Pneumococcal Conjugate and Plain Polysaccharide Vaccines Have Divergent Effects on Antigen-Specific B Cells Revaccination with a 23-valent pneumococcal polysaccharide vaccine induces elevated and persistent functional antibody responses in adults aged 65 > or = years. Safety of revaccination with pneumococcal polysaccharide vaccine. Use of 13-Valent Pneumococcal Conjugate Vaccine and 23-Valent Pneumococcal Polysaccharide Vaccine Among Adults Aged ≥65 Years: Recommendations of the Advisory Committee on Immunization Practices (ACIP) Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against community-acquired pneumonia in the general population aged ≥ 60 years: 3 years of follow-up in the CAPAMIS study. Randomized, Single Blind, Controlled Trial to Evaluate the Prime-Boost Strategy for Pneumococcal Vaccination in Renal Transplant Recipients Reactions after 3 or more doses of pneumococcal polysaccharide vaccine in adults in Alaska. Influence of initial vaccination with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine on anti-pneumococcal responses following subsequent pneumococcal vaccination in adults 50 years and older. Impact of infant 13-valent pneumococcal conjugate vaccine on serotypes in adult pneumonia Long-term comparative immunogenicity of protein conjugate and free polysaccharide pneumococcal vaccines in chronic obstructive pulmonary disease. Antibody persistence ten years after first and second doses of 23-valent pneumococcal polysaccharide vaccine, and immunogenicity and safety of second and third doses in older adults Revaccination with the 23-valent pneumococcal polysaccharide vaccine in middle-aged and elderly persons previously treated for pneumonia. Serological criteria and carriage measurement for evaluation of new pneumococcal vaccines
Background . A 23-valent unconjugated pneumococcal polysaccharide vaccine ( 23vP ) , routinely administered at the age of 65 , has limited effectiveness , and revaccination induces attenuated antibody responses . It is not known whether pneumococcal polysaccharide-protein conjugated vaccines ( PCV ) , although highly effective in infants , offer any immunological advantages over 23vP in adults . Methods . We immunized adults with schedules combining both PCV and 23vP  and investigated B-cell responses to establish whether PCV7 ( a 7-valent PCV ) induced T-dependent responses in adults , to assess the role of memory B cells in 23vP-induced antibody hyporesponsiveness , and to identify the B-cell subtypes involved . Results . A single dose of PCV7 induced significant increases in serotype-specific memory B-cell population s in peripheral blood indicating a T-dependent response . Conversely , immunization with 23vP result ed in a decrease in memory B-cell frequency . Furthermore , memory B-cell responses to subsequent immunization with PCV7 , when given after 23vP , were attenuated . Notably , B1b cells , a subset important in protecting mice against pneumococci , were also depleted following immunization with 23vP in humans . Conclusions . This study indicates that PCV7 may have an immunological advantage over 23vP in adults and that 23vP-induced depletion of memory and B1b-cell subsets may provide a basis for antibody hyporesponsiveness and the limited effectiveness of 23vP. Clinical Trials Registration . IS RCT N : 78768849 BACKGROUND Older adults are at high risk of developing invasive pneumococcal disease , but the optimal timing and number of vaccine doses needed to prevent disease among this group are unknown . We compared revaccination with 23-valent pneumococcal polysaccharide vaccine ( PN23 ) with primary vaccination for eliciting initial and persistent functional antibody responses . METHODS Subjects aged > or = 65 years were enrolled .  