Update on the assessment and authorisation of veterinary vaccines

Why is it necessary to vaccinate against animal diseases?

Vaccination generally helps to:

• reduce the risk of transmission within the same species and to other species, including humans, and therefore the risk of a pandemic;
• limit animal suffering caused by the disease, which can lead to high mortality on farms;
• safeguard the agricultural economy and adequate food supplies by avoiding massive disease-related losses in livestock animals.

What are the types of vaccines available?

There are three main vaccine technologies:

• live attenuated vaccines: these contain a weakened version of the pathogen, which multiplies in the recipient organism but has lost its pathogenicity;
• inactivated vaccines: the pathogen used is completely inactivated; it no longer reproduces, which prevents any pathogenicity;
• vaccines derived from platform technologies: unlike traditional vaccines, these use a fragment of genetic material or a protein specific to the pathogen, rather than all of its genetic material. mRNA vaccines fall into this category.

Note that the category of autogenous vaccines (or autovaccines) is governed by specific legislation, as they can only be prepared from a pathogen isolated from a given farm for use on that same farm.

What are platform-based vaccines and what are their advantages?

The concept of a vaccine platform refers to a standardised methodology that always uses the same basic components to produce a vaccine in industrial quantities. It can be rapidly adapted to be effective against different pathogens, by inserting new genetic or protein sequences.

For example, one common platform technology involves using a virus that reproduces easily but is not pathogenic to the species for which vaccines are commonly developed, in order to mass-produce the protein that will make up the vaccine once purified. This is the case, for example, with baculoviruses, which only affect invertebrates. 

Self-replicating mRNA vaccines are another of these platform technologies. The vaccine consists of an incomplete fragment of the pathogen's RNA combined with a mechanism that allows it to enter cells.

These technologies offer a number of advantages, as they can:

• respond more quickly to emerging threats by adapting the fragment of genetic material that triggers immunity in the host.
• be used to develop diagnostic techniques capable of differentiating between vaccinated and unvaccinated animals, which is crucial in the fight against animal epidemics. This is possible with platform-based vaccines because vaccinated animals develop antibodies only against the protein encoded by the RNA used in the vaccine. It is therefore possible to determine whether animals have been infected by testing their reaction to other proteins in the pathogen. In particular, this prevents pathogenic viruses from multiplying at a low level without being detected through the presence of symptoms in the animals.

How are veterinary vaccines assessed?

Veterinary vaccines are subject to the same stringent requirements as human vaccines. They are assessed according to three main criteria:

• Quality: to guarantee that the vaccine has been manufactured under standardised, reproducible and optimal conditions;
• Safety: to ensure that the vaccine poses no risk to the animals receiving it or the humans consuming the vaccinated animals or their products (milk, eggs, etc.);
• Efficacy: to confirm that it provides effective protection against the disease.

Vaccines intended for livestock species are unique in that they are used on animals whose products (milk, eggs, meat, offal, etc.) are consumed by humans. A further step in the assessment is added with an in-depth evaluation to guarantee the safety of the vaccine for people consuming these products. This means that every component of the vaccine, whether the active ingredient or any adjuvants and excipients, is carefully checked to ensure that it poses no risk when an animal product is consumed.

What are temporary authorisations for use and why are they needed?

In the event of a health emergency and pending the granting of a full marketing authorisation (MA), certain vaccines may be covered by a temporary authorisation for use. The requirements for these vaccines to be safe and harmless remain just as strict, both for the vaccinated animal and for the consumer. On the other hand, evidence of their efficacy can be obtained on the basis of studies involving fewer animals than for traditional MA applications.

How is the safety of veterinary vaccines for consumers assessed?

Generally speaking, the safety assessment of vaccines via animal products includes assessments of the safety of:

• adjuvants and excipients, verifying that they belong to lists of substances recognised as safe for humans;
• active ingredients (pathogen, portion of genetic material or immunogenic protein derived from the pathogen), focusing on the specific features associated with the type of vaccine concerned, as detailed in the quality and safety section of the authorisation dossier.

Specific features associated with the different types of vaccines:

• Attenuated and inactivated vaccines: the assessment takes into account and verifies the fact that attenuation or inactivation of the pathogen has resulted in a stable vaccine that has no possibility of reactivating a virulent germ, for the animal species for which the vaccine is intended.
• Viral vaccine platform technologies: the assessment takes into account and verifies the absence of pathogenicity to animals or humans of the pathogen used as the vector, as well as the quality of the filtration that guarantees the absence of vector virus in the vaccine.
• mRNA vaccines: the assessment takes into account and confirms through the dossier supplied that:
  • since the mRNA is only a fragment of the genetic material, it can never become a complete virus again;
  • the mRNA is by nature unstable and degrades rapidly (which is why mRNA-based vaccines are generally transported and stored in extremely cold conditions);
  • the mRNA does not penetrate the nucleus of cells, which means it cannot interact with the DNA of animals or humans or insert itself into their genome;
  • when a product from a vaccinated animal is consumed, any residual mRNA is destroyed in the stomach by digestive enzymes and acidic conditions.

Moreover, RNA, the basic component of animal and plant cells, is a basic constituent of our food.

Besides the initial authorisation, pharmaceutical companies are subject to regular inspections by the ANMV, in order to ensure that vaccines are manufactured in accordance with the application dossier and standards of good manufacturing practice for veterinary medicines.