Safety and immunogenicity of the RTS,S/AS01 malaria vaccine in infants and children identified as HIV-infected during a randomized trial in sub-Saharan Africa
Year: 2019
Type: article
Abstract: BACKGROUND: We assessed the safety and immunogenicity of the RTS,S/AS01 malaria vaccine in a subset of children identified as HIV-infected during a large phase III randomized controlled trial conducted in seven sub-Saharan African countries. METHODS: Infants 6-12 weeks and children 5-17 months old were randomized to receive 4 RTS,S/AS01 doses (R3R group), 3 RTS,S/AS01 doses plus 1 comparator vaccine dose (R3C group), or 4 comparator vaccine doses (C3C group) at study months 0, 1, 2 and 20. Infants and children with WHO stage III/IV HIV disease were excluded but HIV testing was not routinely performed on all participants; our analyses included children identified as HIV-infected based on medical history or clinical suspicion and confirmed by polymerase chain reaction or antibody testing. Serious adverse events (SAEs) and anti-circumsporozoite (CS) antibodies were assessed. RESULTS: Of 15459 children enrolled in the trial, at least 1953 were tested for HIV and 153 were confirmed as HIV-infected (R3R: 51; R3C: 54; C3C: 48). Among these children, SAEs were reported for 92.2% (95% CI: 81.1-97.8) in the R3R, 85.2% (72.9-93.4) in the R3C and 87.5% (74.8-95.3) in the C3C group over a median follow-up of 39.3, 39.4 and 38.3 months, respectively. Fifteen HIV-infected participants in each group (R3R: 29.4%, R3C: 27.8%, C3C: 31.3%) died during the study. No deaths were considered vaccination-related. In a matched case-control analysis, 1 month post dose 3 anti-CS geometric mean antibody concentrations were 193.3 EU/mL in RTS,S/AS01-vaccinated HIV-infected children and 491.5 EU/mL in RTS,S/AS01-vaccinated immunogenicity controls with unknown or negative HIV status (p = 0.0001). CONCLUSIONS: The safety profile of RTS,S/AS01 in HIV-infected children was comparable to that of the comparator (meningococcal or rabies) vaccines. RTS,S/AS01 was immunogenic in HIV-infected children but antibody concentrations were lower than in children with an unknown or negative HIV status. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT00866619.
Source: Vaccine
Authors: Lucas Otieno, Yolanda Guerra Mendoza, Samuel Adjei, Tsiri Agbenyega, Selidji Todagbe Agnandji, Pedro Aide, Pauline Akoo, Daniel Ansong, Kwaku Poku Asante, James A Berkley, Samwel Gesase, Mary J. Hamel, Irving Hoffman, Seyram Kaali, Portia Kamthunzi, Simon Kariuki, Peter Kremsner, Miguel Lanaspa, Bertrand Lell, Marc Lievens, John Lusingu, Anangisye Malabeja, Nahya Salim Masoud, Ali Takadir Mtoro, Patricia Njuguna, Opokua Ofori-Anyinam, Godfrey Allan Otieno, Walter Otieno, Seth Owusu-Agyei, Lode Schuerman, Hermann Sorgho, Marcel Tanner, Halidou Tinto, Innocent Valea, Pascale Vandoolaeghe, Jahit Sacarlal, Martina Oneko
Institutions: Kenya Medical Research Institute, GlaxoSmithKline (Belgium), Kwame Nkrumah University of Science and Technology, Centre de Recherche Médicales de Lambaréné, University of Tübingen, Manhiça Health Research Centre, Instituto Nacional de Saúde, Ministry of Health, KEMRI-Wellcome Trust Research Programme, Kintampo Health Research Centre, University of Oxford, National Institute for Medical Research, Centers for Disease Control and Prevention, Center for Global Health, Division of Parasitic Diseases and Malaria, University of North Carolina at Chapel Hill, Hospital Clínic de Barcelona, Barcelona Institute for Global Health, Universitat de Barcelona, Ifakara Health Institute, Muhimbili University of Health and Allied Sciences, Pwani University, Swiss Tropical and Public Health Institute, University of Basel, London School of Hygiene & Tropical Medicine, Institut de Recherche en Sciences de la Santé, Eduardo Mondlane University
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,450
OpenAlex ID: W2987234101