal AEs . CONCLUSIONS Both the intranasal and intramuscular vaccinations elicited a systemic immune response and were well tolerated . The different batches of intranasal vaccine showed a similar immunogenic profile . Intranasal administration may be preferred to intramuscular administration by some patients The effects on anticoagulation of a purified trivalent sub-unit influenza vaccine and a 14-valent pneumococcal vaccine were investigated in a single-blind controlled study involving 69 well-stabilised warfarin recipients . There were no clinical ly or statistically significant alterations of anticoagulant control in vaccine recipients as compared with controls at 2 , 7 and 21 days after vaccination . On the basis of these data , concern about warfarin-vaccine interaction should not deter practitioners from immunising warfarin recipients against influenza or infection with Streptococcus pneumoniae AIMS To evaluate the effect of influenza vaccination on the coronary events in patients with confirmed coronary artery disease ( CAD ) . METHODS AND RESULTS R and omized , double-blind , placebo controlled study . We included 658 optimally treated CAD patients ; 477 men , mean age 59.9+/-10.3 years . Three hundred and twenty-five patients received the influenza vaccine  , and 333 patients  placebo . Median follow-up was 298 ( interquartile range 263 - 317 ) days . Primary endpoint was the cardiovascular death . Its estimated 12-month cumulative event rate was 0.63 % in the vaccine vs. 0.76 % in controls ( HR 1.06 95 % CI : 0.15 - 7.56 , P = 0.95 ) . There were two secondary composite endpoints : ( i ) the MACE ( cardiovascular death , myocardial infa rct ion , coronary revascularization ) tended to occur less frequently in the vaccine group vs. placebo with the event rate 3.00 and 5.87 % , respectively ( HR 0.54;95 % CI : 0.24 - 1.21 , P = 0.13 ) . ( ii ) Coronary ischaemic event ( MACE or hospitalization for myocardial ischaemia ) estimated 12-month event rate was significantly lower in the vaccine group 6.02 vs. 9.97 % in controls ( HR 0.54 ; 95 % CI : 0.29 - 0.99 , P = 0.047 ) . CONCLUSION In optimally treated CAD patients  influenza vaccination improves the clinical course of CAD and reduces the frequency of coronary ischaemic events . Large-scale studies are warranted to evaluate the effect of influenza vaccination on cardiovascular mortality . ( Clinical Trials.gov : NCT 00371098 ) Background —Numerous studies have suggested that microbial agents may promote atherosclerosis . A smaller body of research has suggested that acute respiratory infection may be a risk factor for myocardial infa rct ion ( MI ) . We hypothesized that influenza vaccine might reduce the risk of recurrent MI in patients with documented coronary heart disease ( CHD ) . Methods and Results —A case-control study was performed on 218 CHD patients seen at Memorial Hermann Hospital during the influenza season of October 1997 through March 1998 . Patients who experienced new MI were included in the case group , and those who did not experience new MI or unstable angina were assigned to the control group . Data were collected by structured review of patients ’ charts and through a subsequent telephone survey . Adjusted for history of influenza vaccination in previous years , multivariate logistic regression revealed risk of MI to be associated with current hypertension ( OR 4.96 , 95 % CI 2.06 to 11.96 , P < 0.0001 ) , hypercholesterolemia ( OR 4.08 , 95 % CI 1.67 to 9.99 , P = 0.002 ) , smoking ( OR 3.75 , 95 % CI 1.76 to 7.98 , P = 0.001 ) , and  influenza vaccination  ( OR 0.33 , 95 % CI 0.13 to 0.82 , P = 0.017 ) . Despite significant association in univariate analysis , multivitamin therapy and physical exercise were not associated with risk of reinfa rct ion in multivariate analysis . Conclusions —In this study in patients with chronic CHD , vaccination against influenza was negatively associated with the development of new MI during the same influenza season . However , to address causal inference , examination of prospect i ve data sets will be needed Influenza epidemics are associated with an excess of mortality not only from respiratory diseases but also from other causes , and cardiovascular mortality increases abruptly during influenza epidemics , with little evidence of a lag period . In a population -based case-control study , the authors examined whether influenza vaccination was associated with a reduced risk of out-of-hospital primary cardiac arrest ( PCA ) , a major contributor to cardiovascular mortality in the community . Cases of PCA ( n = 342 ) without prior heart disease or life-threatening comorbidity that occurred in King County , Washington , were identified from paramedic incident reports from October 1988 to July 1994 . Demographically similar controls ( n = 549 ) were identified from the community by using r and om digit dialing . Spouses of subjects were interviewed to assess treatment with  influenza vaccine  during the previous year and other risk factors . After adjustment for demographic , clinical , and behavioral risk factors , influenza vaccination was associated with a reduced risk of PCA ( odds ratio = 0.51 , 95 percent confidence interval : 0.33 , 0.79 ) . The authors suggest that while the association of influenza vaccination with a reduced risk of PCA is consistent with cohort studies of  influenza vaccination and total mortality , further studies are needed to determine whether the observed association reflects protection or selection This study aim ed to determine the effectiveness of influenza vaccinations among the elderly in Bangkok in reducing influenza-like illness ( ILI ) and influenza-related complications . Using a non-r and omized , controlled , prospect i ve methodology , healthy , active people aged 60 years or more , living in the Bangkok Metropolitan Administration ( BMA ) area , were studied . The two study cohorts comprised 519 persons in the vaccinated group and 520 in the non-vaccinated group . The outcome under study was influenza-like illness ( ILI ) , as reported by the study volunteers . The two groups were comparable for most socio-demographic characteristics , except for gender , level of education , marital status , and smoking habit . The age range was 60 - 88 years ( mean : 68 years ) . Females outnumbered males in both groups , with ratio of female to male of 2.6:1 and 1.9:1 in the vaccinated and non-vaccinated groups , respectively . The top three co-morbidities among these groups were hypertension , diabetes mellitus , and heart disease , in that order . Only 1 % of the volunteers reported lung disease as co-morbidity . During the 12-month study period , a total of 107 volunteers reported  ILI in both groups , with 38 persons in the vaccinated group and 69 persons in the non-vaccinated group . There were 46 ILI episodes in the vaccinated group , and 86 in the non-vaccinated group , for a total of 132 episodes . The incidence rates rates of influenza in this population , therefore , were 8.9 % for the vaccinated and 16.9 % for the non-vaccinated groups ; with a reduction in the rate of reported ILI and doctor visits of 8 % . Vaccine