Acellular Pertussis Vaccines Induce Anti-pertactin Bactericidal Antibodies Which Drives the Emergence of Pertactin-Negative Strains

Lesne, E.; Cavell, Breeze E.; Freire-Martin, Irene; Persaud, Ruby; Alexander, Frances; Taylor, Stephen; Matheson, Mary; van, Cécile A. C. M.; Gorringe, Andrew

doi:10.3389/fmicb.2020.02108

Cited by 35 publications

(27 citation statements)

References 97 publications

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“…These observations have recently been validated in studies by Lesne et al, who used human serum bactericidal assays to determine that antibodies to PRN, but no other aP component, are bactericidal in in vitro complement killing assays (46). These findings somewhat conflict with those of previous studies and testing methods, which often prioritize PT IgG as an indicator for protection against pertussis (4,45,47).…”

Section: Persistence Of Prn Antibodiesmentioning

confidence: 94%

Pertactin-DeficientBordetella pertussis, Vaccine-Driven Evolution, and Reemergence of Pertussis

Ma¹,

Caulfield²,

Dewan³

et al. 2021

Emerg. Infect. Dis.

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B ordetella pertussis, the causative agent of pertussis (whooping cough), continues to reemerge in countries that have high vaccine coverage, such as the United States, and has accelerated since the switch during the mid-1990s from whole-cell pertussis (wP) formulations comprising many partially characterized bacterial proteins to the less reactogenic 1-5 component acellular pertussis (aP) vaccines (1,2). These aP vaccines, including DTaP (diphtheria, tetanus, and aP for children) and Tdap (tetanus, diphtheria, and aP for adolescents and adults), protect against disease, but this protection wanes rapidly and does not prevent colonization or transmission of the pathogen (3-5). In this background of suboptimally performing aP vaccines, many countries have noted the emergence and expansion of strains specifi cally lacking pertactin (PRN), a membrane bound autotransporter, and 1 of up to 5 B. pertussis protein antigens included in the vaccines (6-11).

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Section: Persistence Of Prn Antibodiesmentioning

confidence: 94%

Pertactin-DeficientBordetella pertussis, Vaccine-Driven Evolution, and Reemergence of Pertussis

Ma¹,

Caulfield²,

Dewan³

et al. 2021

Emerg. Infect. Dis.

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“…Of particular interest, engineering vaccines that promote antibodies with opsonophagocytic and/or bactericidal activity may improve efficacy (30). There are discrepancies between the existing studies investigating opsonophagocytic and bactericidal activities induced by aP vaccines (31,32). In a study by Lesne and colleagues, contribution of PRN to generate complement-mediated bactericidal antibodies has been reported while anti-FIM, anti-FHA, and anti-PT antibodies against pertussis were not involved (31).…”

Section: Discussionmentioning

confidence: 99%

“…There are discrepancies between the existing studies investigating opsonophagocytic and bactericidal activities induced by aP vaccines (31,32). In a study by Lesne and colleagues, contribution of PRN to generate complement-mediated bactericidal antibodies has been reported while anti-FIM, anti-FHA, and anti-PT antibodies against pertussis were not involved (31). However, some controversies remain as other studies showed that levels of anti-PT and FIM antibodies directly correlated with the protection in humans (32,33).…”

Section: Discussionmentioning

confidence: 99%

Anti-FIM and Anti-FHA Antibodies Inhibit Bordetella pertussis Growth and Reduce Epithelial Cell Inflammation Through Bacterial Aggregation

Yougbaré

McTague

et al. 2020

Front. Immunol.

