Humoral and cellular immunogenicity of homologous and heterologous booster vaccination in Ad26.COV2.S-primed individuals: Comparison by breakthrough infection

Hakjun Hyun, A. Yeung Jang, Heedo Park, Jung Yeon Heo, Yu Bin Seo, Eliel Nham, Jin Gu Yoon, Hye Seong, Ji Yun Noh, Hee Jin Cheong, Woo Joo Kim, Soo Young Yoon, Jong Hyeon Seok, Jineui Kim, Man Seong Park, Joon Young Song

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Background: Whether or not a single-dose Ad26.COV2.S prime and boost vaccination induces sufficient immunity is unclear. Concerns about the increased risk of breakthrough infections in the Ad26.COV2.S-primed population have also been raised. Methods: A prospective cohort study was conducted. Participants included healthy adults who were Ad26.COV2.S primed and scheduled to receive a booster vaccination with BNT162b2, mRNA-1273, or Ad26.COV2.S. The IgG anti-receptor binding domain (RBD) antibody titers, neutralizing antibody (NAb) titers (against wild type [WT] and Omicron [BA.1 and BA.5]), and Spike-specific interferon-γ responses of the participants were estimated at baseline, 3–4 weeks, 3 months, and 6 months after booster vaccination. Results: A total of 89 participants were recruited (26 boosted with BNT162b2, 57 with mRNA-1273, and 7 with Ad26.COV2.S). The IgG anti-RBD antibody titers of all participants were significantly higher at 6 months post-vaccination than at baseline. The NAb titers against WT at 3 months post-vaccination were 359, 258, and 166 in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. Compared with those against WT, the NAb titers against BA.1/BA.5 were lower by 23.9/10.9-, 16.6/7.4-, and 13.8/7.2-fold in the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively, at 3 months post-vaccination. Notably, the NAb titers against BA.1 were not boosted after Ad26.COV2.S vaccination. Breakthrough infections occurred in 53.8%, 62.5%, and 42.9% of the participants from the BNT162b2-, mRNA-1273-, and Ad26.COV2.S-boosted groups, respectively. No significant difference in humoral and cellular immunity was found between individuals with and without SARS-CoV-2 breakthrough infections. Conclusion: Booster vaccination elicited acceptable humoral and cellular immune responses in Ad26.COV2.S-primed individuals. However, the neutralizing activities against Omicron subvariants were negligible, and breakthrough infection rates were remarkably high at 3 months post-booster vaccination, irrespective of the vaccine type. A booster dose of a vaccine containing the Omicron variant antigen would be required.

Original languageEnglish
Article number1131229
JournalFrontiers in immunology
Volume14
DOIs
Publication statusPublished - 2023

Bibliographical note

Funding Information:
This study was supported by a grant from the Korea National Institute of Health, Korea Disease Control, and Prevention Agency (project number: 2021-ER2303-00).

Publisher Copyright:
Copyright © 2023 Hyun, Jang, Park, Heo, Seo, Nham, Yoon, Seong, Noh, Cheong, Kim, Yoon, Seok, Kim, Park and Song.

Keywords

  • COVID-19
  • SARS-CoV-2
  • booster
  • breakthrough infection
  • cellular immunity
  • humoral immunity
  • vaccines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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