Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the Italian Pertussis Vaccine Trial, data were collected to evaluate the persistence of anti-pertussis antibodies. A sub-cohort of 1275 children was followed for this purpose until a mean age of 21 months. An additional evaluation included pooled cross-sectional analysis of serum specimens collected for analysis of cough illnesses. Antibodies to PT, FHA and PRN were measured by ELISA using a standardized technique. With both acellular vaccines in the study (the Chiron Biocine three-component and SmithKline Beecham three-component vaccines) there was a fast and steep decrease of mean geometric titres for PT, FHA and PRN in the months immediately following vaccination. Titres were close to the detection limit 15 months after the end of primary immunization. The immunogenicity of the whole-cell study vaccine (produced by Connaught Laboratories, Inc. Swiftwater, USA) was poor as determined one month after the third dose and no antibody was detected in nearly all children 15 months after the end of vaccination.
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PMID:Antibody kinetics and long-term sero-prevalence in the Italian clinical trial of acellular pertussis vaccines. 927 60

In an investigation of cell-mediated immunity against Bordetella pertussis, we found that B. pertussis infection in infants and in mice was associated with the induction of antigen-specific T cells that secrete IFN-g and IL-2, but not IL-4 or IL-5. This cytokine profile is characteristic of Th1 cells that mediate cellular immune responses against a range of intracellular pathogens. An examination of cytokine production following immunization with a three-component acellular vaccine, comprising inactive PT, FHA and pertactin adsorbed to alum, demonstrated that spleen cells from vaccinated mice produced high levels of IL-5, but no detectable IFN-g and low levels of IL-2. In contrast, peripheral blood mononuclear cells from vaccinated infants produced IL-2, IL-5 and IFN-g. These findings highlight significant differences in the immune responses generated by vaccination and natural infection with B. pertussis and demonstrate that the T-cell response induced with an acellular vaccine, although dominated by type 2 cytokines in mice, is more heterogeneous in infants with a Th0 or mixed Th1/Th2 cytokine profile.
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PMID:Bordetella pertussis-specific Th1/Th2 cells generated following respiratory infection or immunization with an acellular vaccine: comparison of the T cell cytokine profiles in infants and mice. 927 63

The induction of cell-mediated immunity (CMI) to Bordetella pertussis antigens (whole, heat-inactivated bacterial cells [BPC], pertussis toxin [PT], filamentous haemagglutinin [FHA], pertactin [PRN]) was assessed by a lymphoproliferation assay in vitro in a cohort of children enrolled in a randomized clinical trial of pertussis vaccines efficacy in Italy. Four vaccination groups were compared: children receiving acellular pertussis (aP) vaccines from SmithKline Beecham (SB) or Chiron Biocine (CB) or whole-cell vaccine (wP) from Connaught, each combined with diphtheria and tetanus toxoids (DT), or a DT vaccine only. When the purified antigens were used, statistically significant differences in CMI responses were observed between pre- and post-vaccination samples. In particular, CMI responses to FHA and PRN were detected in the majority of both aP vaccines recipients, whereas DTwP-recipients were CMI-positive in a much lower proportion. Clear-cut differences in PT responses were detected between DTwP and DTaP vaccine recipients, in favour of the latter. These differences were maintained up to 24 months after completion of the primary vaccination schedule. Thus, CMI responses could be a useful adjunct to serology in studying the immune responses to pertussis vaccines.
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PMID:Acellular vaccines induce cell-mediated immunity to Bordetella pertussis antigens in infants undergoing primary vaccination against pertussis. 927 65

Recent epidemiologic data have indicated that adults are the most important reservoir that transmit pertussis to children. However, conventional whole cell pertussis vaccine is contraindicated in adults and children over 7 years of age because of the unacceptably high rate of adverse reactions. The aim of this study is to evaluate the specific cellular immune responses and adverse reactions to a less reactogenic acellular pertussis vaccine in adult volunteers. Eighty healthy medical personnel in Chang Gung Children's Hospital were enrolled. Volunteers in each group received: (1) Td + full strength acellular pertussis vaccine (PT, 1 microgram/0.5 ml; FHA, 4 micrograms/0.5 ml); (2) Td + half strength acellular pertussis vaccine; (3) Td alone. Lymphocyte phenotypic analysis, antigen-specific antibody titers, antigen-specific proliferative response and cytokine levels were evaluated before and 1 month after vaccination. Our data revealed: (1) the adverse reactions were minimal; (2) phenotypic analysis showed no non-specific activation of helper T or memory T cell after vaccination; (3) both PT and FHA-specific antibody titers increased significantly after vaccination, (4) PT antigens had a mitogenic effect on cord blood mononuclear cells and peripheral blood mononuclear cells of the adult volunteers; (5) FHA-specific T cell proliferative responses significantly increased after vaccination; (6) the cytokine production pattern showed predominant activation of Th 1 cells as reflected in increased production of gamma-IFN after vaccination. Acellular pertussis vaccine can effectively induce both humoral and cellular immune response in adults.
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PMID:Specific immune response in adult medical personnel immunized with acellular pertussis vaccine with special emphasis on T helper cell response. 941 2