Functional ( opsonic ) and total immunoglobulin ( Ig ) G antibody levels were measured following either PN23 primary vaccination ( n = 60 ) or revaccination 3 - 5 years after receiving a first PN23 vaccination ( n = 60 ) . Antibody against vaccine serotypes 4 , 14 , and 23F was measured at prevaccination ( day 0 ) , 30 days after vaccination , and 5 years after vaccination . RESULTS By day 30 , both primary vaccination and revaccination induced significant increases in opsonic and IgG antibody levels . Day 30 levels following revaccination were slightly lower but not significantly different than those after primary vaccination . Year 5 levels were similar in both groups and remained significantly higher than prevaccination levels for primary vaccination subjects . There was good agreement between postvaccination opsonic and IgG antibody levels . CONCLUSIONS Revaccination of older adults with PN23 was comparable to primary vaccination for inducing elevated and persistent functional and IgG antibody responses CONTEXT Revaccination of healthy adults with pneumococcal polysaccharide vaccine ( PPV )  within several years of first vaccination has been associated with a higher than expected frequency and severity of local injection site reactions . The risk of adverse events associated with revaccination of elderly and chronically ill persons 5 or more years after first vaccination , as is currently recommended , has not been well defined . OBJECTIVE To determine whether revaccination with PPV at least 5 years after first vaccination is associated with more frequent or more serious adverse events than those following first vaccination . DESIGN Comparative intervention study conducted between April 1996 and August 1997 . PARTICIPANTS Persons aged 50 to 74 years either who had never been vaccinated with PPV ( n = 901 ) or who had been vaccinated once at least 5 years prior to enrollment ( n = 513 ) . INTERVENTION PPV vaccination . MAIN OUTCOME MEASURES Postvaccination local injection site reactions and prevaccination concentrations of type-specific antibodies . RESULTS Those who were revaccinated were more likely than those who received their first vaccinations to report a local injection site reaction of at least 10.2 cm ( 4 in ) in diameter within 2 days of vaccination : 11 % ( 55/513 ) vs 3 % ( 29/901 ) ( relative risk [ RR ] , 3.3 ; 95 % confidence interval [ CI ] , 2.1 - 5.1 ) . These reactions resolved by a median of 3 days following vaccination . The highest rate was among revaccinated patients who were immunocompetent and did not have chronic illness : 15 % ( 33/228 ) compared with 3 % ( 10/337 ) among comparable patients receiving their first vaccinations ( RR , 4.9 ; 95 % CI , 2.4 - 9.7 ) . The risk of these local reactions was significantly correlated with prevaccination geometric mean antibody concentrations . CONCLUSIONS Physicians and patients should be aware that self-limited local injection site reactions occur more frequently following revaccination compared with first vaccination ; however , this risk does not represent a contraindication to revaccination with PPV for recommended groups On August 13 , 2014 , the Advisory Committee on Immunization Practice s ( ACIP ) recommended routine use of 13-valent pneumococcal conjugate vaccine ( PCV13 [ Prevnar 13 , Wyeth Pharmaceuticals , Inc. , a subsidiary of Pfizer Inc. ] ) among adults aged ≥65 years .  PCV13 should be administered in series with the 23-valent pneumococcal polysaccharide vaccine ( PPSV23 [ Pneumovax23 , Merck & Co. , Inc. ] ) , the vaccine currently recommended for adults aged ≥65 years . PCV13 was approved by the Food and Drug Administration ( FDA ) in late 2011 for use among adults aged ≥50 years . In June 2014 , the results of a r and omized placebo-controlled trial evaluating efficacy of PCV13 for preventing community-acquired pneumonia among approximately 85,000 adults aged ≥65 years with no prior pneumococcal vaccination history ( CAPiTA trial ) became available and were presented to ACIP . The evidence supporting PCV13 vaccination of adults was evaluated using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) framework and determined to be type 2 ( moderate level of evidence ) ; the recommendation was categorized as a Category A recommendation . This report outlines the new recommendations for PCV13 use , provides guidance for use of PCV13 and PPSV23 among adults aged ≥65 years , and summarizes the evidence considered by ACIP to make this recommendation BACKGROUND The benefits of using the 23-valent pneumococcal polysaccharide vaccine ( PPV23 ) are controversial . This study assessed clinical effectiveness of PPV23 in preventing community-acquired pneumonia ( CAP ) among the general population aged ≥ 60 years . METHODS This was a population -based cohort study involving 27 204 individuals aged ≥ 60 years in Tarragona , Spain , who were prospect ively followed from 1 