[Title]
Enhanced antibody responses in fully vaccinated individuals against pan-SARS-CoV-2 variants following Omicron breakthrough infection

[Author] 
Hye Won Jeong ^1 2 12, Se-Mi Kim ^3 12, Min Kyung Jung ^4 12, Ji Yun Noh ^5 12, Ji-Seung Yoo ^3 12, Eun-Ha Kim ¹, Young-Il Kim ³, Kwangmin Yu ¹, Seung-Gyu Jang ^1 3, Juryeon Gil ¹, Mark Anthony Casel ^1 3, Rollon Rare ^1 3, Jeong Ho Choi ¹, Hee-Sung Kim ^1 2, Jun Hyoung Kim ², Jihye Um ⁶, Chaeyoon Kim ⁴, Yeonjae Kim ⁷, Bum Sik Chin ⁷, Sungmin Jung ⁸, Jun Yong Choi ⁹, Kyoung-Ho Song ¹⁰, Yong-Dae Kim ^1 11, Jun-Sun Park ⁶, Joon Young Song ⁵, Eui-Cheol Shin ^4 8, Young Ki Choi ^1 3 13

¹ College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 28644, Republic of Korea

² Department of Internal Medicine, Chungbuk National University Hospital, Cheongju 28644, Republic of Korea

³ Center for Study of Emerging and Re-emerging Viruses, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea

⁴ The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon 34126, Republic of Korea

⁵ Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul 08308, Republic of Korea

⁶ Public Health Research Institute, National Medical Center, Seoul 04564, Republic of Korea

⁷ Division of Infectious Diseases, Department of Internal Medicine, National Medical Center, Seoul 04564, Republic of Korea

⁸ Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea

⁹ Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

¹⁰Division of Infectious Diseases, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Republic of Korea

¹¹ Chungbuk Regional Cancer Center, Chungbuk National University Hospital, Cheongju 28644, Republic of Korea

[Journal] 
Cell Reports Medicine, Volume 3, Issue 10, 18 October 2022, 100764

[Abstract]

Omicron has become the globally dominant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, creating additional challenges due to its ability to evade neutralization. Here, we report that neutralizing antibodies against Omicron variants are undetected following COVID-19 infection with ancestral or past SARS-CoV-2 variant viruses or after two-dose mRNA vaccination. Compared with two-dose vaccination, a three-dose vaccination course induces broad neutralizing antibody responses with improved durability against different SARS-CoV-2 variants, although neutralizing antibody titers against Omicron remain low. Intriguingly, among individuals with three-dose vaccination, Omicron breakthrough infection substantially augments serum neutralizing activity against a broad spectrum of SARS-CoV-2 variants, including Omicron variants BA.1, BA.2, and BA.5. Additionally, after Omicron breakthrough infection, memory T cells respond to the spike proteins of both ancestral and Omicron SARS-CoV-2 by producing cytokines with polyfunctionality. These results suggest that Omicron breakthrough infection following three-dose mRNA vaccination induces pan-SARS-CoV-2 immunity that may protect against emerging SARS-CoV-2 variants of concern.