Abstract
Background: The immune profile against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by Omicron in individuals with various immune histories. Methods: The neutralization susceptibility of the variants, including Omicron and their ancestors, was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections of Alpha/Delta with multiple time intervals following vaccination. Findings: Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against Omicron was induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies. Conclusions: Immune histories with breakthrough infections can overcome the resistance to infection by Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against Omicron and future variants. Funding: This study was supported by grants from the Japan Agency for Medical Research and Development (AMED).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 249-261.e4 |
| Journal | Med |
| Volume | 3 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 8 2022 |
Keywords
- BNT162b2 mRNA vaccine
- COVID-19 vaccine
- Omicron variant
- SARS-CoV-2
- Translation to patients
- breakthrough infection
- neutralizing antibody
ASJC Scopus subject areas
- Medicine(all)
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Vaccination-infection interval determines cross-neutralization potency to SARS-CoV-2 Omicron after breakthrough infection by other variants. / Miyamoto, Sho; Arashiro, Takeshi; Adachi, Yu et al.
In: Med, Vol. 3, No. 4, 08.04.2022, p. 249-261.e4.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Vaccination-infection interval determines cross-neutralization potency to SARS-CoV-2 Omicron after breakthrough infection by other variants
AU - Miyamoto, Sho
AU - Arashiro, Takeshi
AU - Adachi, Yu
AU - Moriyama, Saya
AU - Kinoshita, Hitomi
AU - Kanno, Takayuki
AU - Saito, Shinji
AU - Katano, Harutaka
AU - Iida, Shun
AU - Ainai, Akira
AU - Kotaki, Ryutaro
AU - Yamada, Souichi
AU - Kuroda, Yudai
AU - Yamamoto, Tsukasa
AU - Ishijima, Keita
AU - Park, Eun Sil
AU - Inoue, Yusuke
AU - Kaku, Yoshihiro
AU - Tobiume, Minoru
AU - Iwata-Yoshikawa, Naoko
AU - Shiwa-Sudo, Nozomi
AU - Tokunaga, Kenzo
AU - Ozono, Seiya
AU - Hemmi, Takuya
AU - Ueno, Akira
AU - Kishida, Noriko
AU - Watanabe, Shinji
AU - Nojima, Kiyoko
AU - Seki, Yohei
AU - Mizukami, Takuo
AU - Hasegawa, Hideki
AU - Ebihara, Hideki
AU - Maeda, Ken
AU - Fukushi, Shuetsu
AU - Takahashi, Yoshimasa
AU - Suzuki, Tadaki
N1 - Funding Information: This work was supported in part by grants from the Japan Agency for Medical Research and Development (AMED) (grant numbers JP21fk0108104, JP20fk0108534, and JP21fk0108615). We thank Miki Akimoto, Aya Sato, Dai Izawa, Yusuke Sakai, Noriyo Nagata, Akiko Sataka, Asato Kojima, Izumi Kobayashi, Yuki Iwamoto, Yuko Sato, Milagros Virhuez Mendoza, Noriko Nakajima, Kenta Takahashi, Yuichiro Hirata, Masataka Tokita, Masanori Isogawa, Kazutaka Terahara, Takayuki Matsumura, Tomohiro Takano, Taishi Onodera, Eriko Izumiyama, Akira Dosaka, Kazuko Isoyama, Naoka Yoshida, Rieko Iwaki, and Emi Koda at NIID for their technical support and Fukumi Nakamura-Uchiyama at Tokyo Metropolitan Bokutoh Hospital and Hidefumi Shimizu at JCHO Tokyo Shinjuku Medical Center for collection of blood samples from vaccinees. We also thank the following healthcare facilities, local health centers, and public health institutes for their contribution in providing us with valuable patient information and samples on breakthrough cases: Aki Health Center, Akiru Municipal Medical Center, Atsugi City Hospital, Akita Research Center for Public Health and Environment, Aomori Jikeikai Hospital, Aso Onsen Hospital, Chiba City Institute of