Research roadmap for coronavirus vaccine development

Download 202402 Draft Coronavirus Vaccine research roadmap Final

Vectored vaccines

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Dependencies

11 Vector

Next steps

1 Vaccine

Vectored vaccines

Research Question

To develop safe and effective vectored vaccines for coronaviruses in pets, livestock, and wildlife

Research Gaps and Challenges

Vector safety and stability: Ensuring that vaccine vectors are safe, nonpathogenic, and stable in diverse animal species
Pre-existing immunity to viral vectors: Pre-existing immunity to viral
vectors (like adenoviruses or measles viruses) in animals can reduce
the efficacy of vectored vaccines
Efficient vaccine delivery to wildlife: Delivering vaccines to large
populations of livestock or free-ranging wildlife is logistically
challenging
Cross-species transmission: The risk of vaccine vectors spreading from
vaccinated animals to non-target species, including humans, poses a
safety risk
Cost and scalability: The cost of producing vectored vaccines and
scaling them for large populations, especially in wildlife or low resource livestock farming environments, can be prohibitive
Understanding host-specific immunity: The immune systems of pets,
livestock, and wild animals, vary significantly. A vaccine vector that
works well in one species might not elicit the same immune response
in another
Ecological and evolutionary impacts in wildlife: The mass vaccination
of wildlife with vectored vaccines may have unforeseen ecological
consequences, such as altering predator-prey dynamics or influencing
viral evolution in non-target species

Solution Routes

Determine the most suitable vectors
Develop next-generation vector platforms, such as novel or less
common viral vectors that avoid pre-existing immunity
New approaches are needed for vaccine/ immunogen design to
achieve robust protection
Engineer vectors to be more thermostable, enabling easier storage and
transport for use in remote or resource-poor environments
Educational campaigns about new vaccine strategies and platforms

Dependencies

Funding: Increased funding is needed for comparative immunology
studies across species, particularly wild animals
Immune system response to infection: Detailed research into how
different species’ immune systems respond to coronavirus infection
and vaccination is required. This includes understanding differences in
innate, mucosal, and adaptive immune responses
Route of delivery: Evaluate alternate routes of vaccine delivery
(intranasal, oral, topical)
Assay techniques and endpoints: Interlaboratory variability in assay techniques and assay endpoints limits comparison among measurements of immunogenicity. Standardized and harmonised assays and protocols are required
Animal models: Establishment of reliable animal models for studying coronavirus infections in pets, livestock, and wildlife for preclinical vaccine testing

State Of the Art

Several well-known vectors offer the possibility of protection against
coronavirus infection (e.g. poxvirus, adenovirus, measles, and
togavirus). If these vectors are reasonably safe, they are limited to
presenting one or a reduced number of coronavirus antigens to the
immune system (Enjuanes, L., et al. “Molecular basis of coronavirus
virulence and vaccine development.” Advances in virus research 96
(2016): 245-286.)
ChAdOx1 and MVA based vaccines have been used against MERS in
camels https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413082/
https://www.nature.com/articles/d42473-018-00392-7
https://www.thelancet.com/journals/langlo/article/PIIS2214-
109X%2823%2900164-X/fulltext
Other vectors of interest are vesicular stomatitis virus (VSV)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359519/;
https://www.sciencedirect.com/science/article/pii/S1931312820303619; https://www.vet.cornell.edu/research/awards/202105/two-vaccineplatforms-prevent-feline-coronavirus-disease used for feline infectious peritonitis (FIP)
Newcastle Disease Virus (NDV): NDV vectors have been used in poultry vaccines with success and are now being studied for potential use against avian coronaviruses.
https://www.sciencedirect.com/science/article/pii/S2352396420305089; https://www.nature.com/articles/s41467-021-26499-y
Venezuelan equine encephalitis virus (VEE):
https://pubmed.ncbi.nlm.nih.gov/20980507/
Rabies virus vectors are well-established in veterinary medicine,
particularly for wild animal vaccination programmes.
https://jdc.jefferson.edu/mifp/119/;
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229041/
Parainfluenza virus (PIV): https://pubmed.ncbi.nlm.nih.gov/15220033/