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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first efficacy trial of pertussis vaccines with defined purified antigens failed to demonstrate a serologic correlate of protection, although both tested vaccines were shown to give significant protection against typical whooping cough. The antibody response to pertussis toxoid was dose dependent. A lower anti-PT response in the two-component vaccine, containing one-half the amount of PT in the one-component vaccine, seemed to be compensated by a significant anti-FHA response, since both vaccines conferred similar protection against typical illness. However, the immunologic mechanisms whereby protection is conferred remain unclear. At present antibody responses to the antigens included in the first tested vaccines could be used as pseudoindicators of protection. The group of vaccinated infants who were protected did differ in their antibody profile as compared to unvaccinated infants. Tentatively, candidate vaccines should elicit no less antibody responses to PT and FHA as those elicited by the above one- and two-component vaccines, respectively. The response to other antigens such as pertactin and fimbriae cannot be related to protection at present. Ongoing efficacy trials of a number of pertussis vaccines of varying composition may or may not provide immunological correlates of protection against pertussis. The trials ought to be subjected to a preplanned, independent (meta)analysis with defined end points to increase the understanding of the contribution of various antigens to the protective efficacy of pertussis vaccines.
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PMID:Defining surrogate serologic tests with respect to predicting protective vaccine efficacy: pertussis vaccination. 762 63

The chromosome of Bordetella pertussis harbours a region of 27 contiguous kb, which contains the bvg, fha and fim genes, involved in the co-ordinate regulation of virulence genes, FHA production and fimbriae production, respectively. The linkage of FHA and fimbrial genes has resulted in some confusion concerning the existence and location of genes required for the production of FHA and the function of the fimbrial genes fimB-D, which were proposed to be involved in both FHA and fimbriae biosynthesis. Through the use of non-polar mutations in each of these genes, we found that fimB-D are required for the production of both serotype 2 and 3 fimbriae, but not for FHA biosynthesis. Furthermore, a large open reading frame, designated fhaC, was identified downstream of fimD. It was shown that fhaC is essential for FHA production but not for fimbriae biogenesis. We propose that insertion mutations in fimB-D affect FHA production because of polar effects on fhaC expression. An insertion in the region downstream of fhaC had only a slight effect on FHA and fimbriae production. The fhaC gene product shows homology with ShIB and HpmB, two outer membrane proteins involved in export and activation of the haemolysins, ShIA and HpmA, of Serratia marcescens and Proteus mirabilis, respectively. Homology is also observed between the N-termini of FHA, ShIA and HpmA. Export of the haemolysins requires the N-termini of these molecules, and when this region was removed from FHA by an in-frame deletion, FHA biosynthesis was abolished. These results suggest that the N-terminus of FHA interacts with FhaC, and that as a result FHA is transported across the outer membrane.
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PMID:Mutational analysis of the Bordetella pertussis fim/fha gene cluster: identification of a gene with sequence similarities to haemolysin accessory genes involved in export of FHA. 817 Mar 96

An observation on immunization reaction and serological effect of adsorbed purified pertussis vaccine for the first time in China had been carried out in Zhengzhou. Phase I field trial had been conducted in 8 adults and 20 children in whom there was no local reaction and temperature reaction in adults and only mild temperature reaction (37.6 degrees C-38 degrees C) in 4 children. Phase II field trial showed that the adsorbed purified pertussis vaccine manifested trivial reaction, none developed severe temperature reaction (39.1 degrees C), and 8 person-times of moderate temperature reaction (38.1 degrees C-39.1 degrees C) occurred in 100 children after 3 doses. Whereas 2 person-times of severe reaction and 39 person-times of mild reaction occurred in 101 children after receiving the whole cell pertussis vaccine. None showed local severe reaction (5.1 cm) and 1 person-time of mild local reaction appeared at 48 hours after each of 3 doses of adsorbed purified pertussis vaccine (102, 102, 98 children, respectively); Whereas, 3 person-times of severe local reaction and 17 person-times of mild local reaction occurred after each of 3 doses of whole cell pertussis vaccine (97, 100, 97 children, respectively). Satisfactory immunogenicity of the adsorbed purified pertussis vaccine was confirmed. The high serum hemagglutinin titer was achieved in 90 children, the GMT reached 817 (9.16 for preimmunization), and titers reaching 1:320 and over (a level protecting human from being infected) accounted for 84.4 percent. The average levels of anti-LPF and anti-FHA antibodies in 60 and 53 persons attained to 24.17 +/- 3.9421 EU/ml and 38.85 +/- 7.2466 EU/ml, respectively.
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PMID:[An observation on immunization reaction and serological effect of adsorbed purified pertussis vaccine]. 822 38

