RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study.
Antibody
Blood-stage antigens
Malaria
Maternal antibodies
Naturally acquired immunity
Plasmodium falciparum
Pre-erythrocytic antigens
Protection
RTS,S
Vaccine
Journal
BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723
Informations de publication
Date de publication:
14 08 2019
14 08 2019
Historique:
received:
20
02
2019
accepted:
27
06
2019
entrez:
15
8
2019
pubmed:
15
8
2019
medline:
7
1
2020
Statut:
epublish
Résumé
Vaccination and naturally acquired immunity against microbial pathogens may have complex interactions that influence disease outcomes. To date, only vaccine-specific immune responses have routinely been investigated in malaria vaccine trials conducted in endemic areas. We hypothesized that RTS,S/A01E immunization affects acquisition of antibodies to Plasmodium falciparum antigens not included in the vaccine and that such responses have an impact on overall malaria protective immunity. We evaluated IgM and IgG responses to 38 P. falciparum proteins putatively involved in naturally acquired immunity to malaria in 195 young children participating in a case-control study nested within the African phase 3 clinical trial of RTS,S/AS01E (MAL055 NCT00866619) in two sites of different transmission intensity (Kintampo high and Manhiça moderate/low). We measured antibody levels by quantitative suspension array technology and applied regression models, multimarker analysis, and machine learning techniques to analyze factors affecting their levels and correlates of protection. RTS,S/AS01E immunization decreased antibody responses to parasite antigens considered as markers of exposure (MSP1 Increased antibody responses to specific P. falciparum antigens in subjects immunized with this partially efficacious vaccine upon natural infection may contribute to overall protective immunity against malaria. Inclusion of such antigens in multivalent constructs could result in more efficacious second-generation multistage vaccines.
Sections du résumé
BACKGROUND
Vaccination and naturally acquired immunity against microbial pathogens may have complex interactions that influence disease outcomes. To date, only vaccine-specific immune responses have routinely been investigated in malaria vaccine trials conducted in endemic areas. We hypothesized that RTS,S/A01E immunization affects acquisition of antibodies to Plasmodium falciparum antigens not included in the vaccine and that such responses have an impact on overall malaria protective immunity.
METHODS
We evaluated IgM and IgG responses to 38 P. falciparum proteins putatively involved in naturally acquired immunity to malaria in 195 young children participating in a case-control study nested within the African phase 3 clinical trial of RTS,S/AS01E (MAL055 NCT00866619) in two sites of different transmission intensity (Kintampo high and Manhiça moderate/low). We measured antibody levels by quantitative suspension array technology and applied regression models, multimarker analysis, and machine learning techniques to analyze factors affecting their levels and correlates of protection.
RESULTS
RTS,S/AS01E immunization decreased antibody responses to parasite antigens considered as markers of exposure (MSP1
CONCLUSIONS
Increased antibody responses to specific P. falciparum antigens in subjects immunized with this partially efficacious vaccine upon natural infection may contribute to overall protective immunity against malaria. Inclusion of such antigens in multivalent constructs could result in more efficacious second-generation multistage vaccines.
Identifiants
pubmed: 31409398
doi: 10.1186/s12916-019-1378-6
pii: 10.1186/s12916-019-1378-6
pmc: PMC6693200
doi:
Substances chimiques
Antibodies, Protozoan
0
Antigens, Protozoan
0
Malaria Vaccines
0
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
157Subventions
Organisme : NIAID NIH HHS
ID : R01 AI095789
Pays : United States
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