Influenza vaccine manufacturing in Viet Nam: Report on the APACI Satellite session

Dr. Do Tuan Dat, Director of Vabiotech, provided an historical overview of government-supported programs in Vietnam to develop in-country capacity for for pandemic and seasonal human influenza vaccines. International partners (WHO, BARDA/HHS, CDC) have recently increased their support to these efforts, focused on two principle manufacturers: IVAC and Vabiotech. IVAC is currently preparing for the second of three phases of trails on its egg-based inactivated A/H5N1 pandemic vaccine to determine immunogenicity and dosing regimens in healthy adults, and is also preparing a Phase 1 clinical trial of a seasonal TIV formulation. Vabiotech completed the third phase of trials on their cell-based inactivated A/H5N1 vaccine in 2012, and the licensing application was submitted in 2013. The lack of ongoing market demand for pandemic vaccines remains a hurdle for private sector investment. However, research is continuing on improved downstream processing, cell-adapted vaccine virus strains (with adequate yields and stability, for multiple subtypes), and streamlining scale-up procedures and quality control testing methods.

Dr. Le Quynh Mai, Director of the National Influenza Center (NIC) at NIHE, presented data on genetic diversity of human seasonal influenza variants circulating in Viet Nam, and discussed how the NIC contributes to global surveillance networks. She highlighted the differences between influenza epidemiology in the tropics versus temperate regions, with the presence of 2 annual peaks in transmission, suggesting the need for further research on optimal timing of vaccination. She also discussed divergence between circulating human seasonal strains and WHO recommended vaccines, in particular for the H3 and influenza B components.

Dr. Than Xuan Hanh from Navetco and Dr. Le Thanh Hoa from IBT presented on poultry vaccines for highly pathogenic H5 subtype viruses. Navetco’s egg-based inactivated NIBRG-14 vaccine (“Navet-vifluvac”) uses a master seed originally prepared at the National Institute for Biological Standards and Control (NIBSC) in the UK. Animal challenge experiments conducted at NCVD indicate that Navet-Vifluvac protects against H5 HA viruses of Clades 1; 1.1; 2.3.2.1a; 2.3.2.1c; and 2.3.4.4 (H5N6). Navet-Vifluvac was first licensed in 2012, and to date over 200 million doses have been used in Vietnam (in chickens, ducks, and quails). Dr Hoa reviewed the principle of genetic manipulation of viral genomes using the 8-plasmid system, and government initiatives for the development of biotechnology capacity. To date, however, no licensed human or veterinary vaccine products in Vietnam have used master seeds generated in country.

Dr Jan Hendriks presented the WHO Global Action Plan (GAP), with a specific focus on efforts to promote pandemic vaccine production in low- and middle-income countries through capacity building and technology transfer. Establishing and maintaining a sustainable influenza vaccine manufacturing facility is a huge challenge, requiring both stable market demand and ‘policy coherence’ from government to promote appropriate regulatory oversight and industrial development. Dr Hendriks discussed previous WHO/OIE/FAO consultations on the feasibility of cross-sectoral One Health collaboration on vaccine production, however this faces significant regulatory and economic obstacles (i.e. an insufficient business case, price differentials), and major differences in downstream processing requirements. Dr Hendriks noted Vietnam’s significant strides in strengthening the National Regulatory Authority (NRA) that oversees commercial licensing of human biologicals, with a recent WHO assessment certifying the NRA as being close to fully competent to evaluate novel formulations. This will open the door for Vietnamese vaccine producers to apply for WHO pre-qualification of their products for potential supply to UN procurement agencies.

Dr Do Huu Dung from DAH moderated a lively discussion on issues such as: Is there sufficient justification for Vietnam to produce human seasonal flu vaccines (i.e. will it ever be cost-effective or competitive)? Are Vietnamese viruses sufficiently well represented within WHO vaccine strain selection procedures? Have vaccine manufacturers within Vietnam filed for patent use of reverse genetics methodology, and have intellectual property rights been adequately transferred? Is there evidence that Rg vaccines for poultry provide comparable efficacy to classical whole virus vaccines? Are there any bivalent formulations for AIV vaccines in the pipeline, and if not, what are the obstacles? In addition, participants commented on the importance and complexity of matching vaccine strains to contemporary field variants, a common challenge for both human and veterinary vaccines.

Participants agreed that two hours was not enough! Follow-up discussions were suggested, including a future meeting focused exclusively on veterinary vaccine issues, in order to better define technical gaps, and identify methods to streamline and accelerate the licensure of updated formulations.

Prepared by Juliet Bryant, Oxford University Clinical Research Unit, with thanks to APACI organizers for supporting and coordinating this satellite session.