Division of Infectious Diseases, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
Asia Pacific Influenza Institute, Korea University College of Medicine, Seoul, Republic of Korea.
Front Immunol. 2023 Mar 7;14:1131229. doi: 10.3389/fimmu.2023.1131229. eCollection 2023.
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.
背景：单次剂量的 Ad26.COV2.S 疫苗接种能否诱导足够的免疫尚不清楚。人们还对 Ad26.COV2.S 疫苗接种者突破性感染风险增加表示担忧。
方法：进行了一项前瞻性队列研究。参与者包括接受 Ad26.COV2.S 疫苗接种并计划接种 BNT162b2、mRNA-1273 或 Ad26.COV2.S 加强针的健康成年人。在加强针接种后 3-4 周、3 个月和 6 个月，评估参与者的 IgG 抗受体结合域（RBD）抗体滴度、中和抗体（针对野生型[WT]和奥密克戎[BA.1 和 BA.5]）滴度和 Spike 特异性干扰素-γ反应。
结果：共招募了 89 名参与者（26 名接受 BNT162b2 加强针，57 名接受 mRNA-1273 加强针，7 名接受 Ad26.COV2.S 加强针）。所有参与者在接种后 6 个月的 IgG 抗 RBD 抗体滴度均显著高于基线。接种后 3 个月，BNT162b2、mRNA-1273 和 Ad26.COV2.S 组参与者的抗 WT 中和抗体滴度分别为 359、258 和 166。与抗 WT 相比，接种后 3 个月，BNT162b2、mRNA-1273 和 Ad26.COV2.S 组参与者的抗 BA.1/BA.5 中和抗体滴度分别低 23.9/10.9 倍、16.6/7.4 倍和 13.8/7.2 倍。值得注意的是，Ad26.COV2.S 接种后，BA.1 的中和抗体滴度未被增强。BNT162b2、mRNA-1273 和 Ad26.COV2.S 组参与者分别有 53.8%、62.5%和 42.9%发生突破性感染。在发生 SARS-CoV-2 突破性感染的个体和未发生突破性感染的个体之间，体液和细胞免疫无显著差异。
结论：Ad26.COV2.S 疫苗接种在 Ad26.COV2.S 疫苗接种者中诱导了可接受的体液和细胞免疫应答。然而，对奥密克戎亚变种的中和活性可忽略不计，并且在加强针接种后 3 个月，无论疫苗类型如何，突破性感染率都非常高。需要接种含有奥密克戎变异株抗原的加强针。
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