Pertussis vaccinations are administered worldwide under various conditions and schedules with diphtheria-tetanus-pertussis (DTP). In Japan, a general vaccination with three primary doses of diphtheria-tetanus-acellular pertussis (DTaP) at 4-week intervals and one booster dose 12 months after the primary series have been used since 1981. Decreasing the number of doses of the vaccination would lessen the physical and economic costs. To compare the immunological response to two versus three primary doses, we assessed antibody and cellular immune responses in health children. The anti-filamentous hemagglutinin (anti-FHA) and anti-pertussis toxin (anti-PT) antibody responses to two primary doses of DTaP before a booster were significantly lower than the responses to three primary doses. Although these antibody levels were low in children who received two primary doses, the FHA-induced DNA synthesis was equal to that of the children who received three doses. The anti-FHA and anti-PT antibody levels 4 weeks after the booster following two doses were similar to the levels following three doses, and high antibody titers were maintained over a long period. In areas where contact with bacteria is expected, two primary doses of DTaP may be adequate to induce the necessary level of immunological responses.
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PMID:Two primary doses of diphtheria-tetanus-acellular pertussis vaccine induce immunological responses to Bordetella pertussis as strong as those induced by three primary doses. 941 7

Due to local and systemic side-effects, the currently used, highly effective, whole-cell pertussis vaccines (WCVs) will be replaced by acellular vaccines (ACVs) in some countries. These ACVs contain detoxified pertussis toxin, either alone or in combination with the filamentous haemagglutinin, pertactin and fimbriae. Ongoing clinical trials show that ACVs are clearly less reactogenic than WCVs and that ACVs comprised of three to five proteins are highly efficacious in inducing protection against Bordetella pertussis infections. An important unresolved question is, what the effect will be of the switch from WCVs to ACVs on the incidence of Bordetella parapertussis infections, the second causative agent of pertussis. A comparison of the efficacy of WCVs and ACVs against B. parapertussis infection is required to answer this question. We show that the Dutch WCV, although prepared from B. pertussis strains, protects against B. parapertussis infection in a murine respiratory model, although less efficiently than against B. pertussis infection. It was shown previously that the ACV components pertussis toxin, FHA and pertactin did not protect against B. parapertussis infection in a murine respiratory model. We have investigated the efficacy of two other ACV components, B. pertussis serotype-2 and -3 fimbriae against B. parapertussis infection in the murine model. The B. pertussis fimbriae protected mice against B. parapertussis infection although less efficiently than against B. pertussis infection. This result indicates that B. pertussis and B. parapertussis fimbriae are antigenically distinct. B. pertussis fimbriae were found to be as efficacious as the WCV against B. pertussis infection. Our results are discussed in the light of the switch from WCVs to ACVs.
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PMID:The efficacy of a whole cell pertussis vaccine and fimbriae against Bordetella pertussis and Bordetella parapertussis infections in a respiratory mouse model. 968 86

Serum resistance, or resistance to killing by antibody dependent pathway of complement, in Bordetella pertussis is bvg-regulated and the Bordetella resistance to killing (brk) locus mediates much of the resistance. Here we examined whether other bvg-regulated proteins contribute to serum resistance. We found that neither pertussis toxin, adenylate cyclase toxin, filamentous hemagglutinin, dermonecrotic toxin, tracheal colonization factor, nor Vag8 mutants were sensitive to serum killing compared to the wild-type. Filamentous hemagglutinin has been reported to bind C4 binding protein, an inhibitor of complement, but this activity does not appear to contribute to serum resistance, as evidenced by the resistant phenotype of FHA mutants. Clinical isolates were serum resistant and wild-type strains possessing an additional copy of the brk locus were 2-5-fold more resistant to serum killing.
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PMID:Serum resistance in bvg-regulated mutants of Bordetella pertussis. 963 46

