Abstract
The embryonated egg-based platform currently produces the majority of seasonal influenza vaccines by employing a well-developed master donor virus (MDV, A/PR/8/34 (PR8)) to generate high-growth reassortants (HGRs) for A/H1N1 and A/H3N2 subtypes. Although the egg-based platform can supply enough seasonal influenza vaccines, it cannot meet surging demands during influenza pandemics. Therefore, multi-purpose platforms are desirable for pandemic preparedness. The Vero cell-based production platform is widely used for human vaccines and could be a potential multi-purpose platform for pandemic influenza vaccines. However, many wild-type and egg-derived influenza viruses cannot grow efficiently in Vero cells. Therefore, it is critical to develop Vero cell-derived high-growth MDVs for pandemic preparedness. In this study, we evaluated two in-house MDVs (Vero-15 and VB5) and two external MDVs (PR8 and PR8-HY) to generate Vero cell-derived HGRs for five avian influenza viruses (AIVs) with pandemic potentials (H5N1 clade 2.3.4, H5N1 clade 2.3.2.1, American-lineage H5N2, H7N9 first wave and H7N9 fifth wave). Overall, no single MDV could generate HGRs for all five AIVs, but this goal could be achieved by employing two in-house MDVs (vB5 and Vero-15). In immunization studies, mice received two doses of Vero cell-derived inactivated H5N1 and H7N9 whole virus antigens adjuvanted with alum and developed robust antibody responses.
Highlights
Vaccine supply for unpredictable pandemics is a challenge
The PB2-S360Y mutation has been confirmed to enhance the activity of viral RNA-dependent RNA polymerase in MDCK cells [15], so it may enhance the virus growth in Vero cells
Could generate high-growth reassortants (HGRs) for RG6, RG30, and RG56B; MDV PR8-National Institute for Biological Standards and Control (NIBSC) could generate HGRs for RG30 and R3. These results indicate that multiple MDVs may be a better choice for generating Vero cell-derived HGRs and we could use the two in-house MDVs (Vero-15 and vB5) to generate Vero cell-derived HGRs for all five subtypes of avian influenza viruses (AIVs)
Summary
For the supply of influenza vaccines, there is a conflict between the demand of seasonal and pandemic vaccines. The egg-based platform is widely used and could provide enough seasonal influenza vaccines, but it is hard to meet a surging demand during pandemics because of the long production time [1]. The other two platforms could produce influenza vaccines in a short time, which accelerates vaccine production and increases vaccine supply during pandemics [2]. These two platforms are used in a limited number of countries with low market share of seasonal vaccines (about 10–15% in the USA) [3]. Multi-purpose platforms are desirable for pandemic preparedness [4]
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