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Multivalent mRNA-DTP vaccines are immunogenic and provide protection from Bordetella pertussis challenge in mice
M Allison Wolf1,2, Joanne M O'Hara3, Graham J Bitzer1,2
1Department of Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV, USA.
Abstract:
Acellular multivalent vaccines for pertussis (DTaP and Tdap) prevent symptomatic disease and infant mortality, but immunity to Bordetella pertussis infection wanes significantly over time resulting in cyclic epidemics of pertussis. The messenger RNA (mRNA) vaccine platform provides an opportunity to address complex bacterial infections with an adaptable approach providing Th1-biased responses. In this study, immunogenicity and challenge models were used to evaluate the mRNA platform with multivalent vaccine formulations targeting both B. pertussis antigens and diphtheria and tetanus toxoids. Immunization with mRNA formulations were immunogenetic, induced antigen specific antibodies, as well as Th1 T cell responses. Upon challenge with either historical or contemporary B. pertussis strains, 6 and 10 valent mRNA DTP vaccine provided protection equal to that of 1/20th human doses of either DTaP or whole cell pertussis vaccines. mRNA DTP immunized mice were also protected from pertussis toxin challenge as measured by prevention of lymphocytosis and leukocytosis. Collectively these pre-clinical mouse studies illustrate the potential of the mRNA platform for multivalent bacterial pathogen vaccines.
Insights
New mRNA vaccines targeting pertussis (whooping cough) and diphtheria/tetanus show promise. These adaptable vaccines provide strong immune responses and significant protection in preclinical models, potentially overcoming waning immunity from current vaccines.
Area of Science:
- Vaccinology
- Immunology
- Microbiology
Background:
- Current acellular pertussis vaccines (DTaP, Tdap) have waning immunity, leading to pertussis epidemics.
- The messenger RNA (mRNA) vaccine platform offers adaptability and potential for Th1-biased immune responses.
Purpose of the Study:
- To evaluate the immunogenicity and efficacy of an mRNA vaccine platform for multivalent bacterial pathogen vaccines.
- To assess mRNA formulations targeting Bordetella pertussis antigens, diphtheria, and tetanus toxoids.
Main Methods:
- Utilized immunogenicity and challenge models in preclinical mouse studies.
- Administered multivalent mRNA vaccine formulations targeting pertussis, diphtheria, and tetanus.
- Assessed immune responses including antigen-specific antibodies and Th1 T cell responses.
- Evaluated protection against Bordetella pertussis and pertussis toxin challenge.
Main Results:
- mRNA formulations demonstrated immunogenicity, inducing antigen-specific antibodies and Th1 T cell responses.
- 6- and 10-valent mRNA DTP vaccines provided protection comparable to low doses of DTaP or whole-cell pertussis vaccines upon challenge.
- mRNA DTP immunization protected mice from pertussis toxin challenge, preventing lymphocytosis and leukocytosis.
Conclusions:
- Preclinical studies illustrate the potential of the mRNA platform for developing multivalent bacterial vaccines.
- mRNA-based vaccines show promise for addressing complex bacterial infections like pertussis, potentially improving upon existing vaccine strategies.
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