Cell-mediated immune (CMI) responses to Bordetella pertussis antigens (pertussis toxin [PT], pertactin [PRN], and filamentous hemagglutinin [FHA]) were assessed in 48-month-old recipients of acellular pertussis [aP] vaccines (either from Chiron-Biocine [aP-CB] or from SmithKline Beecham [aP-SB]) and compared to CMI responses to the same antigens at 7 months of age, i.e., 1 month after completion of the primary immunization cycle. None of the children enrolled in this study received any booster of pertussis vaccines or was affected by pertussis during the whole follow-up period. Overall, around 75% of 4-year-old children showed a CMI-positive response to at least one B. pertussis antigen, independently of the type of aP vaccine received, and the proportion of CMI responders were at least equal at 48 and 7 months of age. However, longitudinal examination of individual responses showed that from 20 (against PT) to 37% (against FHA) of CMI responders after primary immunization became negative at 48 months of age. This loss was more than compensated for by conversion to positive CMI responses, ranging from 36% against FHA to 69% against PRN, in other children who were CMI negative at 7 months of age. In 60 to 80% of these CMI converters, a lack of decline or even marked elevation of antibody (Ab) titers against B. pertussis antigens also occurred between 20 and 48 months of age. In particular, the frequency of seropositivity to PRN and FHA (but not to PT) was roughly three times higher in CMI converters than in nonconverters. The acquisition of CMI response to B. pertussis antigens in 48-month-old children was not associated with a greater frequency of coughing episodes lasting >/=7 days and was characterized by a prevalent type 1 cytokine profile, with high gamma interferon and low or no production of interleukin-5, reminiscent of cytokine patterns following immunization with whole-cell pertussis vaccine or natural infection. Our data imply that vaccination-induced systemic CMI may wane by 4 years of age but may be acquired or naturally boosted by symptomless or minor clinical infection by B. pertussis. This might explain, at least in part, the persistence of protection against typical pertussis in aP vaccine recipients despite a substantial waning of both Ab and CMI responses induced by the primary immunization.
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PMID:Cell-mediated immune responses in four-year-old children after primary immunization with acellular pertussis vaccines. 1041 75

Since the development and introduction of the acellular pertussis vaccine in Japan in the early eighties, we have come a long way in using this component in combination with other vaccines. However, the basic problem in development of an effective and safe pertussis vaccine is that the antigens to induce complete protection against clinical pertussis and the precise mechanism by which pertussis vaccine confers immunity is yet unknown. Hence, the composition of future acellular pertussis vaccine remains an open issue. Recently, acellular pertussis vaccine has been licensed for the booster doses in the U.S.A. and for primary immunization of infants in Italy and Germany. A multicentric trial has been carried out to compare the serological response and adverse reactions of 13 acellular pertussis vaccines. These vaccines contained one or more of the four components, i.e. FHA, PT, 69 kDa OMP and fimbriae. All vaccines were associated with substantially fewer and less adverse reactions and were more immunogenic with respect to antibodies against the added antigens. DTP vaccines in the near future will have combinations of other components and the key antigen for combination will be acellular pertussis component which is going to replace whole cell pertussis component in DTP vaccines. In view of this, manufacturers like ourselves from the developing countries are still groping in the dark, uncertain whether we should have a single component acellular pertussis vaccine or multicomponent one. This will have a major impact on the cost of production, the final cost of the combination vaccines and the regulatory issues that we will have to tackle in view of the recent thinking on harmonization in the pharmaceutical industry.
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PMID:Composition of acellular pertussis and combination vaccines: a general review. 1060 Jan 95

Vaccines containing acellular pertussis components, either separate or combined with other microbial antigens, were evaluated for specific immune responses in guinea-pigs and mice. The capacity of sera to protect chick embryos from the lethal effect of pertussis toxin was independent of the Chinese hamster ovary cell clumping neutralization titre and the antigen binding ELISA anti-toxin titre. Direct correlations did not exist between ELISA titres to Pt, FHA, fimbria or 69 kDa and capacity to prevent killing of embryos by different strains of Bordetella pertussis. With the exception of one combination vaccine product, addition of foreign microbial antigens to acellular pertussis vaccines did not significantly alter capacity of the sera to protect embryos against toxin or bacteria.
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PMID:Acellular pertussis vaccines: neutralization by immune sera of the lethality of pertussis toxin and viable Bordetella pertussis for chick embryos. 1060 Feb 3


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