effectiveness was rated at 47.6 % , crude risk ratio at 1.9 ( 1.33 - 2.75 ) , and adjusted risk ratio at 1.92 ( 95 % CI : 1.25 - 2.95 ) , after adjustment for gender , marital status , education , and smoking habit . No complications due to ILI were observed in this population during the study period . Hospitalizations during this period were due to non-ILI related causes , such as cancer and accident A double-blind , r and omized , controlled trial involving 706 adults was conducted to evaluate the immunogenicity and safety of different dosages of whole-virion or split-virion H1N1 influenza vaccines with or without aluminum adjuvant . A rapid and strong immune response was induced at day 14 after the first injection . The seroprotection rates ranged from 72.7 % ( 95 % confidence interval [ CI ] , 62.7%-81.1 % ) for 5-microg whole-virion aluminum formulation to 97.0 % ( 95 % CI , 90.9%-99.7 % ) for 30-microg split-virion nonaluminum formulation . All formulations were well tolerated . The incidences of mild , moderate , and severe reactions were 71 ( 10.1 % ) , 15 ( 2.1 % ) , and 1 ( 0.1 % ) of 706 reactions , respectively . The 15-microg split-virion formulation had the best immunogenicity and safety In a two-center , comparative trial , 344 adults were r and omly assigned to receive a single dose of inactivated split-virion ( Imovax Gripe ) or sub-unit ( Agrippal S1 ) influenza vaccine ( 1999 - 2000 formulations ) . For analysis , study groups were subdivided into adult ( 18 - 60 years old ) and elderly ( over 60 years ) subjects . Blood was drawn immediately before and one month after vaccination , safety was evaluated using a blind-observer design based on reporting of solicited and unsolicited adverse events . Both vaccines were very well tolerated , had similar reactogenicity profiles , and elicited fewer reports of reactions in elderly individuals . Post-vaccination Imovax Gripe induced seroprotective antibody titers against the three vaccine strains in 94 - 99 % of adults and 88 - 97 % of elderly subjects , compared with 88 - 100 % and 88 - 98 % , respectively , of those given Agrippal S1 . In conclusion , the split-virion and sub-unit influenza vaccines had similar safety and reactogenicity profiles , and elicited satisfactory immunity in adult and elderly subjects . However , higher post-vaccination geometric mean titer ( GMT ) values in response to the B strain were seen with the split vaccine Imovax Gripe , giving it a better overall immunogenicity BACKGROUND The efficacy of influenza vaccines may decline during years when the circulating viruses have antigenically drifted from those included in the vaccine . METHODS We carried out a r and omized , double-blind , placebo-controlled trial of inactivated and live attenuated influenza vaccines in healthy adults during the 2004 - 2005 influenza season and estimated both absolute and relative efficacies . RESULTS A total of 1247 persons were vaccinated between October and December 2004 . Influenza activity in Michigan began in January 2005 with the circulation of an antigenically drifted type A ( H3N2 ) virus , the A/California/07/2004-like strain , and of type B viruses from two lineages . The absolute efficacy of the inactivated vaccine against both types of virus was 77 % ( 95 % confidence interval [ CI ] , 37 to 92 ) as measured by isolating the virus in cell culture , 75 % ( 95 % CI , 42 to 90 ) as measured by either isolating the virus in cell culture or identifying it through real-time polymerase chain reaction , and 67 % ( 95 % CI , 16 to 87 ) as measured by either isolating the virus or observing a rise in the serum antibody titer . The absolute efficacies of the live attenuated vaccine were 57 % ( 95 % CI , -3 to 82 ) , 48 % ( 95 % CI , -7 to 74 ) , and 30 % ( 95 % CI , -57 to 67 ) , respectively . The difference in efficacy between the two vaccines appeared to be related mainly to reduced protection of the live attenuated vaccine against type B viruses . CONCLUSIONS In the 2004 - 2005 season , in which most circulating viruses were dissimilar to those included in the vaccine , the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic illnesses from influenza in healthy adults . The live attenuated vaccine also prevented influenza illnesses but was less efficacious . ( Clinical Trials.gov number , NCT00133523 . Many Canadians received a novel AS03-adjuvanted vaccine during the 2009 influenza A/H1N1 p and emic . Longer term implication s of adjuvant use were unclear : would anti-H1N1 immune responses persist at high levels and , if so , could that result in increased or unusual adverse effects upon re-exposure to H1N1pdm09 antigen in the trivalent influenza vaccine ( TIV ) for 2010–11 ? To answer these questions , adults given AS03-adjuvanted H1N1pdm09 vaccine ( Arepanrix ® , GSK Canada )  9–10 mo earlier were enrolled in an evaluator-blinded , crossover trial to receive 2010–2011 non-adjuvanted TIV ( Fluviral ® , GSK Canada ) and placebo 10 d apart , in r and om order . Adverse effects were monitored for 7 d after each injection . Vaccine-attributable adverse event ( VAAE ) rates were calculated by subtracting rates after placebo from those after vaccine . Blood was obtained pre-vaccination and 21–30 d afterward to measure hemagglutination inhibiting antibody titers . In total , 326 participants were enrolled and 321 completed the study . VAAE rates were low except for myalgia ( 18.6 % ) and injection site pain ( 63.2 % ) . At baseline , H1N1pdm09 titers ≥ 40 were present in 176/325 subjects ( 54.2 % , 95 % confidence interval 48.6 , 59.7 ) , with a geometric mean titer ( GMT ) of 37.4 ( 95 % CI 32.8 , 42.6 ) . Post-immunization , 96.0 % ( 95 % CI 92.3 , 97.8 ) had H1N1pdm09 titers ≥ 40 , with GMT of 167.4 ( 95 % CI 148.7 , 188.5 ) . Responses to both influenza A strains in TIV were similar , implying no lasting effect of adjuvant exposure . In summary , titers ≥ 40 persisted in only half the participants 9–10 mo after adjuvanted p and emic vaccine but were restored in nearly all after TIV vaccination , with minimal increase in adverse effects Background The safety and immunogenicity of an MF59 ™ -adjuvanted subunit influenza vaccine ( Sub/MF59 ™ ; FLUAD ® , Novartis Vaccines ) was evaluated among elderly Chinese subjects ( ≥ 60 years of age ) . After a preliminary Phase I , open-label study ( n = 25 ) to assess safety 1–14 days post-vaccination , a comparative observer-blind , r and omised , controlled clinical trial ( n = 600 ) was performed to assess safety and immunogenicity versus a non-adjuvanted subunit influenza vaccine ( Subunit ; Agrippal ® , Novartis Vaccines ) . Subjects were r and omised ( 2:1 ) to receive Sub/MF59 ™ or Subunit . Results Both vaccines were well tolerated , with no vaccine-related serious adverse events reported during the Phase I trial . During the observer-blind study , local and systemic reactions were generally similar for both vaccines 1–22 days post-vaccination ; however , injection-site in duration was more frequent among the Subunit group ( P < 0.05 ) , and mild pain at the injection site and fever were more frequent among Sub/MF59 ™ recipients ( P ≤ 0.005 ) . Both vaccines