Health and Environment, Chiba Prefectural Institute of Public Health, Chigasaki City Public Health Center, Chuhoku Branch Office for Public Health and Welfare, Daiwa Hospital (Osaka), Fukui Prefectural Institute of Public Health and Environmental Science, Fujimino Emergency Hospital, Fukuoka City Hospital, Gifu City Public Health Center, Gifu Prefectural General Medical Center, Gifu Prefectural Research Institute for Health and Environmental Sciences, Gunma Prefectural Institute of Public Health and Environmental Sciences, Gunma Saiseikai Maebashi Hospital, Hachioji City Public Health Center, Hakodate City Institute of Public Health, Hakodate Public Health Center, Harada Hospital (Hiroshima), Hyogo Prefectural Institute of Public Health Science, Ikegami General Hospital, IMS Fujimi General Hospital, IMS Sapporo Digestive Disease Center General Hospital, Inba Health and Welfare Center, International Goodwill Hospital, International University of Health and Welfare Hospital, International University of Health and Welfare Mita Hospital, Ishikawa Prefectural Central Hospital, Ishikawa Prefecture Health and Welfare Department, Ishikawa Prefectural Institute of Public Health and Environmental Science, Itami City Hospital, Japanese Red Cross Gifu Hospital, Japanese Red Cross Kanazawa Hospital, Japanese Red Cross Kumamoto Hospital, Japanese Red Cross Narita Hospital, JCHO Kanazawa Hospital, JCHO Nankai Medical Center, JCHO Takanawa Hospital, Juntendo University Hospital, Kaga Medical Center, Kameda Medical Center, Kasai Clinic (Osaka), Kashiwa Public Health Center, Kawachi General Hospital, Kawaguchi Seiwa Hospital, Keio University Hospital, Keiwakai Ebetsu Hospital, Kitakyushu Public Health Center, Kitakyushu Public Health Institute, Kitasato University Kitasato Institute Hospital, Kobe City Nishi-Kobe Medical Center, Kobe Ekisaikai Hospital, Komatsu Municipal Hospital, Koriyama City Public Health Center, Kumamoto City Hospital, Kumamoto City Public Health Center, Kumamoto Prefectural Institute of Public-Health and Environmental Science, Kurume-shi Public Health Center, Kyoritsu Narashinodai Hospital, Kyoto City Institute of Health and Environmental Sciences, Kyoto Kujo Hospital, Kyoto Prefectural Institute of Public Health and Environment, Kyowakai Kyoritsu Hospital, Maebashi-shi Public Health Center, Makita General Hospital, Matsui Hospital (Tokyo), Matsumoto City Public Health Center, Mie Prefectunal Institute of Public Health and Environmental Sciences, Minami Kaga Health and Welfare Center, Minoh City Hospital, Misato Kenwa Hospital, Mitsui Memorial Hospital, Mizushima Kyodo Hospital, Nadogaya Hospital, Nagano City Public Health Center, Nagano City Public Health Institute, Nagano Environmental Conservation Research Institute, Nagasaki Prefecture Iki Hospital, Nagayama Hospital (Osaka), Nanbu Tokushukai Hospital, Nanshu Orthopedics Hospital, Narita Tomisato Tokushukai Hospital, National Center for Global Health and Medicine, National Hospital Organization Kyoto Medical Center, National Hospital Organization Osaka National Hospital, National Hospital Organization Nagoya Medical Center, Niigata City Health Center, Niigata Prefectural Institute of Public Health and Environmental Sciences, Nippon Medical School Chiba Hokusoh Hospital, Nishinomiya City Public Health Center, Nitta ENT clinic, Obihiro Dai-ichi Hospital, Obihiro Health Center, Oita City Public Health Center, Oita Kouseiren Tsurumi Hospital, Oita Prefectural Institute of Health and Environment, Okayama Kyoritsu Hospital, Osaka Medical and Pharmaceutical University Hospital, Saiseikai Kanazawa Hospital, Saiseikai Moriyama Municipal