December 2008 until 30 November 2011 . Primary outcomes were hospitalization for pneumococcal CAP ( bacteremic and nonbacteremic cases ) and all-cause CAP . All CAP cases were radiographically confirmed and vali date d by checking clinical records . Cox regression was used to evaluate the association between pneumococcal vaccination and the risk of each outcome . RESULTS Cohort members were followed for a total of 76 033 person-years ( 29 065 person-years for vaccinated subjects ) . Incidence rates ( per 1000 person-years ) were 0.21 for bacteremic pneumococcal CAP ( 0.14 vs 0.26 among vaccinated and unvaccinated subjects , respectively ) , 1.45 for nonbacteremic pneumococcal CAP ( 1.46 vs 1.44 ) , and 7.51 for all-cause CAP ( 7.19 vs 7.71 ) . In primary analyses including all cohort members , PPV23 did not appear to be effective against any analyzed outcome . However , a beneficial effect emerged in sensitive and stratified analyses . After multivariable adjustments , as compared with those never vaccinated , recent vaccination with PPV23 ( < 5 years ago ) was associated with reduced risks of bacteremic pneumococcal CAP ( hazard ratio [ HR ] , 0.38 ; 95 % confidence interval [ CI ] , .09 - 1.68 ) , nonbacteremic pneumococcal CAP ( HR , 0.52 ; 95 % CI , .29-.92 ) , overall pneumococcal CAP ( HR , 0.49 ; 95 % CI , .29-.84 ) , and all-cause CAP ( HR , 0.75 ; 95 % CI , .58-.98 ) . CONCLUSIONS Our data support a protective effect of recent PPV23 vaccination ( within previous 5 years ) against both pneumococcal and all-cause CAP Renal transplant recipients are at increased risk of developing invasive pneumococcal diseases but may have poor response to the 23-valent pneumococcal polysaccharide vaccine ( PPV ) . It may be possible to enhance immunogenicity by priming with 7-valent pneumococcal conjugate vaccine ( 7vPnC ) and boosting with PPV 1 year later . In a r and omized single-blind , controlled study , adult recipients of renal transplants received either 7nPVC or PPV followed by PPV 1 year later . The vaccine response was defined as 2-fold increase in antibody concentration from baseline and an absolute post-vaccination values ≥1 µg/ml . The primary endpoint was vaccine response of the primed group ( 7vPnC/PPV ) compared with single PPV vaccination . Antibody concentrations for 10 serotypes were measured at baseline , 8 weeks after first vaccination , before second vaccination , and 8 weeks after second vaccination . Of 320 screened patients , 80 patients were r and omized and 62 completed the study . Revaccination with PPV achieved no significant increase of immune response in the 7vPnC/PPV group compared with the single PPV  recipients A response to at least 1 serotype was seen in 77.1 % of patients who received 7vPnC and 93.1 % of patients who received PPV ( P = 0.046 ) . After second vaccination response to at least 1 serotype was seen in 87.5 % patients of 7vPnC/PPV group and 87.1 % patients of PPV group ( non significant p ) . The median number of serotypes eliciting a response was 3.5 ( 95 % CI 2.5–4.5 ) in the 7vPnC/PPV group versus 5 ( 95 % CI 3.9–6.1 ) in the PPV group ( non-significant p ) . Immunogenicity of pneumococcal vaccination was not enhanced by the prime – boost strategy compared with vaccination with PPV alone . Administration of a single dose of PPV should continue to be the st and ard of care for adult recipients of renal transplants . Trial Registration EudraCT 2007 - 004590 - 25 BACKGROUND Following vaccination with 23-valent pneumococcal polysaccharide vaccine ( PPV ) , pneumococcal antibody levels decline to prevaccination levels within 6 - 10 years . The Advisory Committee on Immunization Practice s does not recommend routine revaccination because data on the safety and effectiveness of additional doses are insufficient . METHODS To determine whether medically attended adverse events occur more frequently after the third dose of PPV than after the first or second dose , we performed a retrospective review of medical records from a computer data base for health care facilities that serve more than one-half of the Alaska Native population . All persons who had received > or = 3 PPV doses ( n = 179 ) were included in the review , as were a r and omly selected comparison group of 181 persons who had received 1 or 2 doses . RESULTS Only 1 ( 0.55 % ) of 179 