Is seasonal vaccination a contributing factor to the selection of influenza epidemic variants?

ABSTRACT

Influenza A/H3N2 viruses are the most common and virulent subtypes for humans. Antigenic drift, changes in antigenicity through the accumulation of mutations in the hemagglutinin (HA) gene is chiefly responsible for the continuing circulation of A/H3N2 viruses, resulting in frequent updates of vaccine strains based on new variant analyses. In humans, these drift-related mutations are considered to be primarily caused by the immune pressure elicited by natural infection. Whether or not the immune pressure elicited by vaccination (vaccine pressure) can have a certain effect on drift-related mutations is unclear. Recently, our findings suggested the possible effect of vaccine pressure on HA mutations by directly comparing amino acid differences from the corresponding vaccine strains between isolates from vaccinated and unvaccinated patients. It is possible that influenza vaccine pressure selects variants genetically distant from the vaccine strains. Considering the effect of vaccine pressure on HA mutations would contribute to further understanding the mechanism of antigenic drift, which would be helpful for predicting future epidemic viruses.

KEYWORDS:

• antigenic drift
• hemagglutinin
• mutationInfluenza
• vaccination
• vaccine pressure

Disclosure of potential conflicts of interest

The authors indicate no potential conflicts of interest.

Acknowledgments

We thank Kenjiro Shirane, Shinya Matsumoto, and Nozomi Noda for their technical support. We also thank Hiroyuki Sasaki and Donchon Kang for their support on our study.⁸

We thank the following doctors for participating in our study⁸: Shunsuke Akimitsu, Masaaki Chinen, Ken-ichi Doniwa, Keisuke Egashira, Yasuhiko Hirata, Miki Hirata, Nobuo Hirotsu, Tsuneo Inoue, Norio Iwaki, Kyosuke Kaji, Seizaburo Kashiwagi, Naoki Kawai, Takashi Kawashima, Kunio Kondo, Hiroko Kondo, Haruo Kuroki, Woon Joo Lee, Tetsunari Maeda, Koji Maehara, Tsuyoshi Makino, Shinro Matsuura, Akiko Miyata, Masashi Miyazaki, Kouichi Mochizuki, Kazuo Mori, Atsuko Nabeshima, Shin Nagao, Masatoshi Nakao, Kiyoshi Nishikawa, Yoshinori Nishimoto, Tadahiko Ogasawara, Jun Ogawa, Kaoru Oguchi, Yasuo Ontachi, Ietaka Sato, Yasuo Sato, Keigo Shibao, Kunihisa Shimomura, Shizuo Shindo, Kotoko Sumimoto, Yoshio Takasaki, Takeshi Tana, Osame Tanaka, Yuriko Tarukawa, Noriko Tateno, Keita Tatsushima, Satuki Tomita, Hiroaki Tomori, Hiroshi Ukai, Yutaka Wakasa, Masahiro Yaekashiwa, Norio Yamaguchi, Hareaki Yamamoto, Yasuhito Yamanishi, Yuji Yamashita, Satoshi Yamauchi, Takashi Yokoyama, Takato Yokoyama, Gen Yoshida, Hiroyuki Yoshimine, and Midori Yoshimura.

Funding

Our study⁸ was supported by a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (26461505 to Y.C.).