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Immunization with an mRNA DTP vaccine protects against pertussis in rats
Graham J Bitzer1,2, Nicholas A Fitzgerald1,2, Megan A DeJong1,2
1Department of Microbiology, Immunology, and Cell Biology, West Virginia University , Morgantown, West Virginia, USA.
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.
Insights
New mRNA pertussis vaccines show promise, demonstrating immunogenicity and protection against Bordetella pertussis challenge in rats. These findings suggest a potential new strategy for pertussis prevention.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Pertussis, caused by Bordetella pertussis, remains a concern despite current acellular vaccines (DTaP, Tdap), with rising and falling case numbers.
- Previous studies indicated mRNA pertussis vaccines are immunogenic and protective in mice.
Purpose of the Study:
- To evaluate an mRNA pertussis vaccine's efficacy in a rat model.
- To refine mRNA vaccine formulation for optimal pertussis toxin neutralization.
- To assess protection against Bordetella pertussis challenge and its impact on respiratory function.
Main Methods:
- Female Sprague-Dawley rats were vaccinated with mRNA-DTP, DTaP, wP-DTP, or mock vaccine.
- Rats were challenged via aerosol with Bordetella pertussis (D420Sm1).
- Bacterial burden, IgG antibody levels, and respiratory function (coughing) were assessed using plethysmography.
Main Results:
- The mRNA-DTP vaccine was immunogenic, inducing comparable antigen-specific IgG antibodies to DTaP.
- mRNA-DTP vaccination significantly reduced bacterial burden, similar to DTaP and wP-DTP.
- mRNA-DTP vaccinated rats showed protection against coughing, comparable to unvaccinated controls.
Conclusions:
- The mRNA-DTP vaccine is immunogenic in rats.
- This mRNA vaccine provides protection against aerosolized Bordetella pertussis challenge.
- The findings support the potential of mRNA technology for developing new pertussis vaccines.
