1. A virus-like particle vaccination strategy expands its tolerance to H3N2 antigenic drift by enhancing neutralizing antibodies against hemagglutinin stalk
- Author
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Yu-Chih Yang, Chia-Ying Wu, Chih-Yuan Chen, Fu-Ting Wu, Ji-Rong Yang, Chao-Hua Lin, Ming-Tsan Liu, Chieh-Yu Cheng, Hsiang-Yi Huang, Chuan-Yi Kuo, and Pei-Wen Hsiao
- Subjects
0301 basic medicine ,Cross Protection ,viruses ,Taiwan ,Hemagglutinin (influenza) ,Hemagglutinin Glycoproteins, Influenza Virus ,Biology ,Antibodies, Viral ,complex mixtures ,Antigenic drift ,Virus ,Microbiology ,03 medical and health sciences ,Influenza A Virus, H1N1 Subtype ,0302 clinical medicine ,Virus-like particle ,Virology ,Influenza, Human ,Humans ,Vaccines, Virus-Like Particle ,030212 general & internal medicine ,Original antigenic sin ,Pharmacology ,Influenza A Virus, H3N2 Subtype ,Vaccination ,virus diseases ,Hemagglutination Inhibition Tests ,Antibodies, Neutralizing ,Antigenic Variation ,030104 developmental biology ,Vaccines, Inactivated ,Immunization ,Influenza Vaccines ,Humoral immunity ,biology.protein - Abstract
Seasonal influenza viruses impact public health annually due to their continual evolution. However, the current inactivated seasonal vaccines provide poor protection against antigenically drifted viruses and require periodical reformulation through hit-and-miss predictions about which strains will circulate during the next season. To reduce the impact caused by vaccine mismatch, we investigated the drift-tolerance of virus-like particles (VLP) as an improved vaccine candidate. The cross-protective humoral immunity elicited by the H3N2-VLP vaccine constructed for the 2011-2012 season was examined against viruses isolated from 2010 to 2015 in Taiwan evolving chronologically through clades 1, 4, 5, 3B and 3C, as well as viruses that were circulating globally in 2005, 2007 and 2009. Mouse immunization results demonstrated that H3N2-VLP vaccine elicited superior immunological breadth in comparison with the cognate conventional whole-inactivated virus (WIV) vaccine. Titers of neutralizing antibodies against heterologous strains representing each epidemic period in the VLP group were significantly higher than in the WIV group, indicating the antibody repertoire induced by the H3N2-VLPs was insensitive to viral antigenic drift over a span of at least 10 years. Noticeably, H3N2-VLP elicited higher levels of anti-stalk antibodies than H3N2-WIV, which offset the ineffectiveness caused by antigenic drift. This advantageous effect was attributed to the uncleaved precursor of their HA proteins. These results suggest a mechanism through which VLP-induced humoral immunity may better tolerate the evolutionary dynamics of influenza viruses and point to the possible use of a VLP vaccine as a method by which the requirement for annual updates of seasonal influenza vaccines may be diminished.
- Published
- 2017