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- Title
Balancing the influenza neuraminidase and hemagglutinin responses by exchanging the vaccine virus backbone.
- Authors
Gao, Jin; Wan, Hongquan; Li, Xing; Rakic Martinez, Mira; Klenow, Laura; Gao, Yamei; Ye, Zhiping; Daniels, Robert
- Abstract
Virions are a common antigen source for many viral vaccines. One limitation to using virions is that the antigen abundance is determined by the content of each protein in the virus. This caveat especially applies to viral-based influenza vaccines where the low abundance of the neuraminidase (NA) surface antigen remains a bottleneck for improving the NA antibody response. Our systematic analysis using recent H1N1 vaccine antigens demonstrates that the NA to hemagglutinin (HA) ratio in virions can be improved by exchanging the viral backbone internal genes, especially the segment encoding the polymerase PB1 subunit. The purified inactivated virions with higher NA content show a more spherical morphology, a shift in the balance between the HA receptor binding and NA receptor release functions, and induce a better NA inhibitory antibody response in mice. These results indicate that influenza viruses support a range of ratios for a given NA and HA pair which can be used to produce viral-based influenza vaccines with higher NA content that can elicit more balanced neutralizing antibody responses to NA and HA. Author summary: Influenza vaccines are produced on a large scale to meet the annual U.S. and global demand. To efficiently produce the required number of influenza vaccine doses, virions are commonly used as the antigen source due to their high viral protein content. A draw-back to using virions is that the final antigen composition of the vaccine is determined by the inherent properties of the vaccine virus. While this approach for influenza vaccines is beneficial for the more abundant HA antigen, it likely limits the protective response generated by the less abundant NA antigen. Our results demonstrate that the NA and HA content in vaccine viruses can be optimized by changing the internal genes of the vaccine virus, thereby preserving the surface antigens. The increase in the virion NA content that was achieved elicited higher NA antibody titres and generated more balanced neutralizing antibody responses to HA and NA. Since HA and NA neutralizing antibodies are both protective, this approach could help to improve the suboptimal efficacy of current influenza vaccines and to generate vaccines that provide broader coverage against circulating strains.
- Subjects
NEURAMINIDASE; VIRAL vaccines; FLU vaccine efficacy; VACCINE effectiveness; DNA vaccines; INFLUENZA vaccines; INFLUENZA A virus, H1N1 subtype; INFLUENZA
- Publication
PLoS Pathogens, 2021, Vol 17, Issue 4, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1009171