Development of mRNA-Based Vaccine Platforms Against Emerging Zoonotic Pathogens
DOI:
https://doi.org/10.5281/zenodo.22688130Keywords:
mRNA vaccines, lipid nanoparticles, zoonotic pathogens, self-amplifying RNA, pandemic preparedness, Nipah virusAbstract
The rapid clinical translation of mRNA vaccines against SARS-CoV-2 demonstrated that a
lipid-nanoparticle-formulated messenger RNA platform can move from sequence to authorised vaccine in under a
year, a timeline that has since reshaped expectations for how the field should respond to future zoonotic spillover
events. This review synthesises the current state of mRNA vaccine development against six zoonotic pathogens
judged by the World Health Organization and comparable bodies to carry substantial pandemic potential -- Nipah
virus, Lassa virus, Middle East respiratory syndrome coronavirus, highly pathogenic avian influenza H5N1, Rift
Valley fever virus, and mpox virus -- drawing on 61 peer-reviewed sources spanning preclinical immunogenicity
studies, completed and ongoing clinical trials, and platform technology development. Across candidates in at least
Phase 1 clinical evaluation, mRNA platforms have generally shown favourable reactogenicity and immunogenicity
profiles comparable to or exceeding recombinant protein and viral-vector comparators, with self-amplifying RNA
constructs achieving equivalent neutralising antibody titres at substantially lower RNA doses than conventional
non-replicating mRNA in head-to-head preclinical comparisons. Persistent technical obstacles include lipid
nanoparticle cold-chain requirements that limit deployability in the resource-limited settings where several target
pathogens are endemic, incompletely characterised long-term durability of mRNA-induced immunity relative to
some live-attenuated comparators, and, for several target pathogens, an absence of correlates of protection that
complicates efficacy-trial design in the typically small and geographically restricted outbreak settings where these
pathogens circulate. We conclude that mRNA platforms are a credible and in several respects favourable
technology for pandemic-potential zoonotic pathogen vaccine development, but that platform-level advantages
demonstrated during the COVID-19 pandemic response will not translate automatically to pathogens lacking
equivalent manufacturing scale, regulatory precedent, and sustained funding commitment.
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