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Vet Advice: mRNA transforms science behind vaccine development

Vaccination is one of the major success stories in human and veterinary medicine. Modern vaccines reshaped approaches to animal health and production medicine. On the human side, vaccines greatly reduced the incidence of infectious diseases such as polio, and were instrumental in eradicating, on a global scale, killer diseases such as human smallpox and rinderpest in ruminants.

Conventional vaccine development has not been as effective against rapidly evolving pathogens such as influenza, or emerging viral diseases such as Ebola or Zika. Although conventional attenuated and killed virus vaccines shaped spectacular medical victories, stability, speed of onset, duration of immunity and breadth of cross-protection to different serotypes or strains were shortfalls.

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SARS-CoV-2, the agent implicated in the ongoing COVID-19 pandemic, pried doors open for a new generation of vaccine development, the newest being messenger RNA (mRNA) technology.

Until recently, there were four main types of vaccines:

  1. Live attenuated vaccines composed of a weakened form of a target pathogen.
  2. Inactivated vaccines composed of killed organisms that stimulate immunity against target pathogens.
  3. Subunit, recombinant, polysaccharide and conjugate vaccines. Through sophisticated biotechnological mechanics, such as recombinant DNA technology, pieces of DNA or bacterial sugars (polysaccharides) are inserted into bacterial and mammalian cells. Altered cells, as they grow, direct antigen production that stimulates protective immunity against a pathogen.
  4. Toxoid vaccines that produce protective immunity against harmful toxins e.g. tetanus toxoid.

COVID-19 and other highly infectious diseases threaten food and economic security. Animal pandemics readily distort trade in animal and animal products and undermine agriculture development in poor countries. Global pandemics escalate into food shortages, political disorder and economic uncertainty. Globalization and climate change increase the likelihood of new patterns of emergence and spread of human and livestock viruses.

The desire for new and improved vaccines is acute. Risks associated with transboundary spread of highly infectious diseases such as foot-and-mouth disease (FMD) are pre-eminent wherever swine and cattle are raised. There isn’t a livestock producer anywhere that doesn’t flinch when FMD’s effect is discussed. Everyone realizes that even developed countries with sophisticated agriculture systems are susceptible.

The effort to produce a safe and effective vaccine for COVID-19 moves ahead at full throttle. Benefits will surely spill into the livestock sector. Despite its urgency, experts agree a vaccine is a year or more down the road. Researchers at the Karolinska Institute in Stockholm recognize that vaccine distribution needs to be worldwide. Scaling production to more than seven billion doses is daunting in the extreme. Access to rapid and accurate diagnostic testing and enhanced traceability capability aided by artificial intelligence technology (e.g. smart phones) is crucial — tools already recognized as key elements in animal disease control efforts.

Professor Bekeredjian-Ding of Germany’s Paul Ehrlich Institute makes the following comments about the mRNA technology platform:

“mRNA vaccines against infectious diseases are new. Much of the research to date on mRNA vaccines is related to cancer prophylaxis and treatment. An mRNA vaccine has never been registered for infectious disease.

“Parts of disease-causing organisms or the proteins they produce of traditional vaccines are introduced into the body to provoke the immune system in mounting a response. In contrast, mRNA vaccines trick the body into producing its own viral protein directed by an mRNA template placed in cells. The body then produces antibodies against the protein generated onboard. To produce mRNA vaccines, scientists construct synthetic versions of the mRNA using computers and modern laboratory methods. mRNA segments are then injected into the body and become incorporated into cells. Cells transcribe the introduced mRNA and produce copies of viral protein. The immune system detects the foreign protein and mounts a defensive response using both the acquired and innate immune systems, the latter typically stimulated by adjuvants (immune stimulants) in traditional vaccines. As such, mRNA vaccines produce a second layer of protection without adjuvants and the immune response is very strong.

“Because mRNA vaccines eliminate time-limiting steps in the manufacturing processes, they become easier and quicker to produce than traditional vaccines. Upscaling production is much easier, a critical component when manufacturing billions of doses.

“Most vaccines in use need to be transported and stored in an uninterrupted cold-chain process. mRNA vaccines are more thermostable (e.g. freeze-dried mRNA vaccine has been shown to be stable between 5 C and 25 C for up to 36 months). Beyond shorter manufacturing times, mRNA vaccines are potentially more effective and represent novel therapeutic options for major diseases such as cancer. The absence of infectious elements enhances the safety factor for patients. Production of mRNA vaccines is laboratory based, easily standardized and potentially scaled, allowing quick responses to large outbreaks and epidemics.

“A major advantage of mRNA vaccines is that RNA can be produced in the laboratory from a DNA template using readily available materials, less expensively and faster than conventional vaccine production, which can require the use of chicken eggs or other mammalian cells.”

Bekeredjian-Ding adds the optimal route for vaccine delivery isn’t yet known, but some potential options for mRNA vaccine could include needle-free intradermal methods, nasal sprays, or injections into the muscle, blood or lymph nodes.

Although mRNA vaccine technology has not been extensively tested, preclinical and early clinical trials show promise using animal models. Research on mRNA technology is about to expand exponentially. The ship has already sailed.

— Dr. Ron Clarke prepares this column on behalf of the Western Canadian Association of Bovine Practitioners. Suggestions for future articles can be sent to Canadian Cattlemen or to the WCABP.

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Dr. Ron Clarke

Dr. Ron Clarke prepares this column on behalf of the Western Canadian Association of Bovine Practitioners. Suggestions for future articles can be sent to Canadian Cattlemen ([email protected]) or WCABP ([email protected]).

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