A search for serologic correlates of immunity to Bordetella pertussis cough illnesses. A clinical trial of a monocomponent pertussis toxoid vaccine. Levels of anti-pertussis antibodies related to protection after household exposure to Bordetella pertussis. DEVELOPMENT OF A PERTUSSIS COMPONENT VACCINE IN JAPAN Acellular pertussis vaccines. Efficacy and evaluation of clinical case definitions. Antibody and cell-mediated immune responses to booster immunization with a new acellular pertussis vaccine in school children.
In a  pertussis vaccine efficacy trial in Germany we collected sera from vaccinees ( DTaP or DTP ) after the third and fourth doses of vaccine or at comparable time periods in DT vaccine recipients . In addition , sera were collected from a r and omized sample of subjects in each vaccine group at approximately 3-month intervals from which antibody kinetic curves were constructed , which allowed us to estimate specific antibody values to pertussis toxin ( PT ) , filamentous hemagglutinin ( FHA ) , pertactin and fimbriae-2 at the time of exposure in the household setting . The imputed geometric mean antibody values to PT , pertactin and fimbriae-2 at the time of household exposure to Bordetella pertussis infection were higher ( p < 0.07 or lower ) in non-cases compared with cases . A multivariate ( classification tree ) analysis found that only pertactin and PT were significant in protection . Subjects with an imputed pertactin value of < 7 EU ml-1 had a 67 % ( 18/27 ) chance of infection regardless of the PT value . If the pertactin value was > or = 7 EU ml-1 and the PT value > or = 66 EU ml-1 all subjects were non-cases . If the pertactin value was > or = 7 and the PT value was < 66 EU ml-1 the predicted probability of being a case was 31 % ( 15/49 ) . Logistic regression analysis also found that high versus low pertactin values were associated with illness prevention following household exposure . In the presence of antibody to pertactin , PT and fimbriae-2 , the additional presence of antibody to FHA did not contribute to protection . Our data support historical data indicating that agglutinating antibodies are associated with protection and also recent serologic correlates data and clinical efficacy data which indicate that multicomponent vaccines containing pertactin and fimbriae have better efficacy than PT or PT/FHA vaccines We compared a monocomponent pertussis toxoid vaccine preparation ( JNIH-7 ) in a double-blind , r and omized study with another component vaccine ( JNIH-6 ) containing pertussis toxoid and filamentous hemagglutinin in equal proportions . Monocomponent pertussis toxoid vaccines have not been tested previously in children . This trial comprised 255 previously nonimmunized children 6 to 10 months old who were given two 0.5-mL subcutaneous injections of either vaccine four to five weeks apart . Prevaccination and postvaccination serum sample s from 235 infants showed an antitoxin seroconversion rate of 100 % in both groups . Adverse reactions were few and mild , with local reactions occurring more often after administration of the second dose and among recipients of the two-component vaccine ( P less than .05 ) Vaccine efficacies against typical pertussis after household exposure to Bordetella pertussis were estimated to be 75.4 % for an acellular five-component vaccine , 42.4 % for an acellular two-component vaccine , and 28.5 % , for a licensed US whole cell vaccine , compared to placebo . Logistic regression analyses demonstrated statistically significant correlations between clinical protection and the presence of IgG antibodies against pertactin , fimbriae 2/3 and pertussis toxin in pre-exposure sera . Multicomponent pertussis vaccines of proven high efficacy in recent Swedish NIAID-sponsored efficacy trials induced higher antibody levels against pertactin and fimbriae 2/3 than less efficacious vaccines . Anti-pertactin , anti-fimbriae 2/3 , and anti-PT may be used as surrogate markers of protection for multicomponent acellular and whole-cell vaccines against pertussis Antibodies against two physicochemically purified haemagglutinins ( HAs ) of Bordetella pertussis ( filamentous HA and leucocytosis-promoting-factor HA ) protect laboratory animals from pertussis . A vaccine containing these two HAs was prepared and tested in trials involving about 5000 children . Culture supernatant of Bordetella pertussis , phase I , was treated with ammonium sulphate , and a crude extract of the HAs was extracted from the precipitate by the use of concentrated sodium chloride . This crude extract was fractionated by sucrose density gradient centrifugation to obtain an HA preparation practically free of endotoxin . The HA preparation was treated with formalin to destroy its ability to induce leucocytosis and to cause histamine sensitisation . Aluminium hydroxide was added to the preparation as an adjuvant . The component vaccine is not only potent as judged by the mouse test but is also less than one-tenth as toxic as whole-cell vaccine as judged by leucocytosis promotion , histamine sensitisation , and endotoxicity tests . Field trials showed that component vaccine was as effective as and produced less side-effects than did conventional whole-cell vaccine . The vaccine has been used for mass immunisation in Japan since the autumn of 1981 The efficacy of two acellular pertussis vaccines was estimated for various clinical case definitions , with and without the requirement of culture confirmation , from a r and omized trial in Sweden .  Efficacy increased with duration of coughing spasms and when the case definition included whoops or whoops plus at least nine coughing spasms a day . After deletion of clinical cases not believed to be caused by pertussis , efficacies were closer to the higher values for culture-confirmed disease . Nonspecificity of the clinical criterion " 21 days of coughing spasms with whoops " result ed in estimates of predictive value for pertussis of 85 % for placebo recipients and 56 % for vaccinees . We conclude that laboratory confirmation of suspected cases is needed in pertussis vaccine trials . A suggested case definition is 21 days or more of coughing spasms with confirmation by culture , serologic study , or household exposure to culture-confirmed pertussis 235 healthy 10 - 12 years old school children were r and omly immunized with either a booster dose of diphtheria-tetanus-acellular pertussis ( dTap ) or diphtheria-tetanus ( dT ) vaccine . For this booster immunization design ed for school children and adults , the quantities of Bordetella pertussis antigens in the dTap vaccine had been reduced to one third of those of the Infanrix vaccine ( SmithKline Beecham ) commonly used for infants . IgG antibodies and cell-mediated immune ( CMI ) responses to pertussis toxin ( PT ) , pertactin ( PRN ) and filamentous hemagglutinin ( FHA ) were assessed by an enzyme immunosorbent assay and in vitro proliferation of peripheral blood mononuclear cells , respectively . Before immunization , 55 % , 80 % and 99 % of children had detectable serum IgG antibodies to PT , PRN and FHA , whereas CMI response was found in 35 % , 27 % and 50 % of children , respectively . After immunization , a 20 - 30-fold increase in geometric mean level ( GML ) of antibodies to the pertussis antigens occurred and CMI response to PT , PRN and FHA was seen in 88 % , 94 % and 100 % of children , respectively . Adverse reactions following the immunization were rare . The results show that booster immunization with an acellular pertussis vaccine with reduced concentrations of antigens induces both antibody and CMI responses and support further studies of this pertussis vaccine in school children
BACKGROUND Routine use of whole-cell pertussis ( wP ) vaccines was suspended in some countries in the 1970s and 1980s because of concerns about adverse effects .
Following such action , there was a resurgence of whooping cough .
Acellular pertussis ( aP ) vaccines , containing purified or recombinant Bordetella pertussis ( B. pertussis ) antigens , were developed in the hope that they would be as effective , but less reactogenic than the whole-cell vaccines .
OBJECTIVES To assess the efficacy and safety of acellular pertussis vaccines in children .