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Vaccine. 2020 Jan 22;38(4):897-906. doi: 10.1016/j.vaccine.2019.10.077. Epub 2019 Nov 7.

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.

Author information

1
KEMRI-Walter Reed Project, Kombewa, Kenya. Electronic address: Lucas.Tina@usamru-k.org.
2
GSK, Wavre, Belgium. Electronic address: Yolanda.x.guerra@gsk.com.
3
Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Electronic address: kwakusam@yahoo.com.
4
Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Electronic address: tsiri@ghana.com.
5
Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon and Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany. Electronic address: agnandjis@lambarene.org.
6
Centro de Investigação em Saúde de Manhiça, Manhiça, Mozambique; National Institute of Health, Ministry of Health, Maputo, Mozambique. Electronic address: pedro.aide@manhica.net.
7
Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Kilifi, Kenya. Electronic address: byancamy@gmail.com.
8
Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Electronic address: ansongd@yahoo.com.
9
Kintampo Health Research Center, Kintampo, Ghana. Electronic address: kwakupoku.asante@kintampo-hrc.org.
10
Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Kilifi, Kenya; Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. Electronic address: JBerkley@kemri-wellcome.org.
11
National Institute for Medical Research, Korogwe, Tanzania. Electronic address: sgesase@yahoo.com.
12
Malaria Branch Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: hamelm@who.int.
13
Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. Electronic address: hoffmani@med.unc.edu.
14
Kintampo Health Research Center, Kintampo, Ghana. Electronic address: kaali.seyram@kintampo-hrc.org.
15
Department of Medicine, University of North Carolina, Chapel Hill, NC, USA. Electronic address: pkamthunzi@unclilongwe.org.
16
Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya. Electronic address: SKariuki@kemricdc.org.
17
Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon and Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany. Electronic address: peter.kremsner@uni-tuebingen.de.
18
Centro de Investigação em Saúde de Manhiça, Manhiça, Mozambique; Barcelona Institute for Global Health (ISGlobal), Hospital Clínic-Universitat de Barcelona, Spain. Electronic address: mlanaspa@sjdhospitalbarcelona.org.
19
Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon and Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany. Electronic address: bertrand.lell@lambarene.org.
20
GSK, Wavre, Belgium. Electronic address: marc.lievens@gsk.com.
21
National Institute for Medical Research, Korogwe, Tanzania. Electronic address: jpalusingu@yahoo.co.uk.
22
National Institute for Medical Research, Korogwe, Tanzania. Electronic address: malabeja1@yahoo.com.
23
Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania; Ifakara Health Institute, Bagamoyo, Tanzania. Electronic address: nsalim@ihi.or.tz.
24
Ifakara Health Institute, Bagamoyo, Tanzania. Electronic address: amtoro@ihi.or.tz.
25
Kenya Medical Research Institute-Wellcome Trust Research Programme, Centre for Geographic Medicine Research, Kilifi, Kenya; Pwani University, Kilifi, Kenya. Electronic address: njugunap@who.int.
26
GSK, Wavre, Belgium. Electronic address: opokua.ofori-anyinam@gsk.com.
27
KEMRI-Walter Reed Project, Kombewa, Kenya. Electronic address: Allan.Otieno@usamru-k.org.
28
KEMRI-Walter Reed Project, Kombewa, Kenya. Electronic address: Walter.otieno@usamru-k.org.
29
Kintampo Health Research Center, Kintampo, Ghana; Diseases Control Department, London School of Hygiene and Tropical Medicine, London, UK. Electronic address: seth.owusu-agyei@kintampo-hrc.org.
30
GSK, Wavre, Belgium. Electronic address: lode.schuerman@gsk.com.
31
Institut de Recherche en Sciences de la Santé, Nanoro, Burkina Faso. Electronic address: hsorgho@hotmail.com.
32
Muhimbili University of Health and Allied Sciences (MUHAS), Dar es Salaam, Tanzania; Ifakara Health Institute, Bagamoyo, Tanzania; Swiss Tropical and Public Health Institute, Basel, Switzerland and University of Basel, Basel, Switzerland. Electronic address: marcel.tanner@unibas.ch.
33
Institut de Recherche en Sciences de la Santé, Nanoro, Burkina Faso. Electronic address: halidoutinto@gmail.com.
34
Institut de Recherche en Sciences de la Santé, Nanoro, Burkina Faso. Electronic address: innocentvalea@yahoo.fr.
35
GSK, Wavre, Belgium. Electronic address: pascale.vandoolaeghe@gsk.com.
36
Centro de Investigação em Saúde de Manhiça, Manhiça, Mozambique; Faculdade de Medicina, Universidade Eduardo Mondlane (UEM), Maputo, Mozambique. Electronic address: jahityash2002@gmail.com.
37
Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya. Electronic address: tinaoneko@gmail.com.

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.

KEYWORDS:

Children; HIV; Immunogenicity; Malaria; RTS; S/AS01 vaccine; Safety

PMID:
31708182
DOI:
10.1016/j.vaccine.2019.10.077
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