WHO informal consultation on characterization and quality aspect of vaccines based on live viral vectors, December 2003
Recommendations to WHO and priorities for future work
The consultative group agreed that guidelines on production and control, nonclinical and clinical testing of vaccines based on viral vectors will be a useful tool since there are no globally accepted guidelines for preventive vectored vaccines, at present. However, it was recognized that some points are already covered in the existing guidelines published by WHO and some international bodies such as EMEA (5,3). Technical requirements and clinical trial approval processes are in place in some countries and national guidelines are being developed in some countries (EU, USA, Canada and China).
The Consultation recommended to WHO to publish a detailed meeting report which will provide points considered at the meeting and concerns raised by vaccine developers and regulators and will serve as a first step towards the development of the WHO guidelines.
The following specific concerns for vaccines based on viral vectors were identified as issues of critical importance to be investigated further:
- Potential of recombination with wild type pathogenic strains - Vector – circulating virus could create a more pathogenic strain. - This issue should be addressed in vitro or in animal studies.
- Implications of prior infections on the immunogenicity of vectored vaccines.. - Prior infection with related viruses may reduce vaccine immunogenicity (e.g., adenoviruses, poxviruses (smallpox vaccine)) - Immunogenicity of subsequent doses, especially with different gene in same vector (e.g., modified poxviruses, adenoviruses): should be addressed if relevant
- Genetic stability of replicating viruses in vivo should be studied focusing on: - The sequence insert, and known areas of attenuation - Known epitopes
- Potential changes of tropism may lead to new properties of replicating viruses and should be carefully evaluated.
- Tests for absence of reversion to virulence should be performed when an attenuated vector is used.
- The absence of replication competent virus when replication incompetent vectors are used should be demonstrated.
- Public acceptance of vectored vaccines with specific safety concerns could be an issue. A need for a forum to discuss concerns, and how best to communicate the risks and benefits of the new approach to general public was identified and WHO was requested to take a lead on it.
The Consultative group recommended to WHO to present this meeting report to the Expert Committee on Biological Standardization at its meeting in 2004 and to obtain advice on the way forward.