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, Kwangmin Yu, Seung Gyu Jang, Juryeon Gil, Mark Anthony Casel, Rollon Rare, Jeong Ho Choi, Hee Sung Kim, Jun Hyoung Kim, Jihye Um, Chaeyoon Kim, Yeonjae Kim, Bum Sik Chin, Sungmin JungJun Yong Choi, Kyoung Ho Song, Yong Dae Kim, Jun Sun Park, Joon Young Song, Eui Cheol Shin, Young Ki Choi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number100764
JournalCell Reports Medicine
Volume3
Issue number10
DOIs
StatePublished - 18 Oct 2022
Externally publishedYes

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

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