induced a significant ( P < 0.001 ) increase in geometric mean titres ( GMTs ) for the three strains tested , versus baseline ; GMTs against A/H1N1 , A/H3N2 and B were significantly higher in the Sub/MF59 ™ group ( P = 0.034 , P < 0.001 and P = 0.005 , respectively ) . GMT ratios against A/H1N1 , A/H3N2 and B were also significantly higher in the Sub/MF59 ™ group ( P = 0.038 , P < 0.001 and P = 0.006 , respectively ) . Similarly , the percentage of subjects achieving seroprotection or seroconversion on Day 22 was greater for Sub/MF59 ™ recipients , reaching significance for A/H3N2 ( P < 0.001 ) . Conclusion MF59 ™ -adjuvanted subunit influenza vaccine is well tolerated by elderly Chinese subjects and induces a higher level of immunogenicity than a non-adjuvanted subunit influenza vaccine in this population that is at high risk of influenza-related complications . Clinical trial registryhttp://www . clinical trials.gov , Background —Recent reports have detected an increase in the number of patients with acute coronary syndromes during the flu season . In addition , the World Health Organization recommended vaccination against influenza infection for the Southern hemisphere in the winter of 2001.We evaluated the preventive impact of vaccination on subsequent ischemic events in myocardial infa rct ion patients and in subjects undergoing planned percutaneous coronary angioplasty . Methods and Results —We included 200 myocardial infa rct ion patients admitted in the first 72 hours and 101 planned angioplasty/stent ( PCI ) patients without unstable coronary artery disease , prior bypass surgery , angioplasty , or tissue necrosis , in a prospect i ve , multicenter log during the winter season . Infa rct patients received a st and ard therapy and were then r and omly allocated in a single-blind manner to either a unique intramuscular influenza vaccination or a control group . Similarly , PCI patients were allocated to either vaccination or control groups . Combined end points ( death , reinfa rct ion , and rehospitalization for ischemia ) were assessed at 6 months ’ follow-up . The first primary outcome , cardiovascular death , occurred in 2 % of the patients in the vaccine group compared with 8 % in the control group ( relative risk with vaccine as compared with controls , 0.25 ; 95 % CI 0.07 to 0.86;P = 0.01 ) . The triple composite end point occurred in 11 % of the patients in the vaccine group compared with 23 % in controls ( P = 0.009 ) . Conclusions —Influenza vaccination may reduce the risk of death and ischemic events in patients suffering from infa rct ion and those recovering from angioplasty during flu season . This response could be related to a humoral immune response with positive consequences during flu seasons BACKGROUND There is an urgent need for a vaccine that is effective against the 2009 p and emic influenza A ( H1N1 ) virus . METHODS A split-virus , inactivated c and i date vaccine against the 2009 H1N1 virus was manufactured , and we evaluated its safety and immunogenicity in a r and omized clinical trial . Subjects were between 3 and 77 years of age , stratified into four age groups . The immunization schedule consisted of two vaccinations , 21 days apart . Subjects were injected with placebo or with vaccine , with or without alum adjuvant , at doses of 7.5 microg , 15 microg , or 30 microg . Serologic analysis was performed at baseline and on days 21 and 35 . RESULTS A total of 2200 subjects received one dose , and 2103 ( 95.6 % ) received the second dose , of vaccine or placebo .  No severe adverse side effects associated with the vaccine were noted . In the nonadjuvanted-vaccine groups , injection-site or systemic reactions , most mild in nature , were noted in 5.5 to 15.9 % of subjects . Among the subjects receiving 15 microg of nonadjuvanted vaccine , a hemagglutination-inhibition titer of 1:40 or more was achieved by day 21 in 74.5 % of subjects between 3 and 11 years of age , 97.1 % of subjects between 12 and 17 years , 97.1 % of subjects between 18 and 60 years , and 79.1 % of subjects 61 years of age or older ; by day 35 , the titer had been achieved in 98.1 % , 100 % , 97.1 % , and 93.3 % of subjects , respectively . The proportion with a titer of 1:40 or more was generally highest among the subjects receiving 30 microg of vaccine , with or without adjuvant . Vaccine without adjuvant was associated with fewer local reactions and greater immune responses than was vaccine with adjuvant . CONCLUSIONS These data suggest that a single dose of 15 microg of hemagglutinin antigen without alum adjuvant induces a typically protective immune response in the majority of subjects between 12 and 60 years of age . Lesser immune responses were seen after a single dose of vaccine in younger and older subjects . ( Clinical Trials.gov number , NCT00975572 ) BACKGROUND Respiratory syncytial virus ( RSV ) has been recognized recently as an important adult pathogen . METHODS This r and omized , double-blind , placebo-controlled study was design ed to compare humoral responses to licensed trivalent influenza vaccine given concomitantly with 1 of 2 RSV vaccine formulations in persons > or = 65 years old with cardiopulmonary disease . Hemagglutinin-inhibition assays and neutralization assays were used to measure levels of antibody to influenza and RSV , respectively . Subjects with respiratory illnesses during subsequent winters were tested for RSV and influenza by reverse-transcriptase polymerase chain reaction and serologic analysis . RESULTS Neither RSV vaccine formulation had an effect on the humoral response to influenza vaccination , and both RSV vaccines were well  tolerated  by 1169 participants . The immunogenicity of the nonadjuvanted vaccine was judged superior on the basis of mean postvaccination neutralizing antibody titers ( 12.5 vs. 12.1 ) and the percentage of subjects for whom > or = 4-fold increases in neutralizing titer were observed when acute-phase and convalescent-phase serum sample s were compared ( 168 [ 44 % ] of 383 vs. 129 [ 33 % ] of 400 ) . In year 1 , the percentage of illnesses due to RSV was 7 % ( 36 of 492 illnesses ) and that due to influenza was 8 % ( 40 of 492 ) , compared with 6 % ( 11 of 189 ) due to RSV and 11 % ( 20 of 189 ) due to influenza in year 2 . The incidence of RSV infection was not significantly different in the RSV vaccine and placebo groups . CONCLUSIONS Although the safety and immunogenicity data of these RSV vaccines are encouraging , low rates of infection make it challenging to design efficacy trials An open , r and omised study was performed to determine whether two doses of influenza vaccine were more effective than one to elicit an immune response in 70 patients with haematological malignancies . The responses were not improved by two doses compared with one ( influenza A virus serotypes H1/N1 18 % vs. 22 % and H3/N2 26 % vs. 14 % ; influenza B 25 % vs. 22 % ) . The results were similar in patients with ongoing and discontinued therapy . Patients treated with monoclonal antibodies for lymphoma had very poor responses . We conclude that two doses of influenza vaccine do not improve the antibody response in patients