Two acellular pertussis vaccines, one containing only LPF toxoid (25 micrograms) and the other containing LPF toxoid (25 micrograms) and FHA (25 micrograms) and each combined with diphtheria and tetanus toxoids, were evaluated in two groups of 25 infants. A third group of 25 infants served as controls and received a DTP whole-cell pertussis vaccine. Infants given either acellular pertussis vaccine had significantly fewer local and systemic reactions than infants given whole-cell vaccine. Among the three vaccine groups, infants given the LPF vaccine (single component) had the highest concentration of antibody to LPF after three immunizations. Infants receiving the LPF/FHA vaccine (two-component) had the highest concentration of antibody to FHA after three immunizations. Infants vaccinated with the two-component vaccine had a significantly lower serological response to LPF than infants given the single component vaccine, as measured by either enzyme-linked immunosorbent assay or CHO cell assay. Further studies are necessary to determine why differences in immunogenicity of the two investigational vaccines occurred.
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PMID:Acellular pertussis vaccines in infants: evaluation of single component and two-component products. 830 37

Intranasal immunization of adult female Balb/c mice with the Bordetella pertussis antigens FHA or P.69, greatly enhanced their ability to clear B. pertussis from their lungs following aerosol challenge compared with ovalbumin-immunized controls. Low numbers of lymphocytes secreting antibodies (IgG, IgA and IgM) against the immunizing antigens could be isolated from the lungs of immunized mice. Following aerosol challenge with B. pertussis there was a large increase in the numbers of FHA or P.69-specific antibody-secreting cells in the lungs of mice immunized with these antigens. Intranasal immunization, particularly with FHA, also primed mice to develop a systemic serum anti-pertussis antibody response subsequent to challenge. However, pulmonary clearance of B. pertussis correlated most closely with the local antibody response. A strong anti-FHA response was demonstrated in the lungs of mice that received a booster dose of FHA 9 months after their previous exposure to FHA, demonstrating that long immunological memory can develop in the murine respiratory tract following direct application of pertussis antigens to the respiratory tract mucosa.
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PMID:Protection of mice against respiratory Bordetella pertussis infection by intranasal immunization with P.69 and FHA. 835 47

Bordetella pertussis, the causative agent of whooping cough, coordinately regulates the expression of its virulence factors in response to certain environmental stimuli. This coordinate regulation is accomplished by the bvg locus encoding the BvgS and the BvgA proteins, which are members of the two-component family of bacterial signal transducing proteins. The sensor protein BvgS shows an "unorthodox" domain structure, combining the characteristic communication modules both of the two component sensors and response regulators, each of which is indispensable for BvgS function. Although under global control of the BvgAS system, two subsets of virulence factors exemplified by the adhesin FHA and the toxins PTX and CYA exhibit, respectively, a differential mode of expression. This is reflected in a differential kinetics of transcriptional activation in vivo, and the different ability of the various virulence promoters to be expressed in the heterologous organism Escherichia coli. Evidence is accumulating that this differential regulation may be due to different affinities of the virulence promoters for the phosphorylated form of BvgA.
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PMID:Signal transduction and virulence regulation in Bordetella pertussis. 876 3