Hospital, Saiseikai Yamaguchi Hospital, Saitama City Hospital, Saitama Nishi Kyodo Hospital, Sakura General Hospital (Aichi), Sakura Hospital (Kumamoto), Sapporo Public Health Office, Sasebo City General Hospital, Shibuya Clinic (Ishikawa), Shimane Prefectural Institute of Public Health and Environmental Science, Shimonoseki City Hospital, Shimonoseki Public Health Center, Shin Komonji Hospital, Shin-Yamanote Hospital, Shonan Daiichi Hospital, Suginami Public Health Center, Sumida Ward Public Health Center, Takasaki General Public Health Center, Tama Nambu Chiiki Hospital, Tamashima Central Hospital, Tochigi Prefectural Institute of Public Health and Environmental Science, Tokyo Medical and Dental University Medical Hospital, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo Metropolitan Institute of Public Health, Tokyo Women’|'s Medical University Adachi Medical Center, Tonan Hospital, Tsuchiya General Hospital, Tsukuba Central Hospital, Tsurukawa Sanatorium Hospital, Ueda Health and Welfare Office, Utsunomiya City Institute of Public Health and Environment, and Yamanashi Prefectural Institute for Public Health and Environment. We also thank GISAID for the platform to share and compare our data with data submitted globally. Conceptualization, S.F. Y.T. and T.S.; methodology, S. Miyamoto, T.A. S.F. Y.A. S. Moriyama, H. Kinoshita, K.M. H. Katano, and S.I.; investigation, S. Miyamoto, T.A. Y.A. S. Moriyama, H. Kinoshita, T.K. S.S. A.A. R.K. S.Y. Y. Kuroda, T.Y. K.I. E.-S.P. Y.I. Y. Kaku, M.T. H. Katano, S.I. N.I.-Y. N.S.-S. K.T. S.O. T.H. A.U. N.K. S.W. K.N. Y.S. T.M. and K.M.; writing – original draft, S. Miyamoto, T.A. Y.A. S. Moriyama, H. Kinoshita, S.F. Y.T. and T.S.; writing – review & editing, S. Miyamoto, T.A. Y.A. S. Moriyama, H. Kinoshita, T.K. S.S. H. Katano, S.I. A.A. R.K. S.Y. Y. Kuroda, T.Y. K.I. E.-S.P. Y.I. Y. Kaku, M.T. N.I.-Y. N.S.-S. K.T. S.O. T.H. A.U. N.K. S.W. K.N. Y.S. T.M. H.H. H.E. K.M. S.F. Y.T. and T.S.; visualization, S. Miyamoto; supervision, H.H. H.E. K.M. S.F. Y.T. and T.S.; project administration, S.F. Y.T. and T.S.; funding acquisition, K.M. Y.T. and T.S. S. Miyamoto performed statistical analyses. S.F. Y.T. and T.S. had unrestricted access to all data. S. Miyamoto, T.A. Y.A. S. Moriyama, H. Kinoshita, S.F. Y.T. and T.S. prepared the first draft of the manuscript, which was reviewed and edited by all other authors. All authors agreed to submit the manuscript, read and approved the final draft, and take full responsibility of its content including the accuracy of the data and statistical analysis. The authors declare no competing interests. Funding Information: This work was supported in part by grants from the Japan Agency for Medical Research and Development (AMED) (grant numbers JP21fk0108104 , JP20fk0108534 , and JP21fk0108615 ). We thank Miki Akimoto, Aya Sato, Dai Izawa, Yusuke Sakai, Noriyo Nagata, Akiko Sataka, Asato Kojima, Izumi Kobayashi, Yuki Iwamoto, Yuko Sato, Milagros Virhuez Mendoza, Noriko Nakajima, Kenta Takahashi, Yuichiro Hirata, Masataka Tokita, Masanori Isogawa, Kazutaka Terahara, Takayuki Matsumura, Tomohiro Takano, Taishi Onodera, Eriko Izumiyama, Akira Dosaka, Kazuko Isoyama, Naoka Yoshida, Rieko Iwaki, and Emi Koda at NIID for their technical support and Fukumi Nakamura-Uchiyama at Tokyo Metropolitan Bokutoh Hospital and Hidefumi Shimizu at JCHO Tokyo Shinjuku Medical Center for collection of blood samples from vaccinees. We also thank the following healthcare facilities, local health centers, and public health institutes for their contribution in providing us with valuable patient information and samples on breakthrough cases: Aki