with haematological malignancies BACKGROUND Annual influenza vaccination provides an opportunity to administer a booster dose of diphtheria , tetanus , acellular pertussis and inactivated poliomyelitis vaccine ( Tdap-IPV ) to the elderly . This study evaluated immune responses to and safety of the two vaccines administered concomitantly or sequentially to elderly individuals in France and Germany . METHODS Individuals aged ≥60 years who had received a diphtheria/tetanus booster within 5 - 15 years were r and omised ( 1:1 ) to receive either Tdap-IPV and an inactivated influenza vaccine concomitantly ( Group 1 ) or inactivated influenza vaccine then Tdap-IPV 28 - 35 days later ( Group 2 ) . Antibody titres were measured before and 28 - 35 days after each vaccination . RESULTS The mean age of r and omised individuals ( n=954 ) was 68.8 years . Post-vaccination seroprotection rates ( ≥0.1 IU/mL for diphtheria/tetanus and ≥8 1/dilution for polio ) for Group 1 were non-inferior to Group 2 for diphtheria ( 85.4 % vs. 87.5 % ) , tetanus ( both 100 % ) , polio type 1 ( 99.8 % vs. 100 % ) , polio type 2 ( both 100 % ) and polio type 3 ( 99.3 % vs. 99.8 % ) . Similarly , percentages of individuals with pertussis antibodies ≥5 EU/mL for Group 1 were non-inferior to Group 2 : pertussis toxin ( 94.3 % vs. 98.1 % ) , filamentous haemagglutinin ( 99.8 % vs. 100 % ) , pertactin ( 97.3 % vs. 96.0 % ) , fimbriae 2 and 3 ( 91.7 % vs. 89.5 % ) . Post-vaccination geometric mean titres of anti-influenza haemagglutinin antibodies for Group 1 were non-inferior to Group 2 . Adverse events following administration of Tdap-IPV were similar in both study groups , with no vaccine-related serious adverse events . CONCLUSION Tdap-IPV and inactivated influenza vaccine can be administered concomitantly in the elderly without impairing tolerability or the immune response to either vaccine BACKGROUND Influenza vaccine is recommended for heart transplant recipients , but its administration is often deferred because of anecdotal reports of rejection associated with the vaccine . We evaluated the safety of influenza vaccine  in a group of stable heart transplant recipients over a 2-year period . METHODS During the 1993 to 1994 influenza season , stable heart transplant recipients who had undergone transplantation a minimum of 1 year before study entry were r and omized to vaccination with a single dose of influenza vaccine versus no vaccination . Routine endomyocardial biopsies and postvaccination influenza serologic studies were performed between 2 and 6 weeks after enrollment/immunization . During the 1994 to 1995 season , patients were given 2 doses of influenza vaccine , separated by 3 weeks ; endomyocardial biopsies and serologic studies were performed between 2 and 6 weeks after the second immunization or enrollment ( if control subject ) . Biopsy results were evaluated with respect to vaccine response , immunosuppressive regimens , and patient demographics . RESULTS Eighteen patients were enrolled in the single vaccine trial and 10 in the booster vaccine trial . Four of 14 vaccine recipients had biopsy specimens consistent with International Society for Heart and Lung Transplantation grade s 2 to 3A as compared with 1 of 14 control subjects ( grade 2 ) ( p = .326 ) . All episodes of rejection in the vaccine recipients were asymptomatic and responded to a single course of treatment . Rejection was unrelated to the time from transplantation , doses of immunosuppression , age , or number of doses of or response to vaccine . CONCLUSIONS Influenza vaccine can be safely administered to most heart transplant recipients but may be associated with low-level histologic rejection BACKGROUND High-dose trivalent influenza vaccine was developed to improve antibody responses to influenza vaccine in the elderly and hence potentially impact favorably on influenza-associated morbidity and mortality in this population . METHODS A phase IIIb , multicenter , r and omized , double-blind , controlled trial was conducted to compare High-Dose ( HD ) trivalent inactivated influenza vaccine ( 60μg of hemagglutinin [ HA ] per strain ) to st and ard dose ( SD ) vaccine ( 15μg of HA per strain ) in adults ≥65 years of age . Assessment s of safety ( serious adverse events [ SAE ] ) , immunogenicity ( hemagglutination inhibition [ HAI ] titers ) and relative efficacy were performed during the 2009 - 2010 influenza season , which coincided with the H1N1 p and emic . RESULTS A total of 9172 participants were enrolled in 99 research centers in the US ( 6117 and 3055 r and omized to the HD and SD groups , respectively ) . Within 180 days after vaccination , 6.7 % and 6.5 % of participants in the HD and SD vaccine groups , respectively , experienced at least one SAE , of which 0.4 % and 0.3 % had a fatal outcome . A total of 0.5 % of participants in both groups discontinued the study due to a SAE . Post-vaccination HAI titers and rate of post-vaccination HAI titer ≥1:40 were significantly higher in the HD group . No cases of influenza caused by viral types/subtypes similar to those in the vaccines were observed . All cases genetically or antigenically characterized were classified as similar to influenza A/California/7/2009 ( H1N1 ) , the p and emic strain . The vaccine efficacy of HD vaccine relative to SD vaccine against any influenza viral type/subtype was 12.6 % ( 95 % CI -140.5 ; 65.8 ) in the intent-to-treat analysis . CONCLUSION High-dose trivalent inactivated influenza vaccine is safe and well tolerated and provides superior immune responses compared to st and ard dose vaccine . Demonstration of a superior vaccine efficacy requires a separate large r and omized , controlled trial This r and omized , double-blind , placebo-controlled study investigated the efficacy , safety , and immunogenicity of LAIV in community-dwelling ambulatory adults > or = 60 years of age in South Africa in 2001 . Nose and throat swabs were obtained for influenza virus culture based on the symptoms of influenza-like illness . A total of 3242 subjects were enrolled , with a mean age of 69.5 years . The efficacy of  LAIV  against influenza viruses antigenically similar to the vaccine was 42.3 % ( 95 % CI , 21.6 - 57.8 % ) . Efficacy against A/H3N2 viruses was 52.5 % ( 95 % CI , 32.1 - 67.2 % ) ; vaccine efficacy was not observed against antigenically similar B strains . In post hoc analyses , efficacy in subjects 60 to < 70 years of age was 41.8 % and -22.7 % against A/H3N2 and B , respectively and 65.7 % and 9.9 % , respectively , for subjects > or = 70 years . Reactogenicity events were higher among LAIV than placebo recipients during 11 days postvaccination ( P=0.042 ) , including runny nose/nasal congestion , cough , sore throat , headache , muscle aches , tiredness , and decreased appetite . Rates of serious adverse events were similar for LAIV and placebo recipients . This was the first demonstration of statistically significant protection by LAIV against culture-confirmed influenza in adults > or = 60 years of age . These results suggest that LAIV may provide an additional public health tool in the prevention of influenza in the elderly . ( Clinical