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Research roadmap for coronavirus vaccine development

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Rationally attenuated candidates

Dependencies

Next steps

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  • Outdated technology: Current vaccines are successful but rely on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