The current potency test for pertussis vaccines, the intracerebral protection test (MPT), is still the only mandatory laboratory model available. This test, however, is a valid, but inhumane and imprecise test and therefore a good candidate for replacement. Recently we have developed the Pertussis Serological Potency Test (PSPT) as an alternative for the MPT. The PSPT is based on in vitro assessment of the humoral immune response against the whole range of surface -antigens of B. pertussis in mice after immunisation with Whole Cell Vaccine (WCV). We have demonstrated a relationship between the mean pertussis antibody concentration at the day of challenge and the proportion of surviving mice at each vaccine dose in the MPT (R = 0.91). The PSPT is a model in which mice (20-24 g) are immunised i.p. with graded doses of vaccine and bled after four weeks. Sera are titrated in a whole cell ELISA and potency based on the vaccine dose-dependent antibody response is estimated by means of a parallel line analysis. In an in-house validation study 13 WCVs were tested in the PSPT and MPT. Homogeneity of both tests was proven by means of the chi-square test; potencies were significantly similar (p = 0.95). Compared to the MPT, the PSPT is more reproducible as is indicated by its smaller 95% confidence intervals. Moreover, by using the PSPT the animal distress can be reduced to an acceptable level and the PSPT also results in a reduction of more than 25% in use of mice. Additional experiments showed that estimation of WCV-potency in the PSPT based on specific antibody responses against protective antigens (PT, FHA, 69- and 92-kDa OMPS) was not possible or did not correlate with protection in MPT. Sera obtained from the PSPT showed a correlation between pertussis antibody levels and complement-mediated killing by pertussis antibodies in in vitro assays. In conclusion, the PSPT is a promising substitute for the MPT though further validation and additional studies on functional validity should finally warrant replacement of the MPT by this serological model.
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PMID:Pertussis serological potency test as an alternatively to the intracerebral mouse protection test. 878 56

The aim of this study was to compare bacteria growth and pertussis antigens (pertussis toxin-PT, filamentous haemagglutinin-FHA and endotoxin-LPS) production by 11 Bordetella pertussis strains. A synthetic Stainer-Scholte culture medium supplemented with (2,6-0-dimethyl) beta-cyclodextrin (heptakis) or methylcellulose (for greater PT and FHA production) and solid modified Cohen-Wheeler medium (for LPS isolation) were used. Our results demonstrated that heptakis and methylcellulose were more effective for antigens production than for bacterial growth. It was interesting that these stimulated substances supported the bacterial growth from small inocula. The investigated strains differed in PT, FHA and LPS production. The best PT producer was the B. pertussis 134 strain, the worst B. pertussis 2897. The differences in FHA production are not as big as in PT production, but the B. pertussis 2897 was also the worst FHA producer. Isolated LPS consists of dry bacteria pellet ranging from 1,9% (B.p. Tohama) to 5,6% (B.p. 3803 strain). No great differences in serological activity of LPS isolated from different strains were observed. In the haemagglutination inhibition test the endotoxin isolated from B.p. 509 and B.p. Tohama strains showed the highest activity.
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PMID:Bacterial growth and virulence factors production by different Bordetella pertussis strains. 927 47

Vaccine efficacy of the most efficacious acellular pertussis vaccines in the three recent placebo-controlled clinical trials, when estimated using the primary clinical case criterion, does not change substantially with the inclusion of serological confirmation in addition to culture confirmation. In the Italy trial, because of relatively high anti-PT antibody levels at the time of the acute-phase specimen in episodes of 21 or more days of paroxysmal cough, significant increases in antibody to PT are less likely to be seen in the acellular vaccine groups when evaluating children with bacterial isolation. However, the effect of this decreased sensitivity appears to be compensated by significant antibody increases in the FHA assay. When projecting a maximally sensitive criterion for serological assessment using the observed decreases in IgG antibody to PT over time following primary vaccination stratified by vaccine group, and comparing the expected antibody level with the observed level in the convalescent-phase specimen, the effect on estimated vaccine efficacy is minimal.
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PMID:Differences by antigen in seroconversion: sensitivity, specificity and bias in the serological confirmation of pertussis. 927 54

The rate of isolation of Bordetella parapertussis among children with cough during the follow-up of different clinical efficacy studies has been evaluated. In the Italian trial, a comparison of clinical characteristics between B. pertussis and B. parapertussis infections showed lower frequencies and shorter duration of typical symptoms of whooping cough such as paroxysmal coughing, whooping, and vomiting in the group of children affected with B. parapertussis infections. In about 70% of B. parapertussis infections, there was a two-fold increase of IgA or IgG anti-FHA from acute- and convalescent-phase serum specimens. The analysis of the distribution of B. parapertussis cases in children fully immunized with each pertussis vaccine suggested that vaccination is irrelevant in preventing B. parapertussis infection.
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PMID:Bordetella parapertussis infections. 927 58


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