Trials.gov identifier , NCT00217230 . ) We have previously determined that there is a significant benefit of vaccination against influenza in patients hospitalized due to an acute coronary event . The purpose of this study is to determine whether the observed benefits of vaccination were maintained over a 2-year follow-up among those who were re-vaccinated during the subsequent winter season . During the winter season of 2001 , a total of 301 acute coronary patients were prospect ively enrolled within 72 hours of the onset of symptoms . Follow-up was conducted at 6 and 12 months . Patients who survived participated in a registry 1 year after the 2nd influenza vaccination period ( winter 2002 ) , as a cohort of chronic and stable coronary patients . The incidence of the primary endpoint cardiovascular death at 1 year was significantly lower in patients receiving vaccination than in controls ( 6 % vs 17 % , respectively ) by intention-to-treat analysis . The relative risk with vaccination  in comparison with controls was 0.34 ; 95 % confidence interval , 0.17 - 0.71 ; P = 0.002 . In the winter of 2002 , 116 patients were vaccinated according to their physicians ' instructions , and 114 subjects remained unvaccinated . The combined endpoints of total death plus myocardial infa rct ion 1 year later were 4 ( 3.4 % ) in the vaccinated group vs 11 ( 9.7 % ) among those who were not vaccinated ( P = 0.05 ) . Influenza vaccination may reduce the risk of death and ischemic events in patients admitted with acute coronary syndromes . There is also a beneficial trend in the quiescent phase of ischemia BACKGROUND Influenza vaccination is recommended for patients with cardiovascular diseases . The main reason for the low vaccination rates in such patients is insufficient knowledge about vaccination efficacy , including immune response to the vaccine . The aim of this study was to assess humoral response to influenza vaccination in patients with coronary artery disease . MATERIAL / METHODS This was a sub study of the r and omized prospect i ve double-blind placebo-controlled FLUCAD study on influenza vaccination in the secondary prevention of ischemic coronary events in patients with coronary artery disease . Patients received inactivated subunit vaccine ( n=325 ) or placebo ( n=333 ) . Anti-hemagglutinin and anti-neuraminidase antibody levels to the vaccine strains as well as IgM and IgG levels against influenza A and B were measured before administration of vaccine/placebo and after 8 - 10 weeks in 78 vaccinated and 97 placebo patients . RESULTS Post-vaccination antibody titers were significantly higher than before vaccination , with mean increases of 4.9- to 5.7-fold for anti-hemagglutinin and 3.5- to 4.2-fold for neuraminidase antibodies . Post-vaccination protection rates ranged from 56.4 to 60.3 % and response rates from 62.8 to 68 % . The percentage of patients with significant post-vaccination concentrations of IgG and IgM was higher than before vaccination and amounted to 100 % and 88.1 % in the case of IgG and 14.3 % and 5.2 % in the case of IgM in response to influenza A and B , respectively . CONCLUSIONS At least 60 % of the patients achieved high post-vaccination antibody levels sufficient to prevent influenza The aim of this study was to determine the cost effectiveness of influenza vaccination for healthy people aged 65 - 74 years living in the UK . People without risk factors for influenza ( chronic heart , lung or renal disease , diabetic , immunosuppressed or those living in an institution ) were identified from 20 general practitioner ( GP ) practice s in Liverpool in September 1999 . 729/5875 ( 12.4 % ) eligible individuals were recruited and r and omised to receive either influenza vaccine or placebo ( ratio 3:1 ) , with all participants receiving 23-valent-pneumococcal polysaccharide vaccine unless already administered . The primary analysis was the frequency of influenza as recorded by a GP diagnosis of pneumonia or influenza like illness . In 2000 , the UK vaccination policy was changed with influenza vaccine becoming available for all people aged 65 years and over irrespective of risk . As a consequence of this policy change , the study had to be fundamentally restructured and only results obtained over a one rather than the originally planned two-year r and omised controlled trial framework were used . Results from 1999/2000 demonstrated no significant difference between groups for the primary outcome ( relative risk 0.8 , 95 % CI 0.16 - 4.1 ) . In addition , there were no deaths or hospitalisations for influenza associated respiratory illness in either group . The subsequent analysis , using both national and local sources of evidence , estimated the following cost effectiveness indicators : ( 1 ) incremental NHS cost per GP consultation avoided = 2000 pound sterling ; ( 2 ) incremental NHS cost per hospital admission avoided = 61,000 pound sterling ; ( 3 ) incremental NHS cost per death avoided = 1,900,000 pound sterling and ( 4 ) incremental NHS cost per QALY gained = 304,000 pound sterling . The analysis suggested that influenza vaccination in this population would not be cost effective CONTEXT Influenza virus is a major cause of illness , disruption to daily life , and increased use of health care in all age groups . OBJECTIVE To assess the safety and effectiveness of intranasally administered trivalent , live , attenuated influenza virus ( LAIV ) vaccine for reducing illness , absenteeism , and health care use among healthy , working adults . DESIGN R and omized , double-blind , placebo-controlled trial conducted from September 1997 through March 1998 . SETTING Thirteen centers across the United States . PARTICIPANTS A total of 4561 healthy , working adults aged 18 to 64 years recruited through health insurance plans , at work sites , and from the general population . INTERVENTION Participants were r and omized 2:1 to receive intranasally administered trivalent LAIV vaccine ( n = 3041 ) or placebo ( n = 1520 ) in the fall of 1997 . MAIN OUTCOME MEASURES Episodes of febrile illness , severe febrile illness , febrile upper respiratory tract illness , work loss , and health care use during the peak and total influenza outbreak periods , and adverse events . RESULTS Recipients of LAIV vaccine were as likely to experience 1 or more febrile illnesses as placebo recipients during peak outbreak periods ( 13.2 % for vaccine vs 14.6 % for placebo ; P=.19 ) . However , vaccination significantly reduced the numbers of severe febrile illnesses ( 18.8 % reduction ; 95 % confidence interval [ CI ] , 7.4%-28.8 % ) and febrile upper respiratory tract illnesses ( 23.6 % reduction ; 95 % CI , 12.7%-33.2 % ) . Vaccination also led to fewer days of illness across all illness syndromes ( 22.9 % reduction for febrile illnesses ; 27.3 % reduction for severe febrile illnesses ) , fewer days of work lost ( 17.9 % reduction for severe febrile illnesses ; 28.4 % reduction for febrile upper respiratory tract illnesses ) , and fewer days with health care provider visits ( 24.8 % reduction for severe febrile illnesses ; 40.9 % reduction for febrile upper respiratory tract illnesses ) . Use of prescription antibiotics and over-the-counter medications was also reduced across all illness syndromes . Vaccine recipients were more likely to experience runny nose or sore throat during the first 7 days after vaccination , but serious adverse events between the groups were not significantly different . The match between the type A(H3N2 ) vaccine strain and the predominant circulating virus strain ( A/Sydney/05/97[H3N2 ] ) for the 1997 - 1998 season was poor , suggesting that LAIV provided substantial cross-protection against this variant influenza A virus strain . CONCLUSION Intranasal trivalent LAIV vaccine was safe and effective in healthy , working adults in a year in which a drifted influenza A virus predominated The annual contact for influenza vaccination provides an opportunity to ensure that adults have received other recommended vaccines such as Tdap .  