Research roadmap for coronavirus vaccine development

Subunit vaccines

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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

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

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

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

Subunit vaccines have been developed and licensed for other animal
pathogens, for example the Hendra virus G subunit vaccine for use in
horses (EquiVac)
An S-based subunit vaccine has been described for use in piglets
against porcine deltacoronavirus (PDCoV) : A novel recombinant Sbased subunit vaccine induces protective immunity against porcine
deltacoronavirus challenge in piglets | Journal of Virology (asm.org)
Subunit vaccines of either full-length spike, S1 or RBD have been shown to experimentally elicit antibody responses in experimental animal models, against SARS-CoV-1, MERS, SARS-CoV-2 and other human CoVs (mice, hamsters, palm civet, rhesus macaque) Frontiers | Subunit Vaccines Against Emerging Pathogenic Human Coronaviruses
(frontiersin.org)
Cross neutralisation of human and civet SARS-CoV variants has been
seen, induced by S RBD-subunit vaccines. Cross-Neutralization of
Human and Palm Civet Severe Acute Respiratory Syndrome
Coronaviruses by Antibodies Targeting the Receptor-Binding Domain of Spike Protein | The Journal of Immunology | American Association of Immunologists (aai.org)