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Coronaviruses roadmap:
Vaccines

Research roadmap for coronavirus vaccine development

Download 202402 Draft Coronavirus Vaccine research roadmap Final

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Subunit vaccines

Next steps

Subunit vaccines

Research Question

  • What are we trying to achieve?
    To develop safe and effective subunit vaccines for animal
    coronaviruses to safeguard animal health
  • What is the problem we are trying to solve?
    Other vaccine strategies employ live or attenuated vaccines, which may
    result in reversion, infection or transmission in vaccinated animals, so
    subunit vaccines provide a safe and relatively stable alternative, where
    the technology is already well-established

Research Gaps and Challenges

  • Weaker immune response: Antigens used to elicit immunes responses
    may lack molecular structures (e.g., PAMPs), so do not infect cells.
    Therefore, these antigens mainly only trigger antibody-mediated
    immune responses, with weaker cell-mediated T cell responses.
  • Longevity of immune response: Adjuvants and boosters may be
    required to enhance the immune response, or boost a waning
    response over time, which may not be ideal for use in animals. This
    would also require the development of suitable adjuvants for animals
    in which subunit vaccines are not routinely used
  • Purity: Subunit vaccines are made in bacteria/yeast/insect/mammalian expression systems, so require substrates to grow them and can become expensive, particularly if purifying and concentrating vaccine preparations. This method also requires care to avoid contamination with other organisms
  • Speed: Determining the correct antigen, or part of antigen to use as
    the immunogen can take time to design and synthesise, so may be a
    slow process if a vaccine is required urgently
  • Strain diversity: Animal coronaviruses exhibit significant genetic
    diversity, so it is difficult to design a universal subunit vaccine based on the spike protein of one coronavirus. Different subunit vaccines may need to be produced that are virus strain or animal species specific, which limits their universality and will be more expensive long-term to manufacture

Solution Routes

  • Expression system: Mammalian expression system are generally
    cleaner and produce fewer contaminants than other expression
    systems, so may be used as a preference. These expression systems
    also allow the production of large amounts of protein, which is ideal for generating high yields of vaccine quickly
  • More specific immunogens: Target conserved components of the
    coronavirus genome to develop vaccines (e.g., RBD, S1), that may elicit
    broader immune responses across several coronaviruses
  • Multivalent vaccines: As subunit vaccines only contain a small amount
    of virus genetic material, which is usually synthetic, a multivalent
    approach could be taken to incorporate the spike of more divergent
    coronaviruses and help to elicit a broader immune response

Dependencies

  • Expression system: Mammalian expression system are generally
    cleaner and produce fewer contaminants than other expression
    systems, so may be used as a preference. These expression systems
    also allow the production of large amounts of protein, which is ideal for generating high yields of vaccine quickly
  • More specific immunogens: Target conserved components of the
    coronavirus genome to develop vaccines (e.g., RBD, S1), that may elicit
    broader immune responses across several coronaviruses
  • Multivalent vaccines: As subunit vaccines only contain a small amount
    of virus genetic material, which is usually synthetic, a multivalent
    approach could be taken to incorporate the spike of more divergent
    coronaviruses and help to elicit a broader immune response

State Of the Art