Overcoming Waning Immunity in Pertussis Vaccines: Workshop of the National Institute of Allergy and Infectious Diseases

Damron, F. Heath; Barbier, Mariette; Dubey, Purnima; Edwards, Kathryn M.; Gu, Xin-Xing; Klein, Nicola P.; Lu, Kristina T.; Mills, Kingston H. G.; Pasetti, Marcela F.; Read, Robert C.; Rohani, Pejman; Šebo, Peter; Harvill, Eric T.

doi:10.4049/jimmunol.2000676

Cited by 23 publications

(17 citation statements)

References 37 publications

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“…Pertussis, a highly contagious respiratory disease mainly caused by the Gram-negative bacterium Bordetella pertussis, has resurged in many countries even in those with high vaccination coverage (1)(2)(3)(4)(5). In order to confront this worrying epidemiological situation in the short term, vaccination schedules have been modified in many countries by implementing additional boosters (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…This situation requires a third generation of vaccines with the capacity to overcome such weaknesses in the medium-long term ( 11 ). Thus, this new generation of vaccines must be i) safer than wP, ii) able to induce an immune response profile that is mostly Th1 and Th17 ( 12 ) with proliferation of the memory cell population resident in tissues ( 13 , 14 ), iii) made up of multiple epitopes to minimize the selection pressure that it may exert on the circulating bacterial population, iv) able to protect against the circulating bacterial population, and v) biotechnologically easy to produce, ensuring accessibility to the entire population ( 5 , 15 ).…”

Section: Introductionmentioning

confidence: 99%

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Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture

et al. 2021

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Outer membrane vesicles (OMV) derived from Bordetella pertussis—the etiologic agent of the resurgent disease called pertussis—are safe and effective in preventing bacterial colonization in the lungs of immunized mice. Vaccine formulations containing those OMV are capable of inducing a mixed Th1/Th2/Th17 profile, but even more interestingly, they may induce a tissue-resident memory immune response. This immune response is recommended for the new generation of pertussis-vaccines that must be developed to overcome the weaknesses of current commercial acellular vaccines (second-generation of pertussis vaccine). The third-generation of pertussis vaccine should also deal with infections caused by bacteria that currently circulate in the population and are phenotypically and genotypically different [in particular those deficient in the expression of pertactin antigen, PRN(-)] from those that circulated in the past. Here we evaluated the protective capacity of OMV derived from bacteria grown in biofilm, since it was observed that, by difference with older culture collection vaccine strains, circulating clinical B. pertussis isolates possess higher capacity for this lifestyle. Therefore, we performed studies with a clinical isolate with good biofilm-forming capacity. Biofilm lifestyle was confirmed by both scanning electron microscopy and proteomics. While scanning electron microscopy revealed typical biofilm structures in these cultures, BipA, fimbria, and other adhesins described as typical of the biofilm lifestyle were overexpressed in the biofilm culture in comparison with planktonic culture. OMV derived from biofilm (OMVbiof) or planktonic lifestyle (OMVplank) were used to formulate vaccines to compare their immunogenicity and protective capacities against infection with PRN(+) or PRN(-) B. pertussis clinical isolates. Using the mouse protection model, we detected that OMVbiof-vaccine was more immunogenic than OMVplank-vaccine in terms of both specific antibody titers and quality, since OMVbiof-vaccine induced antibodies with higher avidity. Moreover, when OMV were administered at suboptimal quantity for protection, OMVbiof-vaccine exhibited a significantly adequate and higher protective capacity against PRN(+) or PRN(-) than OMVplank-vaccine. Our findings indicate that the vaccine based on B. pertussis biofilm-derived OMV induces high protection also against pertactin-deficient strains, with a robust immune response.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture

et al. 2021

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“…Pre-clinical animal models of vaccination and challenge have provided important insights into pertussis immunity. However, the majority of the recent conversations around pertussis vaccine immunity are focused on the pertussis T helper and T memory cell responses 57,86,87 . Furthermore, "longevity of protection" markers have not truly been identified in neither animals nor humans.…”

