Cell Rep Med . Enhanced antibody responses in fully vaccinated individuals against pan-SARS-CoV-2 variants following Omicron breakthrough infection

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Cell Rep Med


. 2022 Sep 19;100764.
doi: 10.1016/j.xcrm.2022.100764. Online ahead of print.
Enhanced antibody responses in fully vaccinated individuals against pan-SARS-CoV-2 variants following Omicron breakthrough infection


Hye Won Jeong ¹ , Se-Mi Kim ² , Min Kyung Jung ³ , Ji Yun Noh ⁴ , Ji-Seung Yoo ² , Eun-Ha Kim ⁵ , Young-Il Kim ² , Kwangmin Yu ⁵ , Seung-Gyu Jang ⁶ , Juryeon Gil ⁵ , Mark Anthony Casel ⁶ , Rollon Rare ⁶ , Jeong Ho Choi ⁵ , Hee-Sung Kim ¹ , Jun Hyoung Kim ⁷ , Jihye Um ⁸ , Chaeyoon Kim ³ , Yeonjae Kim ⁹ , Bum Sik Chin ⁹ , Sungmin Jung ¹⁰ , Jun Yong Choi ¹¹ , Kyoung-Ho Song ¹² , Yong-Dae Kim ¹³ , Jun-Sun Park ⁸ , Joon Young Song ¹⁴ , Eui-Cheol Shin ¹⁵ , Young Ki Choi ¹⁶



Affiliations

• PMID: 36182684
• DOI: 10.1016/j.xcrm.2022.100764

Free article

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.

Keywords: D614G; Omicron BA.1; Omicron BA.2; SARS-CoV-2; T cell immune response; ancestral; breakthrough infection; cross-neutralization; mRNA vaccine; recovered patient; variants of concern.