Selection of antigenically advanced variants of seasonal influenza viruses
Abstract
Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014?2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.
- Chengjun Li1 n1
- , Masato Hatta1 n1
- , David F. Burke2, 3 n1
- , Jihui Ping1 n1
- , Ying Zhang1 n1
- , Makoto Ozawa1, 4
- , Andrew S. Taft1
- , Subash C. Das1
- , Anthony P. Hanson1
- , Jiasheng Song1
- , Masaki Imai1, 5
- , Peter R. Wilker1
- , Tokiko Watanabe6
- , Shinji Watanabe6
- , Mutsumi Ito7
- , Kiyoko Iwatsuki-Horimoto7
- , Colin A. Russell3, 8, 9
- , Sarah L. James2, 3
- , Eugene Skepner2, 3
- , Eileen A. Maher1
- , Gabriele Neumann1
- , Alexander I. Klimov10 n2
- , Anne Kelso11
- , John McCauley12
- , Dayan Wang13
- , Yuelong Shu13
- , Takato Odagiri14
- , Masato Tashiro14
- , Xiyan Xu10
- , David E. Wentworth10
- , Jacqueline M. Katz10
- , Nancy J. Cox10
- , Derek J. Smith2, 3, 15
- & Yoshihiro Kawaoka1, 4, 6, 7
Abstract
Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014?2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.