persons who had received > or = 3 PPV doses and 4 ( 2.76 % ) of 181 persons in the comparison group had a medically attended adverse event , and no severe adverse events were recorded . CONCLUSION We found no difference in the risk of medically attended adverse events following > or = 3 doses of PPV , compared with 1 or 2 doses BACKGROUND Unlike free polysaccharide vaccines , pneumococcal polysaccharide conjugate vaccines ( PCVs ) induce a T cell-dependent immune response and have the potential to provide an extended duration of protection with repeated vaccinations . METHODS This was an extension of a previous study in pneumococcal  vaccine-naïve adults aged 50 - 64 years in which adults 60 - 64 years of age were given 13-valent PCV ( PCV13 ) or 23-valent pneumococcal polysaccharide vaccine ( PPSV23 ) and adults aged 50 - 59 were given PCV13 . In this follow up study conducted about 4 years later , the 60 - 64 year olds initially given PCV13 received PCV13 or PPSV23 , and those initially given PPSV23 received another PPSV23 . All adults aged 50 - 59 years were re-vaccinated with PCV13 .  Anti-pneumococcal opsonophagocytic activity ( OPA ) titers were measured before and 1 month after vaccination . RESULTS A second PCV13 given about 4 years after a first vaccination induced OPA titers that were significantly higher than those following the initial vaccination for 7 of 13 serotypes in the older group , and 6 of 13 serotypes in the younger group , and responses to the remaining serotypes were largely non-inferior . In contrast , OPA titers following revaccination with PPSV23 were statistically significantly lower for 9 of the 13 serotypes , and non-inferior for the remaining serotypes , when compared to the responses to the first PPSV23 . OPA titers in the older adults who received PPSV23 after initial PCV13 were significantly higher than those following a first PPSV23 for 10 of the 13 serotypes . CONCLUSION In adults 50 to 64 years of age , initial vaccination with PCV13 establishes an immune state that results in recall anti-pneumococcal responses upon subsequent vaccination with either conjugated or free polysaccharide vaccine . In contrast , initial vaccination with PPSV23 results in an immune state in which subsequent PPSV23 administration yields generally lower responses compared with the initial responses Infant 13-valent pneumococcal conjugate vaccination ( PCV13 ) was introduced to the UK in 2010 . Its impact on serotypes implicated in adult non-bacteraemic pneumococcal pneumonia is not known . Beginning in 2008 , a 5-year prospect i ve cohort study of adults admitted to hospital with community-acquired pneumonia ( CAP ) was conducted . Pneumococcal serotype was established using a vali date d multiplex immunoassay ( Bio-Plex ; Bio-Rad , Hercules , CA , USA ) . The overall incidence for hospitalised CAP and pneumococcal CAP was 79.9 ( 95 % CI 76.6–83.3 ) and 23.4 ( 95 % CI 21.6–25.3 ) per 100 000 population , respectively . A decline in CAP ( incidence rate ratio ( IRR ) per year 0.96 , 95 % CI 0.94–0.99 ; p=0.016 ) and pneumococcal CAP ( IRR per year 0.84 , 95 % CI 0.80–0.89 ; p<0.001 ) was observed over the 5-year period of the study . Between the pre- and post-PCV13 periods of the study , the incidence of CAP due to serotypes included in the PCV7 declined by 88 % ( IRR 0.12 , 95 % CI 0.08–0.20 ; p<0.001 ) , and CAP due to the additional 6 serotypes in PCV13 declined by 30 % ( IRR 0.70 , 95 % CI 0.51–0.96 ; p=0.024 ) . Incidence of adult pneumococcal pneumonia declined over the last 5 years , with serotypes included in PCV13 declining post-PCV13 introduction , indicating early herd protection effects from PCV13 infant vaccination on adult non-bacteraemic disease . These effects may accrue over the coming years with implication s for national pneumococcal vaccination policies in adults . This is the first study to indicate herd protection from infant PCV13 on adult non-bacteraemic pneumococcal pneumonia BACKGROUND Although the 23-valent pneumococcal polysaccharide vaccine ( PPSV23 ) protects against invasive disease in young healthy persons , r and omized controlled trials in chronic obstructive pulmonary disease ( COPD ) have demonstrated no benefit in the intention-to-treat population . We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine ( PCV7 ) is safe and