BBIBP-CorV和Ad26.COV2.S新冠疫苗异源与同源初免-加强免疫方案的免疫原性和安全性：在马达加斯加和莫桑比克进行的一项多中心、随机、观察者盲法非劣效性试验

Immunogenicity and Safety of Heterologous Versus Homologous Prime-Boost Regimens With BBIBP-CorV and Ad26.COV2.S COVID-19 Vaccines: A Multicentric, Randomized, Observer-Blinded Non-inferiority Trial in Madagascar and Mozambique.

作者信息

Ramgi Patrícia, Siribie Mohamadou, Rakotozandrindrainy Njariharinjakamampionona, Bule Odete, Shrivastava Harshvardhan, Chambule Lígia, Park Eun Lyeong, Fernando Carina, Boque Jéssica, Macuiana Rezelda, Razafimanantsoa Ravomialisoa, Rakotozandrindrainy Ndrainaharimira, Razafindrabe Tsiriniaina J L, Rakotoarisoa Antenaina N, Raminosoa Tiana M, Derandrainy Herinirina L, Rakotoson Masinirina M, de Silva Cynthia S S, Mutombene Mirna, Massinga Carmélia, Langa José P, Guarnacci Tobin, Kang Sophie S Y, Jo Sue Kyoung, Jeon Hyon Jin, Excler Jean-Louis, Yang Yunkai, Wang Shiyu, Sugimoto Jonathan D, Yang Jae Seung, Shim Byoung-Shik, Binger Tabea, Capitine Igor U, Aziz Asma B, Park Ju Yeon, Kim Deok Ryun, Rakotozandrindrainy Raphaël, Jani Ilesh V, Tadesse Birkneh Tilahun, Marks Florian

机构信息

Instituto Nacional de Saúde, Maputo, Mozambique.

International Vaccine Institute, Seoul, Republic of Korea.

出版信息

Clin Infect Dis. 2025 Jul 22;80(Supplement_1):S37-S46. doi: 10.1093/cid/ciaf130.

DOI:10.1093/cid/ciaf130

PMID:40694514

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12282515/

Abstract

BACKGROUND

Data on immunogenicity and safety of heterologous prime-boost (HePB) regimens using the BBIBP-CorV and Ad26.COV2.S have not yet been reported in sub-Saharan Africa.

METHODS

We conducted a randomized, observer-blinded, non-inferiority trial assessing the immunogenicity and safety of HePB regimens using BBIBP-CorV and Ad26.COV2.S, in adults aged 18-65 years. Participants enrolled, were stratified by baseline severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serostatus, and randomized into four arms in a 1:1:1:1 ratio: A1 (BBIBP-CorV, Ad26.COV2.S), A2 (BBIBP-CorV, BBIBP-CorV), B1 (Ad26.COV2.S, BBIBP-CorV), and B2 (placebo, Ad26.COV2.S), administered at 28-day intervals. Fifteen participants in each arm were randomized separately in the immunology subset at a ratio of 1:1:1:1. Primary endpoints were the geometric mean titers (GMTs) of anti-SARS-CoV-2 neutralizing antibodies (nAbs) against SARS-CoV-2 Omicron variant BA.1 and safety at 4 weeks after second vaccination. The non-inferiority margin was 0.67 fold difference in geometric mean ratio (GMR) between the ratio of GMTs in the heterologous versus corresponding homologous arms.

RESULTS

A total of 369 participants were randomized, and 367 of them received at least one dose of vaccine. Participants were between 18 and 65 years of age. Four weeks after second dose, GMT of nAbs in arms A1 and A2 was 802.7 (95% confidence interval [CI]: 635.3-1014.3) and 202.6 (95% CI: 150.8-272.1), respectively, with an adjusted GMR of 4.2 (2-sided 95% CI: 2.9-5.9). GMTs were 603.6 (95% CI: 446.1-816.7) and 725.7 (95% CI: 539.5-976.1) in arms B1 and B2, respectively, with an adjusted GMR of 0.8 (2-sided 95% CI: .5-1.2). Three serious adverse events were reported and none of them were related to the vaccination.

CONCLUSIONS

The noninferiority criterion was met only in arm A1 versus A2. HePB regimens were safe and well tolerated.

CLINICAL TRIALS REGISTRATION

NCT04998240.

摘要

背景

在撒哈拉以南非洲地区，尚未有关于使用BBIBP-CorV和Ad26.COV2.S进行异源初免-加强（HePB）方案的免疫原性和安全性的数据报道。

方法

我们开展了一项随机、观察者盲法、非劣效性试验，评估在18至65岁成年人中使用BBIBP-CorV和Ad26.COV2.S进行HePB方案的免疫原性和安全性。纳入的参与者根据基线严重急性呼吸综合征冠状病毒2（SARS-CoV-2）血清学状态进行分层，并以1:1:1:1的比例随机分为四组：A1组（BBIBP-CorV，Ad26.COV2.S）、A2组（BBIBP-CorV，BBIBP-CorV）、B1组（Ad26.COV2.S，BBIBP-CorV）和B2组（安慰剂，Ad26.COV2.S），每隔28天给药一次。每组15名参与者在免疫学亚组中以1:1:1:1的比例单独随机分组。主要终点是针对SARS-CoV-2奥密克戎变异株BA.1的抗SARS-CoV-2中和抗体（nAbs）的几何平均滴度（GMTs）以及第二次接种疫苗后4周的安全性。非劣效性界值为异源组与相应同源组GMTs比值的几何平均比（GMR）相差0.67倍。

结果

共有369名参与者被随机分组，其中367人接受了至少一剂疫苗。参与者年龄在18至65岁之间。第二次给药后4周，A1组和A2组nAbs的GMT分别为802.7（95%置信区间[CI]：635.3 - 1014.3）和202.6（95%CI：150.8 - 272.1），调整后的GMR为4.2（双侧95%CI：2.9 - 5.9）。B1组和B2组的GMT分别为603.6（95%CI：446.1 - 816.7）和725.7（95%CI：539.5 - 976.1），调整后的GMR为0.8（双侧95%CI：0.5 - 1.2）。报告了3例严重不良事件，均与疫苗接种无关。