Health Center, Akiru Municipal Medical Center, Atsugi City Hospital, Akita Research Center for Public Health and Environment, Aomori Jikeikai Hospital, Aso Onsen Hospital, Chiba City Institute of Health and Environment, Chiba Prefectural Institute of Public Health, Chigasaki City Public Health Center, Chuhoku Branch Office for Public Health and Welfare, Daiwa Hospital (Osaka), Fukui Prefectural Institute of Public Health and Environmental Science, Fujimino Emergency Hospital, Fukuoka City Hospital, Gifu City Public Health Center, Gifu Prefectural General Medical Center, Gifu Prefectural Research Institute for Health and Environmental Sciences, Gunma Prefectural Institute of Public Health and Environmental Sciences, Gunma Saiseikai Maebashi Hospital, Hachioji City Public Health Center, Hakodate City Institute of Public Health, Hakodate Public Health Center, Harada Hospital (Hiroshima), Hyogo Prefectural Institute of Public Health Science, Ikegami General Hospital, IMS Fujimi General Hospital, IMS Sapporo Digestive Disease Center General Hospital, Inba Health and Welfare Center, International Goodwill Hospital, International University of Health and Welfare Hospital, International University of Health and Welfare Mita Hospital, Ishikawa Prefectural Central Hospital, Ishikawa Prefecture Health and Welfare Department, Ishikawa Prefectural Institute of Public Health and Environmental Science, Itami City Hospital, Japanese Red Cross Gifu Hospital, Japanese Red Cross Kanazawa Hospital, Japanese Red Cross Kumamoto Hospital, Japanese Red Cross Narita Hospital, JCHO Kanazawa Hospital, JCHO Nankai Medical Center, JCHO Takanawa Hospital, Juntendo University Hospital, Kaga Medical Center, Kameda Medical Center, Kasai Clinic (Osaka), Kashiwa Public Health Center, Kawachi General Hospital, Kawaguchi Seiwa Hospital, Keio University Hospital, Keiwakai Ebetsu Hospital, Kitakyushu Public Health Center, Kitakyushu Public Health Institute, Kitasato University Kitasato Institute Hospital, Kobe City Nishi-Kobe Medical Center, Kobe Ekisaikai Hospital, Komatsu Municipal Hospital, Koriyama City Public Health Center, Kumamoto City Hospital, Kumamoto City Public Health Center, Kumamoto Prefectural Institute of Public-Health and Environmental Science, Kurume-shi Public Health Center, Kyoritsu Narashinodai Hospital, Kyoto City Institute of Health and Environmental Sciences, Kyoto Kujo Hospital, Kyoto Prefectural Institute of Public Health and Environment, Kyowakai Kyoritsu Hospital, Maebashi-shi Public Health Center, Makita General Hospital, Matsui Hospital (Tokyo), Matsumoto City Public Health Center, Mie Prefectunal Institute of Public Health and Environmental Sciences, Minami Kaga Health and Welfare Center, Minoh City Hospital, Misato Kenwa Hospital, Mitsui Memorial Hospital, Mizushima Kyodo Hospital, Nadogaya Hospital, Nagano City Public Health Center, Nagano City Public Health Institute, Nagano Environmental Conservation Research Institute, Nagasaki Prefecture Iki Hospital, Nagayama Hospital (Osaka), Nanbu Tokushukai Hospital, Nanshu Orthopedics Hospital, Narita Tomisato Tokushukai Hospital, National Center for Global Health and Medicine, National Hospital Organization Kyoto Medical Center, National Hospital Organization Osaka National Hospital, National Hospital Organization Nagoya Medical Center, Niigata City Health Center, Niigata Prefectural Institute of Public Health and Environmental Sciences, Nippon Medical School Chiba Hokusoh Hospital, Nishinomiya City Public Health Center, Nitta ENT clinic, Obihiro Dai-ichi Hospital, Obihiro Health Center, Oita City Public Health Center, Oita Kouseiren Tsurumi Hospital, Oita