induced greater serotype-specific immunoglobulin G ( IgG ) and functional antibody than did PPSV23 1 month after vaccination . We hypothesized that these advantages would persist at 1 and 2 years . METHODS One hundred eighty-one patients with moderate to severe COPD were r and omized to receive PPSV23 ( n = 90 ) or PCV7 ( 1.0 mL ; n = 91 ) . We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a st and ardized opsonophagocytosis assay , reported as a killing index ( OPK ) . We determined differences in IgG and OPK between vaccine groups at 1 and 2 years . RESULTS Relative to PPSV23 , PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes ( not 19F ) . This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years . Comparable differences in IgG were observed but were less often statistically significant . Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration , almost 50 % of individuals had never been vaccinated . No differences in the frequency of acute exacerbations , pneumonia , or hospitalization were observed . CONCLUSIONS PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination . This superior functional response supports testing of conjugate vaccination in studies examining clinical end points . CLINICAL TRIALS REGISTRATION NCT00457977 In a study of older adults , first and second doses of 23-valent pneumococcal polysaccharide vaccine ( PN23 ) induced IgG increases for all 8 vaccine serotypes tested . Participants ( N=143 , mean age 76 years ) were re-enrolled to study antibody levels after ten years , and safety and immunogenicity of another PN23 dose . Ten years after first or second doses , mean IgG concentrations exceeded vaccine-naïve levels for 7 of 8 serotypes tested . Second and third doses administered at this time were generally well tolerated and were immunogenic , inducing similar postvaccination levels . Immunogenicity is preserved after multiple PN23 doses without evidence of a lower than expected immune response ( i.e. , without hyporesponsiveness ) Revaccination with the 23-valent pneumococcal polysaccharide vaccine ( PPV ) has remained controversial due to lack of immunological data and fear of side effects . We re-vaccinated 61 elderly patients ( median age 75 years ) , who had a history of hospital treatment for pneumonia , with PPV on average 5.3 years after their primary vaccination . Revaccination result ed in significant increases of the geometric mean antibody concentration ( GMC ) and the geometric mean antibody fold increase ( GMFI ) , although to lower levels than after primary vaccination . 36/61 ( 59 % ) of the patients responded with a GMFI of > or = 2 to > or = 2 of six serotypes . Local reactions to revaccination were common ( 63 % ) , but mild , and there were no serious adverse events . We conclude that revaccination of elderly with PPV after 5 - 10 years is safe and induce a significant immune response in a majority of persons The best method of evaluating the efficacy of a vaccine is to compare the incidence of the disease against which it is prepared in r and omized , placebo-controlled clinical trials involving vaccinated and unvaccinated subjects . In the case of Streptococcus pneumoniae , the proposed alternatives are evaluations of the so-called “ correlates of protection ” ( i.e. markers of the vaccine-induced immune response that predict protection from infection and disease ) and nasopharyngeal carriage . The aim of this paper is to discuss the most important limitations of the immunological criteria suggested for licensing new pneumococcal vaccines , and comment on the use of carriage as an endpoint for evaluating efficacy . Data showed why the use of a single serological correlate of protection can not be considered the best means of evaluating pneumococcal vaccines and highlighted the importance of using carriage for efficacy evaluation but in the meantime the need to develop new sensitive and specific methods
Background In many industrialized countries routine vaccination with the 23-valent pneumococcal polysaccharide vaccine ( PPSV-23 ) is recommended to prevent pneumococcal disease in the elderly .
However , vaccine-induced immunity wanes after a few years , and there are controversies around revaccination with PPSV-23 .
Here , we systematic ally assessed the effectiveness and safety of PPSV-23 revaccination .