WHO informal consultation on characterization and quality aspect of vaccines based on live viral vectors, December 2003
Live viral vectors provide an effective means for heterologous antigen expression in vivo and thus represent promising platforms for developing novel vaccines. While preclinical evaluation of live viral vectors has indicated their potential for immunization purposes, there is as yet limited clinical experience of their efficacy and safety. With increasing numbers of viral vectors now entering clinical trials, an urgent need to establish appropriate regulatory requirements to ensure their quality, safety and efficacy, has been recognized.
Key aspects of the development, production, quality control as well as nonclinical and clinical evaluation of vaccines based on live, viral vectors were considered in this global forum of regulators, vaccine developers, and academic experts. Discussion was focused on chimeric live flavivirus vectors, poxvirus vectors, adenovirus vectors, and alphavirus replicon vectors as candidate vaccines.
Current requirements for the production, control, nonclinical testing and clinical trials were presented by several National Regulatory Authorities (EU, USA, China, Canada) and issues for further considerations were recommended by the Consultation. Although several guidance documents provide general principles which apply to vaccines based on viral vectors, a need was identified for specific guidelines related to vectored vaccines.
Scientific issues of critical importance for further development of vectored vaccines were identified. Further investigations were recommended on the following issues: the potential for recombination of vectored vaccines with wild type pathogenic strains; implications of prior infections on the immunogenicity of vectored vaccines; the genetic stability of replicating vectors in vitro and in vivo and the potential for reversion to virulence; potential changes of vector tropism; and tests for replication competent virus in vaccine lots. In addition, a number of specific issues related to particular vectored vaccine are identified throughout the report.
Public acceptance of vectored vaccines was considered as a challenge for further development of these novel products and a need for a forum to discuss concerns and to communicate the views of leading experts in this area to the general public was identified. WHO was requested to coordinate the next steps to take this forward.
The Consultation recommended that WHO publishes the detailed meeting report as a first step towards the development of the WHO guidelines. This meeting report has been presented to the Expert Committee on Biological Standardization at its meeting in 2004 to obtain advice on the way forward.