Coronaviruses roadmap:
Vaccines
Research roadmap for coronavirus vaccine development
Download 202402 Draft Coronavirus Vaccine research roadmap Final3
Rationally attenuated candidates
Rationally attenuated candidates
Research Question
- The goal is to develop stable, rationally attenuated vaccines for animal
coronaviruses that are safe, effective, and most importantly do not
revert to virulent forms, which is a problem with older-LAVs. These
vaccines should induce strong immune responses while minimizing the
risks of viral shedding and recombination, both of which are particular
challenges with LAVs
Research Gaps and Challenges
- Risk of shedding, reversion and reassortment: LAVs, while effective,
carry the risk of reversion and/or shedding, whereby animals can also
spread the virus. Connected to this is reassortment, where
recombination occurs with circulating strains. This could lead to the
emergence of virulent or immune escape variants, complicating control
efforts - Attenuation genetic stability: Identifying, characterizing and validating
the genetic changes that stably attenuate candidate virus vaccines
without the risk of reversion is critical. There is also a need to
understand how conserved they are across different coronavirus
strains, species and also susceptible hosts - Outdated technology: Current vaccines are successful but rely on
passage of virus, which is an outdate technology and continually needs
to be adapted when new virus strains emerge. Efforts needs to be
made to advance technology for example, using live attenuated
vectored vaccines. Considerations will need to be given to issues such
as affordability
Solution Routes
- As above for LAVs we can use genetic engineering techniques, such as
reverse genetics, to introduce stable attenuating mutations in key viral
genes. These mutations need to strike the right balance between
attenuating the virus but preserving its immunogenicity - Integrate attenuation with DIVA capabilities: Develop DIVA vaccines
that allow for the simultaneous use of diagnostic tests. These rationally
attenuated vaccines could also add markers that allow DIVA, aiding in
surveillance and disease control - Improving understanding and modelling of immune escape: Develop
better data sets and build predictive models to monitor (and predict)
viral evolution and recombination events in the field that might bypass
vaccine-induced immunity
Dependencies
- Diagnostic tools for DIVA vaccines: Reliable and sensitive diagnostic
tools must be developed to accompany DIVA vaccines.
Surveillance systems: Surveillance systems are needed to monitor for
vaccine strain reversion and recombination with circulating strains,
particularly in regions with high viral diversity. This is essential for
ensuring the long-term safety and efficacy of attenuated vaccines
State Of the Art
- Rational attenuation of live virus for vaccines for coronaviruses could
provide strong immunity, more than inactivated vaccines, for example.
However, they carry the risk of reversion. From an animal coronavirus
perspective they are cost-effective for mass vaccinations in livestock
and pets
Projects
What activities are planned or underway?
Differential susceptibility of SARS-CoV-2 in animals : Evidence of ACE2 host receptor distribution in companion animals, livestock and wildlife by immunohistochemical characterisation
Planned Completion date 26/07/2021
Participating Country(s):
Netherlands
Veterinary Biocontained facility Network for excellence in animal infectiology research and experimentation
Planned Completion date 28/02/2023
Participating Country(s):
Europe