Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge.
JAMA Netw Open. 2022 Aug 1;5(8):e2226335. doi: 10.1001/jamanetworkopen.2022.26335.
Antibody responses elicited by current messenger RNA (mRNA) COVID-19 vaccines decline rapidly and require repeated boosting.
To evaluate the immunogenicity and durability of heterologous and homologous prime-boost regimens involving the adenovirus vector vaccine Ad26.COV2.S and the mRNA vaccine BNT162b2.
DESIGN, SETTING, AND PARTICIPANTS: In this cohort study at a single clinical site in Boston, Massachusetts, 68 individuals who were vaccinated at least 6 months previously with 2 immunizations of BNT162b2 were boosted with either Ad26.COV2.S or BNT162b2. Enrollment of participants occurred from August 12, 2021, to October 25, 2021, and this study involved 4 months of follow-up. Data analysis was performed from November 2021 to February 2022.
Participants who were previously vaccinated with BNT162b2 received a boost with either Ad26.COV2.S or BNT162b2.
Humoral immune responses were assessed by neutralizing, binding, and functional antibody responses for 16 weeks following the boost. CD8+ and CD4+ T-cell responses were evaluated by intracellular cytokine staining assays.
Among 68 participants who were originally vaccinated with BNT162b2 and boosted with Ad26.COV2.S (41 participants; median [range] age, 36 [23-84] years) or BNT162b2 (27 participants; median [range] age, 35 [23-76] years), 56 participants (82%) were female, 7 (10%) were Asian, 4 (6%) were Black, 4 (6%) were Hispanic or Latino, 3 (4%) were more than 1 race, and 53 (78%) were White. Both vaccines were found to be associated with increased humoral and cellular immune responses, including against SARS-CoV-2 variants of concern. BNT162b2 boosting was associated with a rapid increase of Omicron neutralizing antibodies that peaked at a median (IQR) titer of 1018 (699-1646) at week 2 and declined by 6.9-fold to a median (IQR) titer of 148 (95-266) by week 16. Ad26.COV2.S boosting was associated with increased Omicron neutralizing antibodies titers that peaked at a median (IQR) of 859 (467-1838) week 4 and declined by 2.1-fold to a median (IQR) of 403 (208-1130) by week 16.
Heterologous Ad26.COV2.S boosting was associated with durable humoral and cellular immune responses in individuals who originally received the BNT162b2 vaccine. These data suggest potential benefits of heterologous prime-boost vaccine regimens for SARS-CoV-2.
当前信使 RNA（mRNA）COVID-19 疫苗引起的抗体反应迅速下降，需要反复加强。
评估腺病毒载体疫苗 Ad26.COV2.S 和 mRNA 疫苗 BNT162b2 的异源和同源加强方案的免疫原性和持久性。
设计、地点和参与者：在马萨诸塞州波士顿的一个单一临床地点进行的这项队列研究中，68 名至少在 6 个月前接受了 2 剂 BNT162b2 疫苗接种的参与者接受了 Ad26.COV2.S 或 BNT162b2 加强针。参与者的招募时间为 2021 年 8 月 12 日至 10 月 25 日，本研究涉及 4 个月的随访。数据分析于 2021 年 11 月至 2022 年 2 月进行。
先前接种过 BNT162b2 的参与者接受了 Ad26.COV2.S 或 BNT162b2 的加强针。
在加强针接种后 16 周，通过中和、结合和功能性抗体反应评估体液免疫反应。通过细胞内细胞因子染色测定评估 CD8+和 CD4+ T 细胞反应。
在最初接种 BNT162b2 并接受 Ad26.COV2.S（41 名参与者；中位[范围]年龄，36[23-84]岁）或 BNT162b2（27 名参与者；中位[范围]年龄，35[23-76]岁）加强针的 68 名参与者中，56 名（82%）为女性，7 名（10%）为亚洲人，4 名（6%）为黑人，4 名（6%）为西班牙裔或拉丁裔，3 名（4%）为多种族，53 名（78%）为白人。两种疫苗均与体液和细胞免疫反应增强相关，包括对关注的 SARS-CoV-2 变体的反应。BNT162b2 加强针与奥密克戎中和抗体的快速增加相关，其峰值在第 2 周的中位数（IQR）滴度为 1018（699-1646），到第 16 周下降了 6.9 倍，中位数（IQR）滴度为 148（95-266）。Ad26.COV2.S 加强针与奥密克戎中和抗体滴度增加相关，其峰值在第 4 周的中位数（IQR）为 859（467-1838），到第 16 周下降了 2.1 倍，中位数（IQR）为 403（208-1130）。
在最初接受 BNT162b2 疫苗接种的个体中，异源 Ad26.COV2.S 加强针与持久的体液和细胞免疫反应相关。这些数据表明 SARS-CoV-2 的异源疫苗接种方案可能具有益处。
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