Enhanced antibody responses in fully vaccinated individuals against pan-SARS-CoV-2 variants following Omicron breakthrough infection
Hye Won Jeong, Se‐Mi Kim, Min Kyung Jung, Ji Yun Noh, Ji‐Seung Yoo, Eun-Ha Kim, Young‐Il Kim, Kwang-Min Yu, Seung‐Gyu Jang, Juryeon Gil, Mark Anthony B. Casel, Rollon Rare, Jeong Ho Choi, Hee‐Sung Kim, Jun Hyoung Kim, Jihye Um, Chaeyoon Kim, Yeonjae Kim, Bum Sik Chin, Sungmin Jung, Jun Yong Choi, Kyoung‐Ho Song, Yong‐Dae Kim, Jun-Sun Park, Joon Young Song, Eui‐Cheol Shin, Young Ki Choi
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.