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. 2023 Mar 7:14:1131229.
doi: 10.3389/fimmu.2023.1131229. eCollection 2023.

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

Hakjun Hyun  1   2   3 , A-Yeung Jang  1 , Heedo Park  4 , Jung Yeon Heo  5 , Yu Bin Seo  6 , Eliel Nham  1   2   3 , Jin Gu Yoon  1   2   3 , Hye Seong  1   2   3 , Ji Yun Noh  1   2   3 , Hee Jin Cheong  1   2   3 , Woo Joo Kim  1   2   3 , Soo-Young Yoon  7 , Jong Hyeon Seok  4 , Jineui Kim  4 , Man-Seong Park  3   4 , Joon Young Song  1   2   3
Affiliations

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

Hakjun Hyun et al. Front Immunol. .

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.

Keywords: COVID-19; SARS-CoV-2; booster; breakthrough infection; cellular immunity; humoral immunity; vaccines.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study flowchart. Abbreviation: IgG, immunoglobulin G; RBD, receptor binding domain; WT, wild type.
Figure 2
Figure 2
Humoral immune responses after booster vaccination. GMTs of IgG anti-RBD antibodies (A), ND50 against wild type virus (B), and ND50 against Omicron BA.1 (C). Blood samples were collected at baseline (day of booster dose, T0), 3–4 weeks post-booster dose (T1), 3 months post-booster dose (T2), and 6 months post-booster dose (T3). The black bar represents GMT with 95% confidence intervals. Abbreviation: NS, not significant; IgG, immunoglobulin G; GMT, geometric mean titer; RBD, receptor binding domain; ND50, 50% neutralization dose.
Figure 3
Figure 3
Comparisons of neutralizing activities against wild type, Omicron BA.1, and Omicron BA.5 viruses at 3 months after booster vaccination. The black bar represents GMT with 95% confidence intervals. NS, not significant; ND50, 50% neutralization dose; GMT, geometric mean titer.
Figure 4
Figure 4
Cellular immune response after booster vaccination. (A) SARS-CoV-2 original spike protein-specific interferon-γ release assay. (B) SARS-CoV-2 variant spike protein-specific interferon-γ release assay. Blood samples were collected at baseline (day of booster dose, T0), 3–4 weeks post-booster dose (T1), 3 months post-booster dose (T2), and 6 months post-booster dose (T3). The black bar represents median with interquartile range. NS, not significant; S, spike; IFN- γ, interferon gamma.
Figure 5
Figure 5
Comparisons of humoral immunity between SARS-CoV-2-uninfected and -infected participants among mRNA vaccine-boosted group. GMTs of IgG anti-RBD antibodies (A), and ND50 against wild type and Omicron BA.1 viruses (B). Blood samples were collected at baseline (day of booster dose, T0), 3–4 weeks post-booster dose (T1), 3 months post-booster dose (T2), and 6 months post-booster dose (T3). The black bar represents GMT with 95% confidence intervals. NS, not significant; IgG, immunoglobulin G; GMT, geometric mean titer; RBD, receptor binding domain; ND50, 50% neutralization dose.
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References

    1. Bartsch YC, Tong X, Kang J, Avendaño MJ, Serrano EF, García-Salum T, et al. . Omicron variant spike-specific antibody binding and fc activity are preserved in recipients of mRNA or inactivated COVID-19 vaccines. Sci Transl Med (2022) 14:eabn9243. doi: 10.1126/scitranslmed.abn9243 - DOI - PMC - PubMed
    1. Cox RJ, Brokstad KA. Not just antibodies: B cells and T cells mediate immunity to COVID-19. Nat Rev Immunol (2020) 20:581–2. doi: 10.1038/s41577-020-00436-4 - DOI - PMC - PubMed
    1. Sette A, Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell (2021) 184:861–80. doi: 10.1016/j.cell.2021.01.007 - DOI - PMC - PubMed
    1. Jackson CB, Farzan M, Chen B, Choe H. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol (2022) 23:3–20. doi: 10.1038/s41580-021-00418-x - DOI - PMC - PubMed
    1. Lipsitch M, Krammer F, Regev-Yochay G, Lustig Y, Balicer RD. SARS-CoV-2 breakthrough infections in vaccinated individuals: Measurement, causes and impact. Nat Rev Immunol (2022) 22:57–65. doi: 10.1038/s41577-021-00662-4 - DOI - PMC - PubMed

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