Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons

Nguyen, Annalee W.; DiVenere, Andrea M.; Papin, James F.; Connelly, Sheila; Kaleko, Michael; Maynard, Jennifer A.

doi:10.1126/sciadv.aay9258

Cited by 33 publications

(25 citation statements)

References 45 publications

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“…2 and 7 ). Nguyen et al also demonstrated that the anti-PT antibody hu1B7 can prevent leukocytosis and other clinical features of pertussis infection in a neonatal baboon model, further supporting its benefit in protection ( 51 ). Additionally, individuals who have higher anti-PT antibodies after immunization are better protected from infection and have decreased disease severity in households with B. pertussis exposure ( 52 ).…”

Section: Discussionmentioning

confidence: 95%

Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice

et al. 2021

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Bordetella pertussis colonizes the respiratory mucosa of humans, inducing an immune response seeded in the respiratory tract. An individual, once convalescent, exhibits long-term immunity to the pathogen. Current acellular pertussis (aP) vaccines do not induce the long-term immune response observed after natural infection in humans. In this study, we evaluated the durability of protection from intranasal (IN) pertussis vaccines in mice. Mice that convalesced from B. pertussis infection served as a control group. Mice were immunized with a mock vaccine (PBS), aP only, or an aP base vaccine combined with one of the following adjuvants: alum, curdlan, or purified whole glucan particle (IRI-1501). We utilized two study designs: short-term (challenged 35 days post-priming vaccination) and long-term (challenged six months post-boost). The short-term study demonstrated that immunization with IN vaccine candidates decreased bacterial burden in the respiratory tract, reduced markers of inflammation, and induced significant serum and lung antibody titers. In the long-term study, protection from bacterial challenge mirrored the results observed in the short-term challenge study. Immunization with pertussis antigens alone was surprisingly protective in both models; however, the alum and IRI-1501 adjuvants induced significant B. pertussis specific IgG antibodies in both the serum and lung, and increased numbers of anti-B. pertussis IgG secreting plasma cells in the bone marrow. Our data indicate that humoral responses induced by the IN vaccines correlated with protection, suggesting that long-term antibody responses can be protective.

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Section: Discussionmentioning

confidence: 95%

Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice

et al. 2021

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“…Upon injection they induce specific systemic antibodies important to prevent pertussis disease ( 75 , 76 ), but fail to induce mucosal antibodies that may be important to prevent colonization by and transmission of the pathogen ( 64 ). Few studies have evaluated antibody responses after mucosal administration of DTwP in human volunteers.…”

Section: Resultsmentioning

confidence: 99%

Mucosal Immunization Against Pertussis: Lessons From the Past and Perspectives

Dubois

Locht

2021

Front. Immunol.

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BackgroundCurrent vaccination strategies against pertussis are sub-optimal. Optimal protection against Bordetella pertussis, the causative agent of pertussis, likely requires mucosal immunity. Current pertussis vaccines consist of inactivated whole B. pertussis cells or purified antigens thereof, combined with diphtheria and tetanus toxoids. Although they are highly protective against severe pertussis disease, they fail to elicit mucosal immunity. Compared to natural infection, immune responses following immunization are short-lived and fail to prevent bacterial colonization of the upper respiratory tract. To overcome these shortcomings, efforts have been made for decades, and continue to be made, toward the development of mucosal vaccines against pertussis.ObjectivesIn this review we systematically analyzed published literature on protection conferred by mucosal immunization against pertussis. Immune responses mounted by these vaccines are summarized.MethodThe PubMed Library database was searched for published studies on mucosal pertussis vaccines. Eligibility criteria included mucosal administration and the evaluation of at least one outcome related to efficacy, immunogenicity and safety.ResultsWhile over 349 publications were identified by the search, only 63 studies met the eligibility criteria. All eligible studies are included here. Initial attempts of mucosal whole-cell vaccine administration in humans provided promising results, but were not followed up. More recently, diverse vaccination strategies have been tested, including non-replicating and replicating vaccine candidates given by three different mucosal routes: orally, nasally or rectally. Several adjuvants and particulate formulations were tested to enhance the efficacy of non-replicating vaccines administered mucosally. Most novel vaccine candidates were only tested in animal models, mainly mice. Only one novel mucosal vaccine candidate was tested in baboons and in human trials.ConclusionThree vaccination strategies drew our attention, as they provided protective and durable immunity in the respiratory tract, including the upper respiratory tract: acellular vaccines adjuvanted with lipopeptide LP1569 and c-di-GMP, outer membrane vesicles and the live attenuated BPZE1 vaccine. Among all experimental vaccines, BPZE1 is the only one that has advanced into clinical development.

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“…Despite high B. pertussis colonization following B. pertussis challenge, infant baboons born to mothers vaccinated with the PTX mono-component vaccine show no disease symptoms, compared to baboons born to unvaccinated mothers that have the disease ( Kapil et al, 2018 ). Another study reports that anti-PTX antibody hu1B7 is sufficient to prevent and treat clinical pertussis symptoms ( Nguyen et al, 2020 ). These results suggest that PTX, which is mainly secreted, induces toxin-neutralizing antibodies which are sufficient to protect against pertussis disease.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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Despite high vaccination coverage, Bordetella pertussis the causative agent of whooping cough is still a health concern worldwide. A resurgence of pertussis cases has been reported, particularly in countries using acellular vaccines with waning immunity and pathogen adaptation thought to be responsible. A better understanding of protective immune responses is needed for the development of improved vaccines. In our study, B. pertussis strain B1917 variants presenting a single gene deletion were generated to analyze the role of vaccine components or candidate vaccine antigens as targets for bactericidal antibodies generated after acellular vaccination or natural infection. Our results show that acellular vaccination generates bactericidal antibodies that are only directed against pertactin. Serum bactericidal assay performed with convalescent samples show that disease induces bactericidal antibodies against Prn but against other antigen(s) as well. Four candidate vaccine antigens (CyaA, Vag8, BrkA, and TcfA) have been studied but were not targets for complement-mediated bactericidal antibodies after natural infection. We confirm that Vag8 and BrkA are involved in complement resistance and would be targeted by blocking antibodies. Our study suggests that the emergence and the widespread circulation of Prn-deficient strains is driven by acellular vaccination and the generation of bactericidal antibodies targeting Prn.

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Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons

Cited by 33 publications

References 45 publications

Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice

Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice

Mucosal Immunization Against Pertussis: Lessons From the Past and Perspectives

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

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