Healthy 19 - 64 year-olds were r and omized to receive concomitant administration of Tdap and influenza vaccines or influenza vaccine followed ( in 4 - 6 weeks by ) Tdap .  720 participants were enrolled . No clinical ly relevant between-group differences were observed in the rates or severities of erythema , swelling , or pain at the Tdap injection site . Injection-site pain was the most commonly reported adverse event ( 66.6 % concomitant administration group versus 60.8 % sequential administration group ) ; most pain was grade d as mild and resolved by day 3 . Seroprotection and seroresponse rates for all influenza strains were comparable between the two groups . For diphtheria and tetanus , seroprotection rates and post-vaccination GMTs were non-inferior in the concomitant administration group compared to the sequential administration group . A trend for lower antibody responses to pertussis antigens PT , FHA , and FIM was observed after concomitant administration and , for PRN , this difference failed the non-inferiority criteria . While there is a small diminution in antibody response to tetanus and pertussis antigens , concomitant administration of Tdap and influenza vaccine was well tolerated and immunogenic and may offer practical advantages including convenience , compliance , and cost-savings We investigated the immune antibody response to influenza vaccine in community-dwelling Chinese elderly persons in Hong Kong . One hundred and twenty-eight subjects were recruited in a single-blind , r and omized , and placebo-controlled trial . There was no significant baseline difference between the vaccine and placebo groups regarding the seroprotection rates ( PR ) ( haemagglutination inhibition [ HI ] titre > or=1:40 ) and geometric mean titres ( GMT ) of the HI antibody titers . The PR , GMTs and serological response rates increased significantly in the vaccinated versus placebo groups in A-H1N1 at both weeks 4 and month 6 . The GMTs and serological response rates but not the PR for A-H3N2 and influenza B increased significantly in vaccinated versus placebo group at week 4 and month 6 post-vaccination . Multivariate logistic regression analyses of the seroconversion rate for A-H3N2 within the vaccinated group showed that gender , coronary heart disease and the serum albumin level were significant predictors ( p=0.018 , 0.009 and 0.025 , respectively ) . Influenza vaccination provoked a protective HI antibody response in community-living Chinese elderly persons . The mean number of unplanned hospital admissions per subject over 6 months was significantly lower in the vaccinated than in the placebo groups . Hospitalized elderly persons had poorer nutrition , 4-week post-immunization HI antibody titres and lower mini-mental state examination ( MMSE ) score than non-hospitalized elderly persons . Logistic regression analyses showed that chronic obstructive airway disease significantly increased the risk of hospitalization while the serum albumin level and 4-week A-H3N2 PR ( HI > or=40 ) were independent predictors of a decreased risk of hospitalizations BACKGROUND This study assessed the safety , reactogenicity , and immunogenicity of an injectable cell culture-derived influenza vaccine ( CCIV ) , compared with those of an injectable egg-based trivalent inactivated influenza vaccine ( TIV ) . METHODS Adult subjects ( n = 613 ; 18 to < 50 years of age ) were r and omized ( 1:1 ) to receive either CCIV or TIV .  The safety and reactogenicity of the 2 vaccines were assessed on the basis of solicited indicators and other adverse events ( AEs ) within 7 days of vaccination . All serious AEs and those AEs result ing in withdrawal were recorded throughout the study . Antibody titers were determined by the hemagglutination inhibition assay , using egg- and cell-derived antigens . Immunogenicity was assessed on the basis of the ratio of postvaccination ( day 22 ) geometric mean titers ( GMTs ) between the 2 vaccines , seroprotection rates , and seroconversion rates . RESULTS There was no clinical ly relevant difference between the safety and reactogenicity profiles of the 2 vaccines . The immunogenicity of CCIV was demonstrated to be noninferior to that of TIV on the basis of the ratio of postvaccination GMTs between the 2 vaccines . GMTs , seroprotection rates , and seroconversion rates were comparable between the 2 vaccines . CONCLUSIONS The safety , reactogenicity , and immunogenicity of the CCIV and the egg-based TIV are comparable Safety of and humoral immune response to the anti-influenza vaccine in coronary artery disease ( CAD ) patients were evaluated . The trivalent vaccine was administered to 137 eligible CAD patients and 67 age- and sex-matched healthy individuals .  Antibody ( Ab ) titers were measured before and 1 month after vaccination . CAD and HC groups were not significantly different in serologic response and magnitude of change in antibody titers against each of the vaccine antigens . In multivariate analyses , regular exercise and using multivitamin supplements were independently associated with better antibody response among CAD patients . There were no major cardiac or general adverse effects .  Influenza vaccine was found safe in CAD patients and antibody responses were similar to HCs Pneumococcal disease is an important cause of morbidity and mortality in the United Kingdom.1 The increasing numbers of elderly people and the development of drug resistant Streptococcus pneumoniae will exacerbate this problem . The safety , efficacy , and cost effectiveness of immunisation with pneumococcal polysaccharide vaccine is established,2 and immunisation is now recommended for all patients aged over 2 years with chronic lung disease , a target group for  influenza vaccination.3  Coadministration of the vaccines is recommended , though the efficacy of pneumococcal polysaccharide vaccine given in this way has been question ed.4 We examined whether an immunoresponsive interaction exists between 23 valent pneumococcal polysaccharide vaccine ( Pnu-Imune 23 ) and influenza vaccine ( Fluarix ) . One hundred and AIMS Influenza infection has been shown to accentuate the progression of atherosclerosis and precipitate the occurrence of acute coronary syndrome ( ACS ) . However , the protective effects of the