Section: Discussionmentioning

confidence: 99%

“…However, the value of some of these antibodies in protection against pertussis disease or B. pertussis infection is highly debated 57 . Here, we hypothesized that antibody responses to B. pertussis antigens in aP immunized mice would decrease over time compared to wP immunized mice.…”

Section: Pertussis Specific Antibody Responses To Ap and Wp Immunization Persist As Far As Day 532 Post-primementioning

confidence: 99%

Long-term analysis of pertussis vaccine immunity uncovers a memory B cell response to whole cell pertussis immunization that is absent from acellular immunized mice

Weaver

Blackwood

Horspool

et al. 2021

Preprint

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Over two decades ago acellular pertussis vaccines (aP) replaced whole cell pertussis vaccines (wP) in several countries. Since then, a resurgence in pertussis has been observed, which is hypothesized to be linked to waning immunity. To better understand why waning immunity occurs, we developed a long-term outbred CD1 mouse model to conduct the longest murine pertussis vaccine studies to date, spanning out to 532 days post primary immunization. Vaccine-induced memory results from follicular responses and germinal center formation; therefore, cell populations and cytokines involved with memory were measured alongside protection from challenge. Both aP and wP immunization elicit protection from intranasal challenge and generation of pertussis specific antibody responses in mice. Responses to wP vaccination were characterized by a significant increase in T follicular helper cells in the draining lymph nodes and CXCL13 levels in sera compared to aP mice. In addition, a population of B. pertussis + memory B cells was found to be unique to wP vaccinated mice. This population peaked post-boost, and was measurable out to day 365 post-vaccination. Anti- B. pertussis and anti-pertussis toxoid antibody secreting cells increased one day after boost and remained high at day 532. The data suggest that follicular responses, and in particular CXCL13 levels in sera, should be monitored in pre-clinical and clinical studies for the development of the next-generation pertussis vaccines.

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“…There is no consensus regarding the reasons for increases in overall incidence of pertussis over time [43][44][45]. Multiple factors might play a role, including waning vaccine effectiveness, inability of vaccines to prevent colonization and mutation in circulating pertussis strains.…”

Section: Factors Contributing To Increased Incidence and Shift In Disease Burdenmentioning

confidence: 99%

Lessons from a mature acellular pertussis vaccination program and strategies to overcome suboptimal vaccine effectiveness

Zerbo

Fireman

Klein

2021

Expert Review of Vaccines

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Introduction: Despite high vaccination coverage among children and adolescents, pertussis remains a public health problem, with large outbreaks occurring periodically in the US and other developed countries. Areas covered: We examine lessons learned more than 20 years after implementation of programs which use only acellular pertussis vaccines and propose avenues for possible effective use of acellular pertussis vaccine to prevent large outbreaks. Expert Opinion: Acellular pertussis vaccines were introduced more than 20 years ago, yet the incidence of pertussis has been increasing over the past decade, with periodic large outbreaks marked by notable shifts in disease burden from infants and young children toward fully vaccinated adolescents and young adults. This age shift is mainly driven by the waning of vaccine immunity. To better protect adolescents against pertussis, modification of the current acellular pertussis vaccination schedule or adoption of new vaccination strategies should be considered. For infants not yet eligible to be vaccinated, maternal vaccination against pertussis during pregnancy is an effective way to protect infants from infection, severe disease and death. Implementation of maternal vaccination programs should be encouraged in countries without one or efforts to improve coverage should be supported in countries with existing program.

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Overcoming Waning Immunity in Pertussis Vaccines: Workshop of the National Institute of Allergy and Infectious Diseases

Cited by 23 publications

References 37 publications

Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture

Pertussis Vaccine Candidate Based on Outer Membrane Vesicles Derived From Biofilm Culture

Long-term analysis of pertussis vaccine immunity uncovers a memory B cell response to whole cell pertussis immunization that is absent from acellular immunized mice

Lessons from a mature acellular pertussis vaccination program and strategies to overcome suboptimal vaccine effectiveness

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