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The pertussis vaccination is highly recommended for infants, children, and pregnant women. Despite a high coverage of vaccination, pertussis continues to be of public health concern as a re-emerging infectious disease. The mechanism by which vaccine-elicited anti-pertussis antibodies mediate direct bactericidal effects is poorly understood. In this study, we showed that the interaction of B. pertussis with A549 epithelial cells induce release of biological factors which enhance bacteria growth. Complement-depleted antisera from vaccine-immunized guinea pigs or monoclonal antibodies targeting FHA and FIM mediate bacteria aggregation and elicit bactericidal effects. Our in vitro results indicated that aggregation of bacteria through anti-FIM and anti-FHA specific antibodies is one of the major biological mechanisms to clear bacterial infections and restore epithelial cell survival in vitro. Our data also indicates that the anti-pertussis antibodies reduce secretion of proinflammatory chemokines and cytokines by preventing interaction of B. pertussis with host cells. The results of this study not only demonstrate mechanism of action of anti-FIM and anti-FHA antibodies, but also opens translational applications for potential therapeutic approaches or development of analytical assays such as in vitro potency assays.

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“…For the sub-study investigating functional aspects of antipertussis vaccine antigen immunity a smaller set of samples will be used. Details will be provided to the laboratory team and the aliquots from the cord and infant samples of these participants will be transferred to the pathogen immunology group to be analysed using a serum bactericidal antibody assay 19 .…”

Section: Serummentioning

confidence: 99%

“…The collection of safety data in studies involving vaccination in pregnancy raises specific issues and it is important that the information collected about some outcomes of special interest is collected as consistently as possible 19 .…”

Section: Specific Issues For Studies In Pregnancymentioning

confidence: 99%

Optimising the Timing of whooping cough Immunisation in MUMs: a randomised controlled trial investigating the timing of pertussis vaccination in pregnancy (OpTIMUM): a protocol paper

et al. 2021

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Background: Pertussis is a highly infectious respiratory illness caused by the bacteria Bordetella pertussis. A resurgence of pertussis, even in countries with good vaccine coverage, has led to an increase in infant deaths. In response to this, many countries have introduced pertussis vaccination in pregnancy. This strategy is effective at preventing infant disease, but there remains uncertainty about what gestational timing is best to ensure maximal protection of the infant. These uncertainties are the rationale for this randomised controlled trial and a sub-study investigating pertussis-specific antibody in breastmilk. Protocol: We will recruit 354 pregnant women and will randomise them to receive their pertussis vaccination in one of three gestational age windows: ≤23+6, 24-27+6 and 28-31+6 weeks of gestation. Vaccination will be with Boostrix-IPV® and participants will be asked to complete a symptom diary for seven days following vaccination. Blood sampling will be performed prior to vaccination, two weeks following vaccination and at the time of delivery. A cord blood sample will be collected at delivery and a blood sample collected from the infant 4-10 weeks after completion of the primary immunisations. Individuals participating in the breastmilk sub-study will provide a sample of colostrum within 48 hours of delivery and samples of breastmilk at two weeks and around five-six months. Blood samples will be analysed using enzyme linked immunosorbent assay (ELISA) techniques for pertussis toxin, filamentous haemagglutinin and pertactin. A subset of serum samples will also be analysed using a functional assay. Colostrum and breastmilk samples will be analysed using functional assays. Discussion: Although pertussis vaccination has been shown to be safe and effective in pregnancy there remains debate about the optimal timing for the administration during pregnancy. This study will investigate antibody responses in serum and breastmilk when vaccination is performed in three different time periods. Clinicaltrials.gov registration: NCT03908164 (09/04/2019)

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Acellular Pertussis Vaccines Induce Anti-pertactin Bactericidal Antibodies Which Drives the Emergence of Pertactin-Negative Strains

Cited by 35 publications

References 97 publications

Pertactin-DeficientBordetella pertussis, Vaccine-Driven Evolution, and Reemergence of Pertussis

Pertactin-DeficientBordetella pertussis, Vaccine-Driven Evolution, and Reemergence of Pertussis

Anti-FIM and Anti-FHA Antibodies Inhibit Bordetella pertussis Growth and Reduce Epithelial Cell Inflammation Through Bacterial Aggregation

Optimising the Timing of whooping cough Immunisation in MUMs: a randomised controlled trial investigating the timing of pertussis vaccination in pregnancy (OpTIMUM): a protocol paper

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