influenza vaccine on cardiovascular events are still inconclusive . METHODS AND RESULTS The study was a prospect i ve r and omized open with blinded endpoint ( PROBE ) study . The 439 patients who had been admitted due to ACS within 8 weeks were enrolled and r and omly allocated to receive inactivated influenza vaccine in the vaccine group and no treatment in the control group . All patients were treated with the st and ard therapy including revascularization according to primary cardiologists . The primary endpoint , which was the combined major cardiovascular events , including death , hospitalization from ACS , hospitalization from heart failure , and hospitalization from stroke , occurred less frequently in the vaccine group than the control group [ 9.5 vs. 19.3 % , unadjusted HR 0.70 ( 0.57 - 0.86 ) , P = 0.004 ] . There was no significant difference in the incidence of cardiovascular death between the vaccine and control groups [ 2.3 vs. 5.5 % , unadjusted HR 0.39 ( 0.14 - 1.12 ) , P = 0.088 ] . CONCLUSION The influenza vaccine reduced major cardiovascular events in patients with ACS . Therefore , it should be encouraged as a secondary prevention in this group of patients A r and omized placebo-controlled double-blind trial of a nasally administered inactivated trivalent influenza vaccine formulated with partially purified meningococcal outer membrane proteins ( OMP-TIV ) was conducted in 1349 healthy adults aged 18 - 64 years . Subjects received either vaccine containing 15 μg of haemagglutinin ( HA ) of each of three influenza strains for the 2003 - 2004 season on days 0 and 14 , or 30 μg on day 0 and saline placebo on day 14 , or placebo on days 0 and 14 . Vaccination was well tolerated , with similar reactogenicity as placebo . Compared to placebo , statistically significant increases in mean serum haemagglutinin inhibition reciprocal titers and salivary secretory IgA to all 3 antigens were seen on day 28 for both vaccine dose groups . The incidence of culture-positive influenza and fever > 37.8 ° C and cough and one or more of sore throat , runny nose or nasal congestion , muscle or joint ache , headache , fatigue , or chills or culture positive influenza and at least two of these symptoms was low ( 16/1349 ; 1.2 % ) . In the intent-to-immunize population too few febrile culture-confirmed illness events ( n=4 ) occurred to perform analysis . Fever occurred infrequently , even in the presence of positive cultures and disabling multi-symptom disease . In participants receiving all doses of either vaccine regimen the incidence of culture-confirmed influenza with respiratory symptoms and with or without fever was 0.77 % ( 7/904 ) vs. 2.03 % ( 9/443 ) in placebo recipients ( p=0.045 , Fisher 's exact test ; relative risk reduction 62 % ) , despite circulation of a drift variant A/H3N2 that was poorly matched to vaccine . An OMP-TIV vaccine was well tolerated and reduced risk of symptomatic culture confirmed influenza . Vaccine efficacy will need to be vali date d in a season with a higher attack rate BACKGROUND Influenza may cause severe disease in immunosuppressed patients . Different vaccines have been proved to be efficacious to prevent influenza in tranplant recipients . Since the last five years the addition of adjuvants to improve the immune response to vaccine preparations has been proposed and evaluated . In this study , two antigenically identical vaccines , but different for the presence of adjuvants were r and omised among a cohort of heart transplant recipients to evaluate their safety and immunogenicity . METHODS 58 patients , receiving an heart transplant more than 6 months before , were r and omised to receive one shoot vaccination with Fluad ( containing the MF59 adjuvant ) or Agrippal ( no adjuvant added ) or to enter the control , not-vaccinated , group . The immune response to influenza was evaluated separately for type A and type B viruses and for the IgG and the IgM antibodies . Patients were clinical ly evaluated at least monthly up to 6 months . RESULTS Influenza symptoms were reported by 33 % of patients receiving Fluad , 29 % of the Agrippal and 63 % of the control group . 4 episodes of acute myocardial rejection > /=3A were identified without difference between the three groups . CONCLUSIONS The superior efficacy of vaccines containing adjuvants was not found and the data clearly confirmed that vaccination against influenza is safe and effective in heart transplant recipients . The use of vaccine containing adjuvant substances do not ameliorate the clinical performance of the immunisation suggesting that less expensive influenza vaccine preparation without adjuvant substances could be equally useful to protect heart transplant recipients In 2000 , an influenza vaccine  was associated with unusual ocular and respiratory symptoms ( known as " oculorespiratory syndrome " [ ORS ] ) that possibly were due to numerous microaggregates of unsplit viruses present in the product . We assessed the potential for an improved vaccine formulation ( for use in 2001 - 2002 ) to cause ORS and other symptoms in adults , using a double-blind , r and omized , crossover study design . Symptoms were ascertained 24 h after 622 doses of vaccine and 626 doses of saline placebo were injected . The risk of ORS was 6.3 % after vaccine injection and 3.4 % after placebo injection , which yielded a significant vaccine-attributable risk of 2.9 % ( 95 % confidence interval , 0.6 - 5.2 ) . ORS symptoms were mild . Significant differences in risk after injection of vaccine versus placebo existed for ocular soreness and /or itching ( 2.4 % ) , coughing ( 1.6 % ) , and hoarseness ( 1.2 % ) . Vaccine-attributable general symptoms were infrequent . We conclude that certain mild oculorespiratory symptoms were triggered by an influenza vaccine that was otherwise minimally reactogenic and , hence , that such symptoms might be associated with influenza vaccines in general BACKGROUND We aim ed to compare AS03-adjuvanted inactivated trivalent influenza vaccine ( TIV ) with non-adjuvanted TIV for seasonal influenza prevention in elderly people . METHODS We did a r and omised trial in 15 countries worldwide during the 2008 - 09 ( year 1 ) and 2009 - 10 ( year 2 ) influenza seasons . Eligible participants aged at least 65 years who were not in hospital or bedridden and were without acute illness were r and omly assigned ( 1:1 ) to receive either AS03-adjuvanted TIV or non-adjuvanted TIV . R and omisation was done in an internet-based system , with a blocking scheme and stratification by age ( 65 - 74 years and 75 years or older ) . Participants were scheduled to receive one vaccine in each year , and remained in the same group in years 1 and 2 . Unmasked personnel prepared and gave the vaccines , but participants and individuals assessing any study endpoint were masked . The co primary objectives were to assess the relative efficacy of the vaccines and lot-to-lot consistency of the AS03-adjuvanted TIV ( to be reported elsewhere ) . For the first objective , the primary endpoint was relative efficacy of the vaccines for prevention of influenza A ( excluding A H1N1 pdm09 ) or B , or both , that