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Immunization with an mRNA DTP vaccine protects against pertussis in rats.

ABSTRACT: Bordetella pertussis is a Gram-negative bacterium that is the causative agent of the respiratory disease known as pertussis. Since the switch to the acellular vaccines of DTaP and Tap, pertussis cases in the US have risen and cyclically fallen. We have observed that mRNA pertussis vaccines are immunogenic and protective in mice. Here, we further evaluated the pertussis toxoid mRNA antigen and refined the formulation based on optimal pertussis toxin neutralization in vivo. We next evaluated the mRNA pertussis vaccine in Sprague-Dawley rats using an aerosol B. pertussis challenge model paired with whole-body plethysmography to monitor coughing and respiratory function. Female Sprague-Dawley rats were primed and boosted with either commercially available vaccines (DTaP or wP-DTP), an mRNA-DTP vaccine, or mock-vaccinated. The mRNA-DTP vaccine was immunogenic in rats and induced antigen-specific IgG antibodies comparable to DTaP. Rats were then aerosol challenged with a streptomycin-resistant emerging clinical isolate D420Sm1. Bacterial burden was assessed at days 1 and 9 post-challenge, and the mRNA vaccine reduced burden equal to both DTaP and wP-DTP. Whole-body plethysmography revealed that mRNA-DTP vaccinated rats were well protected against coughing which was comparable to the non-challenged group. These data suggest that an mRNA-DTP vaccine is immunogenic in rats and provides protection against aerosolized B. pertussis challenge in Sprague-Dawley rats.

SUBMITTER: Bitzer GJ

PROVIDER: S-EPMC11320933 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Immunization with an mRNA DTP vaccine protects against pertussis in rats.

Bitzer Graham J GJ Fitzgerald Nicholas A NA DeJong Megan A MA Cunningham Casey C Chapman Joshua A JA Boehm Dylan T DT Pyles Gage M GM Huckaby Annalisa B AB Miller Sarah J SJ Dublin Spencer R SR Warden Matthew D MD Barbier Mariette M Damron F Heath FH

Infection and immunity 20240717 8

<i>Bordetella pertussis</i> is a Gram-negative bacterium that is the causative agent of the respiratory disease known as pertussis. Since the switch to the acellular vaccines of DTaP and Tap, pertussis cases in the US have risen and cyclically fallen. We have observed that mRNA pertussis vaccines are immunogenic and protective in mice. Here, we further evaluated the pertussis toxoid mRNA antigen and refined the formulation based on optimal pertussis toxin neutralization <i>in vivo</i>. We next e ...[more]

PMID: 39016553

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Project description:Whole-cell pertussis (wP) vaccines introduced in the 1940s led to a dramatic reduction of pertussis incidence and are still widely used in low- and middle-income countries (LMICs) worldwide. The reactogenicity of wP vaccines resulted in reduced public acceptance, which drove the development and introduction of acellular pertussis (aP) vaccines in high-income countries in the 1990s. Increased incidence of pertussis disease has been observed in high-income countries following the introduction of aP vaccines despite near universal rates of pediatric vaccination. These increases are attributed to the reduced protection against colonization, carriage, and transmission as well as reduced duration of immunity conferred by aP vaccines relative to the wP vaccines they replaced. A reduced reactogenicity whole-cell pertussis (RRwP) vaccine was recently developed with the goal of achieving the same protection as conferred by wP vaccination but with an improved safety profile, which may benefit countries in which wP vaccines are still in routine use. In this study, we tested the RRwP vaccine in a baboon model of pertussis infection. We found that the RRwP vaccine induced comparable cellular and humoral immune responses and comparable protection following challenge relative to the wP vaccine, while significantly reducing injection-site reactogenicity.IMPORTANCEThe World Health Organization (WHO) recommended in 2015 that countries administering wP vaccines in their national vaccine programs should continue to do so, and that switching to aP vaccines for primary infant immunization should only be considered if periodic booster vaccinations and/or maternal immunization could be assured and sustained in their national immunization schedules (WHO, Vaccine 34:1423-1425, 2016, https://doi.org/10.1016/j.vaccine.2015.10.136). Due to the considerably higher cost of aP vaccines and the larger number of doses required, most LMICs continue to use wP vaccines. The development and introduction of a wP vaccine that induces fewer adverse events without sacrificing protection would significantly benefit countries in which wP vaccines are still in routine use. The results of this study indicate this desirable goal may be achievable.

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Immunization with an mRNA DTP vaccine protects against pertussis in rats.

Publications

Immunization with an mRNA DTP vaccine protects against pertussis in rats.

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