Safety and Broad Immunogenicity of HIVconsvX Conserved Mosaic Candidate T-Cell Vaccines Vectored by ChAdOx1 and MVA in HIV-CORE 006: A Double-Blind, Randomized, Placebo-Controlled Phase 1 Trial in Healthy Adults Living Without HIV-1 in Eastern and Southern Africa

• DOI: 10.2139/ssrn.4771407
• Publication Date: 2024-03-26T14:05:27Z
• Authors: Chama Chanda; Freddie Kibengo; Michael Mutua; Fred Ogada; Vincent Muturi-Kioi; Belkis M. Akis Y...; Mary Amondi; Andrea Baines; Vincent Basajja; Nicola Borthwick; Kefa Bosire; Elias Chambula; Paramesh Chetty; Kundai Chinyenze; Oscar Chirro; Alison Crook; Jan De Bont; Natalia Fernandez; Peter Ejou; Bashir Farah; Molly Glaze; Ben Gombe; Anne Gumbe; Peter Hayes; Sally Itwi; Sheba Juma; Anita Karambi; Chishiba Kabengele; Paddy Kafeero; Ayoub Kakande; Jennifer Kanungi; William Kidega; Deborah King; Hilda Phiri; Rose Mahira; Roselyn Malogo; Mabela Matsoso; Clive Michelo; Annie Moyo; Susan Mugaba; Irene Mugenya; Patrick Muhumuza; Yama Mujadidi; Moses Muriuki; Vernon Musale; Gaudensia Mutua; Meya Muwowo; Fatima Mwale; Irene Mwangi; Maria Nakimbugwe; Angella Namuyanja; Eunice Nduati; Leslie Nielsen; Jaquelyn Nyange; Geofrey Oino; Brenda Okech; Gloria Omosa; Dan Otieno; Shaun Palmer; Kelly Ramko; Rachel L. Rutish...; Eddy Sayeed; Rose Sajabi; Jennifer Serwanga; Edmund Wee; Claire Wenden; Paola Cicconi; Patricia Fast; Jill Gilmour; Walter Jaoko; Pontiano Kaleebu; William Kilembe; Hester Kuipers; Eduard Sanders; Tomas Hanke
• Keywords: Mosaic

Background: The world needs an effective HIV-1/AIDS vaccine. Even in the broader context of antiretroviral treatment and prevention, a vaccine remains best solution likely key component any package truly ending AIDS epidemic. Vaccine is particularly needed most affected regions like sub-Saharan Africa, where HIV-1 significantly impacts people's lives economy.Methods: CD8+ killer T cells impose selective pressure on their protective potential should be utilized for vaccination. Our program aims to develop T-cell vaccines has been informed by human data previous generations. current HIVconsvX immunogens are chimeric proteins six conserved Gag Pol sub-protein computed as bi-valent mosaics delivered simian adenovirus-derived ChAdOx1 poxvirus MVA. Here, we describe safety immunogenicity multisite phase 1 trial HIV-CORE 006 Eastern Southern Africa. Eighty-eight healthy males femalesreceived regimen or placebo (9:2). was administered ChAdOx1.tHIVconsv1 (C1) followed MVA.tHIVconsv3 (M3) MVA.tHIVconsv4 (M4) C1-M3M4. Findings: As per trial's primary endpoints, C1, M3 M4 components were well tolerated induced HIVconsvX-specific responses 70/71 (99%) recipients. secondary endpoints demonstrated that vaccine-elicited peaked at median (range) 2310 (270-14470) IFN-g spot-forming units/106 PBMC recognized 8 (0-10)/ten peptide pools spanning immunogen. total frequencies decreased 4·6-fold over 40-week follow-up. Upon antigenic re-exposure, proliferated, displayed multiple effector functions inhibited representative clades A, B, C D.Interpretation: Results populations confirm regimen's previously first-in-man UK. induction encourages further testing cure, which may, turn, guide prevention.Trial Registration: NCT04553016; PACTR202006495409011.Funding: funded European Developing Countries Clinical Trials Partnership award SRIA2015-1066 Globally Relevant Europe-Africa Trial (GREAT) consortium (www.jenner.ac.uk/research/infectious-diseases/hiv-vaccine-programme/great-partnership). GMP manufacture (SRIA2015-1066) (C1 M4) International Initiative (IAVI) through support United States Agency Development other donors (M3). full list IAVI available http://www.iavi.org. contents this manuscript responsibility authors do not necessarily reflect views USAID US Government. analyses part supported with investment ID INV-046661 from Melinda & Bill Gates Foundation R.L.R. University California San Francisco research subaward agreement no. 14122sc T.H. UOXF.Declaration Interest: have no conflict interest except T.H., who co-inventor protected under EP14846993.5 PCT/US14/58422 (WO2015048785).Ethical Approval: Approvals granted follows: MRC/UVRI London School Hygiene Tropical Medicine Uganda Research Unit, Masaka (MUL): approved Virus Institute REC (GC/127/20/06/761), National Council Science Technology (HS844ES), Drug Authority (CTC 0171/2021); Kenya Medical Institute-Wellcome Trust Programme Kilifi (KWTRP): Committee (CSC 180), KEMRI Scientific Ethics Review Unit (SERU 4025), Commission Science, Innovation (NACOSTI/P/23/23155/) Pharmacy Poisons Board (PPB/ECCT/20/10/01/2021); KAVI-Institute (KAVI-ICR), Nairobi, Nairobi Kenyatta Hospital (P863/10/2019), NACOSTI (NACOSTI/286477) PPB (PPB/ECCT/20/06/09/2020); Center Family Health Zambia, formerly ZEHRP, Lusaka (CFHRZ): Zambia Biomedical (UNZABREC 495-2019) Medicines Regulatory (CT 098), Biosafety (NBA/101/16/1), Authority; Oxford (OXTREC 56-19). study conducted according principles Declaration Helsinki (2008) complied Conference Harmonization Good Practice guidelines Participatory Practices.