was confirmed by PCR analysis in year 1 ( lower limit of two-sided 95 % CI had to be greater than zero to establish superiority ) . From Nov 15 , to April 30 , in both years , participants were monitored by telephone or site contact and home visits every week or 2 weeks to identify cases of influenza-like illness . After onset of suspected cases , we obtained nasal and throat swabs to identify influenza RNA with real-time PCR . Efficacy analyses were done per protocol . This trial is registered with Clinical Trials.gov , number NCT00753272 . FINDINGS We enrolled 43 802 participants , of whom 21 893 were assigned to and received the AS03-adjuvanted TIV and 21 802 the non-adjuvanted TIV in year 1 . In the year 1 efficacy cohort , fewer participants given AS03-adjuvanted than non-adjuvanted TIV were infected with influenza A or B , or both ( 274 [ 1·27 % , 95 % CI 1·12 - 1·43 ] of 21 573 vs 310 [ 1·44 % , 1·29 - 1·61 ] of 21 482 ; relative efficacy 12·11 % , 95 % CI -3·40 to 25·29 ; superiority not established ) . Fewer participants in the year 1 efficacy cohort given AS03-adjuvanted TIV than non-adjuvanted TIV were infected with influenza A ( 224 [ 1·04 % , 95 % CI 0·91 - 1·18 ] vs 270 [ 1·26 , 1·11 - 1·41 ] ; relative efficacy 17·53 % , 95 % CI 1·55 - 30·92 ) and influenza A H3N2 ( 170 [ 0·79 , 0·67 - 0·92 ] vs 205 [ 0·95 , 0·83 - 1·09 ] ; post-hoc analysis relative efficacy 22·0 % , 95 % CI 5·68 - 35·49 ) . INTERPRETATION AS03-adjuvanted TIV has a higher efficacy for prevention of some subtypes of influenza than does a non-adjuvanted TIV . Future influenza vaccine studies in elderly people should be based on subtype or lineage-specific endpoints . FUNDING GlaxoSmithKline Biologicals SA OBJECTIVE To determine the efficacy of influenza vaccination  in elderly people . DESIGN R and omized double-blind placebo-controlled trial . SETTING Fifteen family practice s in the Netherl and s during influenza season 1991 - 1992 . PARTICIPANTS A total of 1838 subjects aged 60 years or older , not known as belonging to those high-risk groups in which vaccination was previously given . INTERVENTION Purified split-virion vaccine containing A/Singapore/6/86(H1N1 ) , A/Beijing/353/89(H3N2 ) , B/Beijing/1/87 , and B/Panama/45/90 ( n = 927 ) or intramuscular placebo containing physiological saline solution ( n = 911 ) . MAIN OUTCOME MEASURES Patients presenting with influenzalike illness  up to 5 months after vaccination ; self-reported influenza in postal question naires 10 weeks and 5 months after vaccination ; serological influenza ( fourfold increase of antibody titer between 3 weeks and 5 months after vaccination ) . RESULTS The incidence of serological influenza was 4 % in the vaccine group and 9 % in the placebo group ( relative risk [ RR ] , 0.50 ; 95 % confidence interval [ CI ] , 0.35 to 0.61 ) . The incidences of clinical influenza were 2 % and 3 % , respectively ( RR , 0.53 ; 95 % CI , 0.39 to 0.73 ) . The effect was strongest for the combination of serological and clinical influenza ( RR , 0.42 ; 95 % CI , 0.23 to 0.74 ) . The effect was less pronounced for self-reported influenza . CONCLUSION In the elderly , influenza vaccination may halve the incidence of serological and clinical influenza ( in periods of antigenic drift ) We conducted a r and omized , double-blind trial to evaluate the safety and tolerability of a live attenuated cold adapted trivalent intranasal influenza vaccine , FluMist , compared with intranasal placebo when given in addition to a licensed trivalent injected inactivated influenza vaccine ( TIV ) . The study population consisted of persons 65 years of age and older with chronic cardiovascular or pulmonary conditions or diabetes mellitus . During the 7 days post-vaccination , sore throat was reported on at least one day by 15 % ( 15/100 ) of FluMist recipients compared with 2 % ( 2/100 ) of intranasal placebo recipients ( p = 0.001 ) . No other reactogenicity symptom was statistically associated with receipt of FluMist . Among this group , FluMist was safe and well tolerated when administered with TIV This r and omized , double-blind study evaluated concomitant administration of 13-valent pneumococcal conjugate vaccine ( PCV13 ) and trivalent inactivated influenza vaccine ( TIV ) in adults aged ≥65 years who were naïve to 23-valent pneumococcal polysaccharide vaccine . Patients ( N=1160 ) were r and omized 1:1 to receive PCV13+TIV followed by placebo , or Placebo+TIV followed by PCV13 at 0 and 1 months , with blood draws at 0 , 1 , and 2 months . Slightly lower pneumococcal serotype-specific anticapsular polysaccharide immunoglobulin G geometric mean concentrations were observed with PCV13+TIV relative to PCV13 . Concomitant PCV13+TIV  demonstrates acceptable immunogenicity and safety compared with either agent given alone BACKGROUND Among millions of persons vaccinated against influenza virus each year , many are older patients treated with several drugs , including vitamin K antagonists ( VKAs ) , among which warfarin is the most commonly used . Due to high interpatient and intrapatient variability , the therapeutic dose of VKA has to be individualized by monitoring of international normalized ratio ( INR ) values . The objectives of this study were to evaluate variation in the INR and warfarin weekly dose variation after influenza vaccination administration and to follow up patients for related hemorrhagic and thrombotic events to evaluate the safety of the  influenza vaccine  and to assess the immunogenicity of the influenza vaccination  in patients receiving VKAs . METHODS One hundred four patients on a stable VKA regimen and with an indication for influenza vaccination were r and omized to receive influenza vaccination and subsequent placebo administration , or vice versa . All patients were tested for coagulation variables , clinical events , and antibody response against vaccine components . RESULTS Similar mean prothrombin times , expressed as the INR and VKA weekly dose , were found in patients after receiving vaccine or placebo . The absence of any vaccination effect on VKA treatment was confirmed using a linear mixed-effects model . The percentages of time that patients were in therapeutic range were 70.7 % after receiving vaccine and 72.4 % after receiving placebo ( P = .57 ) . There were no fatal or major bleeding events and 11 minor mucocutaneous hemorrhagic events . After vaccination , the percentage of seroprotected patients ranged from 92.0 % to 100.0 % depending on the vaccine antigen examined . CONCLUSIONS Influenza vaccination had no significant effect on INR values or warfarin sodium weekly doses . Close monitoring of INR values is not required after influenza vaccination in patients on stable long-term VKA regimens . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00222638
BACKGROUND This is an up date of the original review published in 2008 .
The risk of adverse cardiovascular outcomes is increased with influenza-like infection , and vaccination against influenza may improve cardiovascular outcomes .
OBJECTIVES To assess the potential benefits of influenza vaccination for primary and secondary prevention of cardiovascular disease .