Riou Catherine, Bhiman Jinal N, Ganga Yashica, Sawry Shobna, Ayres Frances, Baguma Richard, Balla Sashkia R, Benede Ntombi, Bernstein Mallory, Besethi Asiphe S, Cele Sandile, Crowther Carol, Dhar Mrinmayee, Geyer Sohair, Gill Katherine, Grifoni Alba, Hermanus Tandile, Kaldine Haajira, Keeton Roanne S, Kgagudi Prudence, Khan Khadija, Lazarus Erica, Roux Jean Le, Lustig Gila, Madzivhandila Mashudu, Magugu Siyabulela Fj, Makhado Zanele, Manamela Nelia P, Mkhize Qiniso, Mosala Paballo, Motlou Thopisang P, Mutavhatsindi Hygon, Mzindle Nonkululeko B, Nana Anusha, Nesamari Rofhiwa, Ngomti Amkele, Nkayi Anathi A, Nkosi Thandeka P, Omondi Millicent A, Panchia Ravindre, Patel Faeezah, Sette Alessandro, Singh Upasna, van Graan Strauss, Venter Elizabeth M, Walters Avril, Moyo-Gwete Thandeka, Richardson Simone I, Garrett Nigel, Rees Helen, Bekker Linda-Gail, Gray Glenda, Burgers Wendy A, Sigal Alex, Moore Penny L, Fairlie Lee
Institute of Infectious Disease and Molecular Medicine, Division of Medical Virology, Department of Pathology, University of Cape Town, Observatory, South Africa.
Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory, South Africa.
medRxiv. 2023 Nov 20:2023.11.20.23298785. doi: 10.1101/2023.11.20.23298785.
We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection.
A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated.
No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting.
In the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost.
South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841.
South African Medical Research Council (SAMRC) and South African Department of Health (SA DoH).
我们在一项开放标签的2期试验中报告了部分剂量和全剂量的Ad26.COV2.S及BNT162b2的安全性和免疫原性，该试验的参与者此前已接种过一剂Ad26.COV2.S，其中91.4%的人有既往感染过严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的证据。
在接种Ad26.COV2.S首剂疫苗4个月后，共招募了286名成年人（有或无人类免疫缺陷病毒[HIV]），并按1:1:1:1随机分组，分别接受全剂量或半剂量的Ad26.COV2.S或BNT162b2疫苗加强针。在加强针接种后的基线、2周、12周和24周评估B细胞反应（结合、中和及抗体依赖性细胞毒性-ADCC）以及刺突特异性T细胞反应。还评估了针对Ad26载体的抗体和T细胞免疫。
未记录到与疫苗相关的严重不良事件。全剂量和半剂量的BNT162b2均提高了抗SARS-CoV-2结合抗体水平（分别提高了3.9倍和4.5倍）以及中和抗体水平（分别提高了4.4倍和10倍）。半剂量Ad26.COV2.S接种后的结合抗体和中和抗体未得到显著提高。全剂量Ad26.COV2.S未提高结合抗体水平，但略微增强了中和抗体（提高了2.1倍）。仅在全剂量BNT162b2接种后，ADCC略有增加。T细胞反应与中和抗体呈现相似模式。加强针接种6个月后，抗体和T细胞反应已降至基线水平。虽然我们检测到了强烈的抗载体免疫，但Ad26.COV2.S接种者的抗载体免疫与Ad26.COV2.S加强针接种后的刺突特异性中和抗体或T细胞反应之间无相关性。
在混合免疫的背景下，与同源Ad26.COV2.S相比，接种异源全剂量或半剂量BNT162b2 mRNA疫苗在接种后2周显示出更强的免疫原性，不过在加强针接种12周后迅速减弱。
南非国家临床试验注册中心（SANCR）：DOH-27-012022-7841。
南非医学研究理事会（SAMRC）和南非卫生部（SA DoH）。