Prefectural Institute of Health and Environment, Okayama Kyoritsu Hospital, Osaka Medical and Pharmaceutical University Hospital, Saiseikai Kanazawa Hospital, Saiseikai Moriyama Municipal Hospital, Saiseikai Yamaguchi Hospital, Saitama City Hospital, Saitama Nishi Kyodo Hospital, Sakura General Hospital (Aichi), Sakura Hospital (Kumamoto), Sapporo Public Health Office, Sasebo City General Hospital, Shibuya Clinic (Ishikawa), Shimane Prefectural Institute of Public Health and Environmental Science, Shimonoseki City Hospital, Shimonoseki Public Health Center, Shin Komonji Hospital, Shin-Yamanote Hospital, Shonan Daiichi Hospital, Suginami Public Health Center, Sumida Ward Public Health Center, Takasaki General Public Health Center, Tama Nambu Chiiki Hospital, Tamashima Central Hospital, Tochigi Prefectural Institute of Public Health and Environmental Science, Tokyo Medical and Dental University Medical Hospital, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo Metropolitan Institute of Public Health, Tokyo Women’|'s Medical University Adachi Medical Center, Tonan Hospital, Tsuchiya General Hospital, Tsukuba Central Hospital, Tsurukawa Sanatorium Hospital, Ueda Health and Welfare Office, Utsunomiya City Institute of Public Health and Environment, and Yamanashi Prefectural Institute for Public Health and Environment. We also thank GISAID for the platform to share and compare our data with data submitted globally. Publisher Copyright: © 2022 Elsevier Inc.
PY - 2022/4/8
Y1 - 2022/4/8
N2 - Background: The immune profile against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by Omicron in individuals with various immune histories. Methods: The neutralization susceptibility of the variants, including Omicron and their ancestors, was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections of Alpha/Delta with multiple time intervals following vaccination. Findings: Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against Omicron was induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies. Conclusions: Immune histories with breakthrough infections can overcome the resistance to infection by Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against Omicron and future variants. Funding: This study was supported by grants from the Japan Agency for Medical Research and Development (AMED).
AB - Background: The immune profile against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by Omicron in individuals with various immune histories. Methods: The neutralization susceptibility of the variants, including Omicron and their ancestors, was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections of Alpha/Delta with multiple time intervals following vaccination. Findings: Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against Omicron was induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies. Conclusions: Immune histories with breakthrough infections can overcome the resistance to infection by Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against Omicron and future variants. Funding: This study was supported by grants from the Japan Agency for Medical Research and Development (AMED).
KW - BNT162b2 mRNA vaccine
KW - COVID-19 vaccine
KW - Omicron variant
KW - SARS-CoV-2
KW - Translation to patients
KW - breakthrough infection
KW - neutralizing antibody
UR - http://www.scopus.com/inward/record.url?scp=85127386112&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85127386112&partnerID=8YFLogxK
U2 - 10.1016/j.medj.2022.02.006
DO - 10.1016/j.medj.2022.02.006
M3 - Article
AN - SCOPUS:85127386112
SN - 2666-6359
VL - 3
SP - 249-261.e4
JO - Med
JF - Med
IS - 4
ER -