VAC2VAC is working on new methods of testing batches of vaccines that don’t involve animal models.
Every single batch of vaccines that is manufactured must undergo a series of rigorous tests to ensure it meets certain standards. The tests, which are used for human and animal vaccines, are designed to ensure that each batch of vaccines is both safe (e.g. it is free of impurities such as toxins that could cause an adverse reaction) and potent (i.e. that the vaccines will trigger a protective response from the immune system).
Today, many of these batch tests involve large numbers of laboratory animals. Apart from the pain and distress that this causes to the animals and the ethical questions it poses, the process tends to be slow, expensive and sometimes of questionable relevance and reproducibility. Replacing animal tests with better alternatives would therefore not only be more ethical and affordable, but would also speed up the testing process so that vaccine batches will be available for vaccination faster.
IMI’s VAC2VAC project is developing new methods for testing vaccine batches that do not involve animals. In an interview with the IMI Programme Office, the consortium explains what VAC2VAC is aiming to do, and what it has achieved so far.
What is the aim of the project?
VAC2VAC, which has 23 partners across 8 European countries, is developing in vitro test methods that can be used to confirm that a batch of vaccines that just rolled off the production line is consistent with and of the same quality as a previously quality-controlled batch, and to identify sub-standard batches. VAC2VAC tackles both vaccine quality and animal welfare. It will allow us to move away from the traditional paradigm of batch release testing for some vaccines (which relies heavily on animal tests) and to accelerate the introduction of the new paradigm of consistency testing, based on innovative, non-animal techniques.
What kinds of models are you developing?
VAC2VAC focuses on the development of non-animal tests for the quality control testing of vaccines and to replace animal-based methods still in place.
No new animal models are being developed. Instead, the focus of VAC2VAC is on replacement by looking at the integrity of the vaccine components and the quality of the antigen(s), as well as parameters linked to the biological function of the vaccine (i.e. its ability to induce a protective immune response) and vaccine safety (i.e. the absence of toxicity) using cell-based assays.
What have you achieved so far?
One highlight concerns a test for a vaccine against tick-borne encephalitis virus (TBEV). TBEV infections can result in severe disease with sometimes permanent neurological complications, yet a highly effective vaccine is available. In VAC2VAC, we have further developed the monocyte activation test (MAT), a cell-based assay to replace a rabbit test for pyrogens (contaminants that could cause a fever). The MAT was optimised for the TBEV vaccine by the Italian Istituto Superiore di Sanità (ISS), and the collaboration between the industry and ISS in the VAC2VAC consortium led to a publication in ALTEX, a scientific journal focused on alternatives to animal experimentation. The method was validated in GSK, the manufacturer of the vaccine, in 2019, and it was implemented in July 2020 after approval by the competent authorities. This is the first method within VAC2VAC to reach regulatory acceptance and implementation and thus represents an important milestone in our effort to implement the consistency approach. The approval of the MAT by the competent authorities shows that successful collaboration with regulatory national agencies has been instrumental in VAC2VAC.
We are also making progress on tests to assess the quantity and quality of antigens in a vaccine – antigens are a key component of the vaccine as they trigger the immune response.
For example, immunochemical methods such as the enzyme-immunosorbent assay (ELISA) could be used to demonstrate vaccine quality and batch to batch consistency and may lead to the replacement of animal tests used for the determination of vaccine potency. Progress has been made in the development of ELISAs for tick-borne encephalitis virus (TBEV), rabies, Clostridium chauvoei, and diphtheria, tetanus and acellular pertussis vaccines.
In addition, we are establishing a set of physicochemical methods to determine the qualitative and quantitative profile of vaccine antigens. Mass spectrometry assays are being developed for leptospira and diphtheria, tetanus and acellular pertussis (DTaP) and monovalent veterinary tetanus vaccines.
Has anything surprised you so far in the project?
The support gathered across the world, namely outside of Europe. This was particularly evident during the International Alliance for Biological Standardization (IABS) and VAC2VAC global congress 2019, in which case studies on specific vaccines were presented and discussed both from low and middle-income countries (LMIC) as well as developed economies, highlighting the global interest and commitment towards the replacement of in vivo (animal) testing. Participants from developing countries clearly voiced their need for more information, training, and support in building case studies and generating the scientific evidence needed for the transition to alternative methods.
All the participants, from developed and LMIC economies, agreed on the need for a pragmatic approach to global regulatory harmonisation, with one of the key recommendations being that World Health Organization (WHO) and World Organisation for Animal Health (OIE) should openly reference in vitro testing in their regulatory documents, a move that would significantly advance the development and implementation of alternative methods globally and promote regulatory harmonisation.