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Coronaviruses roadmap:
Vaccines

Research roadmap for coronavirus vaccine development

Download 202402 Draft Coronavirus Vaccine research roadmap Final

5

DNA/RNA vaccines

Dependencies

Next steps

DNA/RNA vaccines

Research Question

  • Develop nucleic acid-based vaccines that are efficacious, safe and
    usable in animal production systems, whilst establishing cost effective
    mechanisms for product delivery

Research Gaps and Challenges

  • Mucosal immunity: DNA/RNA vaccines typically induce systemic
    immunity, but their ability to generate strong mucosal immunity
    remains limited. This is critical for respiratory and gastrointestinal
    coronaviruses in animals
  • Cold chain maintenance: Currently mRNA vaccines, in particular,
    require stringent cold chain conditions, which complicates distribution
    in remote or field conditions, especially problematic for livestock and
    wildlife
  • Affordability: Despite their high efficacy, RNA and DNA vaccines may
    be more expensive to produce and distribute, particularly in lowincome regions or for large-scale animal vaccination campaigns, as has been seen for COVID-19 access at a global level.
    Sterilizing immunity: Related to the mucosal immunity, there is
    uncertainty over whether these vaccines can induce sterilizing
    immunity. Will non-sterilizing immunity will be enough to control viral transmission in large herd/flocks etc?
  • Breadth of immunity: mRNA vaccines tend to be species-specific,
    raising questions about their ability to protect across different animal
    species
  • Response to variants: While DNA and RNA vaccines can be quickly
    updated to target new variants, it remains a challenge to predict how
    new variants will emerge and escape immune responses, although this
    is true of all vaccines
  • Public perception: Public opinion on the safety and efficacy of novel
    vaccine platforms (DNA/RNA) remains mixed, especially in agriculture, where concerns about the safety of animal products from vaccinated animals can affect acceptance

Solution Routes

  • Non-sterilizing immunity: Research should investigate how non-sterilizing immunity driven by DNA/RNA vaccines could impact immune selection and recombination of viral variants, as well as its role in disease control
  • Alternative administration routes: Investigating alternative routes of
    administration, such as aerosolized RNA vaccines, may enhance
    mucosal immunity and provide better protection at the sites of viral
    entry
  • Broadening immunity: DNA vaccines may offer broader immunity
    across species. Studies should explore how these and mRNA vaccines
    can be utilized in different hosts to create cross-protective immunity
  • Vaccine-therapeutic combinations: Testing the combination of
    vaccines with therapeutic agents (e.g., antiviral drugs or immunomodulators) could improve outcomes by enhancing immune
    responses and viral clearance
  • Antigen selection for mRNA vaccines: Research is needed to
    determine the best combinations of antigens (e.g., spike, nucleocapsid)
    to include in DNA/RNA vaccines, aiming to elicit a balanced T-cell and
    antibody response
  • Investigating immune tolerance: The increasing IgG4 levels observed
    with multiple mRNA doses suggests the possibility of immunotolerance, which should be further investigated to ensure long-term efficacy of these vaccines
  • T-cell responses: Studies are required to assess how DNA/RNA vaccines induce long-lasting T-cell responses, which are critical for durable protection and viral clearance
  • Maternal immunity: The role of maternal immunity should be explored in developing vaccination plans for production systems with animals of different ages, particularly in livestock where passive immunity from mother to offspring is important
  • Public education campaigns: To address concerns around DNA/RNA
    vaccines, educational campaigns should focus on the safety and
    efficacy of these platforms, particularly in the context of safe animal
    products entering the food chain

Dependencies

  • Vaccine administration strategies: A comprehensive vaccine
    administration plan must account for vaccine durability, animal age,
    and the type of production system to optimize outcomes across
    species
  • Public communication plans: Clear communication strategies are
    needed to improve public acceptability of products from vaccinated
    animals, addressing concerns about safety and marketability
  • Emergency financing and commitment: Investments are required to
    ensure vaccines are produced and available for immediate use during
    variant emergencies, with commitments from governments and
    organizations to purchase vaccines in the event of outbreaks in
    affected animals
  • Regulatory acceleration: Regulatory pathways need to be streamlined
    to allow for the rapid approval and deployment of new vaccines in the
    event of emerging variants, similar to what was done during the
    COVID-19 pandemic

State Of the Art

  • mRNA vaccines: mRNA vaccines have demonstrated efficacy in humans (e.g., COVID-19) but are generally species-specific, which raises challenges in developing cross-species vaccines for animals. However, the speed of R&D during the COVID-19 pandemic showed that these platforms could be rapidly adapted in emergencies
  • T-cell responses: The majority of studies on DNA/RNA vaccines have
    shown relatively low T-cell responses, which may limit their ability to
    provide long-term protection without further optimization
  • Immune tolerance: There is emerging evidence that repeated mRNA
    vaccinations increase IgG4 levels, suggesting the possibility of immune
    tolerance, which could reduce vaccine effectiveness over time. This
    phenomenon warrants further study