Saturation time of exposure interval for cross-neutralization response to SARS-CoV-2: Implications for vaccine dose interval
Sho Miyamoto,
Yudai Kuroda,
Takayuki Kanno,
Akira Ueno,
Nozomi Shiwa-Sudo,
Naoko Iwata-Yoshikawa,
Yusuke Sakai,
Noriyo Nagata,
Takeshi Arashiro,
Akira Ainai,
Saya Moriyama,
Noriko Kishida,
Shinji Watanabe,
Kiyoko Nojima,
Yohei Seki,
Takuo Mizukami,
Hideki Hasegawa,
Hideki Ebihara,
Shuetsu Fukushi,
Yoshimasa Takahashi,
Ken Maeda,
Tadaki Suzuki
Affiliations
Sho Miyamoto
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Yudai Kuroda
Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Takayuki Kanno
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Akira Ueno
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Nozomi Shiwa-Sudo
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Naoko Iwata-Yoshikawa
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Yusuke Sakai
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Noriyo Nagata
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Takeshi Arashiro
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Center for Surveillance, Immunization, and Epidemiologic Research, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Akira Ainai
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Saya Moriyama
Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Noriko Kishida
Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Tokyo 208-0011, Japan
Shinji Watanabe
Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Tokyo 208-0011, Japan
Kiyoko Nojima
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo 208-0011, Japan
Yohei Seki
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo 208-0011, Japan
Takuo Mizukami
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo 208-0011, Japan
Hideki Hasegawa
Center for Influenza and Respiratory Virus Research, National Institute of Infectious Diseases, Tokyo 208-0011, Japan
Hideki Ebihara
Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Shuetsu Fukushi
Department of Virology I, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Yoshimasa Takahashi
Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Ken Maeda
Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Tadaki Suzuki
Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan; Corresponding author
Summary: Evaluating the serum cross-neutralization responses after breakthrough infection with various SARS-CoV-2 variants provides valuable insight for developing variant-proof COVID-19 booster vaccines. However, fairly comparing the impact of breakthrough infections with distinct epidemic timing on cross-neutralization responses, influenced by the exposure interval between vaccination and infection, is challenging. To compare the impact of pre-Omicron to Omicron breakthrough infection, we estimated the effects on cross-neutralizing responses by the exposure interval using Bayesian hierarchical modeling. The saturation time required to generate saturated cross-neutralization responses differed by variant, with variants more antigenically distant from the ancestral strain requiring longer intervals of 2–4 months. The breadths of saturated cross-neutralization responses to Omicron lineages were comparable in pre-Omicron and Omicron breakthrough infections. Our results highlight the importance of vaccine dosage intervals of 4 months or longer, regardless of the antigenicity of the exposed antigen, to maximize the breadth of serum cross-neutralization covering SARS-CoV-2 Omicron lineages.
