Research roadmap for coronavirus vaccine development

Download 202402 Draft Coronavirus Vaccine research roadmap Final

Adjuvant

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Dependencies

Next steps

4 Inactivated vaccines
4A Safety
4B Delivery route
4C Delivery platform
4D Efficacy in challenge model
5 DNA/RNA vaccines
5A Safety
5B Delivery route
5C Delivery platform
5D Efficacy in challenge model
3 Rationally attenuated candidates
3A Safety
3B Delivery route
3C Delivery platform
3D Efficacy in challenge model

Adjuvant

Research Question

What are we trying to achieve? Identify and develop optimal adjuvants that could be used in different animal models and for different vaccine platforms to enhance the immune response induced by vaccines against animal coronaviruses
What is the problem? Deciding which adjuvants are suitable in different animals, their formulation, their effectiveness, and any possible off-target effects are all factors that need to be considered when choosing a suitable adjuvant. Also, there may be a lack of suitable adjuvant (either it does not exist, or it has not been validated) for less-well characterized animal models

Research Gaps and Challenges

Mechanisms of action: Although adjuvants are widely used in vaccines to enhance the immune response, the mechanisms by which they do this has not been well characterised (i.e., we know they promote activation of PRRs/PAMPs, but not specific pathways). Therefore, there is the possibility of off-target effects, adverse reactions and nonspecific immune responses that could be triggered by adjuvants
Formulation: Many different formulations of adjuvant exist, including alum-based, oil emulsions, water-in-oil nanoemulsions, lipid nanoparticles, mineral salts, microbial products, saponins, polymers, liposomes and synthetic small molecular agonists. Deciding on the most appropriate adjuvant may then rely on biased preference or on knowledge of pre-existing usage, which may not be the most optimal adjuvant
Side effects/toxicity: Freud’s adjuvant is not licensed for use in human vaccine because of its toxicity
Specificity: Because of the lack of systemic response and immune effectiveness, it is difficult to match and design appropriate adjuvants for specific vaccines, which may pose a barrier in deciding the most suitable candidate
Licensing/approvals: If novel adjuvants are formulated, or have been less well-characterized for a specific vaccine, then getting the regulatory approvals for use in animals may provide a hurdle (cost, time). Considerations of using adjuvants that bind you with a specific organization – limits use of other adjuvants, may mean you do not have an adjuvant if that company stops making it
Longevity of immune response: Generally, adjuvanted vaccines require booster vaccinations as they do not provide long-lived immune responses. Consideration needs to me given when deciding whether repeated vaccination with this adjuvant is beneficial, or whether it can be withdrawn for safe livestock production
Adjuvants for mucosal delivery: Are there adjuvants for mucosal delivery?

Solution Routes

Monitoring: Clinical development stage of promising adjuvants should be monitored to understand what is available for use
Safety: Testing for safety in animals and animal products to understand adverse or off-target effects of adjuvants
Optimisation: Studying the optimal ratio of adjuvant required for desired impact on immune response
Longitudinal assessments: As immunity wanes over time with adjuvanted vaccines, longitudinal assessment of the generated immune response is important to understand when titres start to decline to know when boosters may be required, and it should be determined whether there is longevity in response with different adjuvants.

Dependencies

Animal models: Understanding which animals are at risk from infection by coronaviruses, and therefore will require vaccination + adjuvants
Type of antigen: Deciding what type of antigen (e.g., subunit or mRNA) and the immune response required will help with deciding which adjuvant may be more appropriate
Considerations of using a combination of adjuvants and delivery systems: To achieve higher immune activations

State Of the Art

Promising adjuvants have been tested or are testing in preclinical models. A better knowledge about mechanisms of action could result in more adjuvants entering a clinical development stage, but perhaps this is less of a problem when designing adjuvants for animal vaccines. (Castrodeza-Sanz, Javier, Iván Sanz-Muñoz, and Jose M. Eiros. “Adjuvants for COVID-19 Vaccines.” Vaccines 11.5 (2023): 902.)