Chanda Chama, Kibengo Freddie, Mutua Michael, Ogada Fred, Muturi-Kioi Vincent, Akis Yildirim Belkis M, Amondi Mary, Baines Andrea, Basajja Vincent, Borthwick Nicola, Bosire Kefa, Chambula Elias, Chetty Paramesh, Chinyenze Kundai, Chirro Oscar, Crook Alison, De Bont Jan, Fernandez Natalia, Ejou Peter, Farah Bashir, Glaze Molly, Gombe Ben, Gumbe Anne, Hayes Peter, Itwi Sally, Juma Sheba, Kabarambi Anita, Kabengele Chishiba, Kafeero Paddy, Kakande Ayoub, Kanungi Jennifer, Kidega William, King Deborah, Mahira Rose, Malogo Roselyn, Matsoso Mabela, Michelo Clive, Moyo Annie, Mugaba Susan, Mugenya Irene, Muhumuza Patrick, Mujadidi Yama F, Muriuki Moses, Musale Vernon, Mutua Gaudensia, Muwowo Meya, Mwale Fatima, Mwangi Irene, Nakimbugwe Maria, Namuyanja Angella, Nduati Eunice, Nielsen Leslie, Nyange Jaquelyn, Oino Geofrey, Okech Brenda, Omosa-Manyonyi Gloria, Otieno Dan, Palmer Shaun, Phiri Hilda, Ramko Kelly, Rutishauser Rachel L, Sayeed Eddy, Sajabi Rose, Serwanga Jennifer, G-T Wee Edmund, Wenden Claire, Cicconi Paola, Fast Patricia, Gilmour Jill, Jaoko Walter, Kaleebu Pontiano, Kilembe William, Kuipers Hester, Sanders Eduard J, Hanke Tomáš
Center for Family Health Research Zambia (CFHRZ), Lusaka, Zambia.
Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
Lancet Microbe. 2025 Jun;6(6):101041. doi: 10.1016/j.lanmic.2024.101041. Epub 2025 May 16.
Even within the context of antiretroviral treatment and prevention, an HIV-1 vaccine remains the best strategy for ending the HIV/AIDS epidemic. A vaccine is particularly needed in sub-Saharan Africa, where HIV-1 greatly affects people's lives and economy. Here, we aimed to assess the safety and immunogenicity of candidate T-cell vaccines in African populations.
HIV-CORE 006 was a double-blind, randomised, placebo-controlled phase 1 trial conducted across four clinical research centres in Uganda, Kenya, and Zambia. Eligible participants were not pregnant, were living without HIV-1 or HIV-2, had a low likelihood of acquiring HIV-1, were aged 18-50 years, fully comprehended the purpose and details of this study as outlined in the participant information sheet, and passed an assessment of understanding before providing written informed consent. Participants were randomly assigned (9:2) to receive either a vaccine regimen or a placebo. The vaccine was administered as ChAdOx1.tHIVconsv1 (C1) followed by MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) in regimen C1-M3M4. The first primary outcome was the vaccines' safety assessment, assessed in all participants who received at least one vaccine or placebo dose. The second primary outcome evaluated the C1-M3M4 regimen's induction of HIVconsvX-specific T-cell responses by assessing the proportion of vaccine recipients who responded to the vaccination, assessed in all participants who received all doses of vaccine or placebo as per protocol. This study is registered with ClinicalTrials.gov, NCT04553016, and the Pan-African Clinical Trials Registry PACTR202006495409011, and is now closed.
Between July 15, 2021, and Nov 2, 2022, 89 healthy adults living without HIV-1 were randomly assigned, with 88 receiving either the vaccine (n=72) or placebo (n=16). Of these 88 participants, 57 (65%) were male and 31 (35%) were female. The C1, M3, and M4 vaccine components were well tolerated and induced HIVconsvX-specific responses in 70 (99%) of the 71 participants who completed all vaccine doses. Vaccine-elicited T cells peaked at a median of 2310 (IQR 1080-4480) IFN-γ spot-forming units per 10 peripheral blood mononuclear cells and recognised a median of eight (five to ten) of ten peptide pools spanning the HIVconsvX immunogen. The total frequencies of elicited T cells decreased 4·6 times over a 40-week follow-up period compared with the peak responses. Upon antigenic re-exposure, T cells proliferated, exhibited multiple effector functions, and inhibited HIV-1 representatives from clades A, B, C, and D.
Results from key sub-Saharan African populations supported the safety of the vaccine regimen previously shown in the first-in-human trial in the UK. The induction of T cells and their characteristics encourage vaccine integration into HIV-1 cure strategies, which could inform HIV-1 prevention efforts.
The European and Developing Countries Clinical Trials Partnership.
即使在抗逆转录病毒治疗和预防的背景下，HIV-1疫苗仍然是终结HIV/AIDS流行的最佳策略。撒哈拉以南非洲地区尤其需要一种疫苗，因为HIV-1对该地区人民的生活和经济造成了极大影响。在此，我们旨在评估候选T细胞疫苗在非洲人群中的安全性和免疫原性。
HIV-CORE 006是一项双盲、随机、安慰剂对照的1期试验，在乌干达、肯尼亚和赞比亚的四个临床研究中心开展。符合条件的参与者未怀孕，未感染HIV-1或HIV-2，感染HIV-1的可能性较低，年龄在18至50岁之间，完全理解参与者信息表中概述的本研究目的和细节，并在提供书面知情同意书之前通过理解评估。参与者被随机分配（9:2）接受疫苗方案或安慰剂。疫苗采用C1-M3M4方案给药，即先接种ChAdOx1.tHIVconsv1（C1），随后接种MVA.tHIVconsv3（M3）和MVA.tHIVconsv4（M4）。第一个主要结局是疫苗的安全性评估，在所有接受至少一剂疫苗或安慰剂的参与者中进行评估。第二个主要结局通过评估按方案接受所有剂量疫苗或安慰剂的所有参与者中对疫苗有反应的疫苗接受者比例，来评估C1-M3M4方案诱导HIVconsvX特异性T细胞反应的情况。本研究已在ClinicalTrials.gov（NCT04553016）和泛非临床试验注册中心（PACTR202006495409011）注册，现已结束。
在2021年7月15日至2022年11月2日期间，89名未感染HIV-1的健康成年人被随机分配，其中88人接受了疫苗（n = 72）或安慰剂（n = 16）。在这88名参与者中，57名（65%）为男性，31名（35%）为女性。C1、M3和M4疫苗成分耐受性良好，在完成所有疫苗剂量的71名参与者中的70名（99%）中诱导了HIVconsvX特异性反应。疫苗诱导的T细胞在每10个外周血单核细胞中产生的IFN-γ斑点形成单位中位数为2310（IQR 1080 - 4480），并识别了跨越HIVconsvX免疫原的10个肽池中的中位数为8个（5至1个）。与峰值反应相比，在40周的随访期内，诱导的T细胞总频率下降了4.6倍。再次接触抗原后，T细胞增殖，表现出多种效应功能，并抑制了A、B、C和D亚型的HIV-1代表株。
撒哈拉以南非洲关键人群的结果支持了先前在英国进行的首次人体试验中显示的疫苗方案的安全性。T细胞的诱导及其特性鼓励将疫苗纳入HIV-1治愈策略，这可能为HIV-1预防工作提供信息。
欧洲和发展中国家临床试验合作伙伴关系。
