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

BMC Medicine

Augusto J. Nhabomba¹  Chenjerai Jairoce¹  Clarissa Valim²  Rebeca Santano³  Itziar Ubillos³  Joseph J. Campo³  Gemma Moncunill³  Ruth Aguilar³  Núria Díez-Padrisa³  Aintzane Ayestaran³  Marta Vidal³  Carlota Dobaño³  Nana Aba Williams³  Alfons Jiménez³  Ross L. Coppel⁴  David Cavanagh⁵  Seth Owusu-Agyei⁶  Kwaku Poku Asante⁶  David Dosoo⁶  James G. Beeson⁷  Virander Chauhan⁸  Deepak Gaur⁸  Chetan Chitnis⁸  David Lanar⁹  Evelina Angov⁹  Sheetij Dutta⁹  Ben Gyan^1,10  Benoit Gamain^1,11 

[1] Centro de Investigação em Saúde de Manhiça (CISM);Department of Osteopathic Medical Specialties, Michigan State University;ISGlobal, Hospital Clínic - Universitat de Barcelona, Carrer Rosselló 153;Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University;Institute of Immunology & Infection Research and Centre for Immunity, Infection & Evolution, Ashworth Laboratories, School of Biological Sciences, University of Edinburgh;Kintampo Health Research Centre;Macfarlane Burnet Institute for Medical Research and Public Health;Malaria Group, International Centre for Genetic Engineering and Biotechnology (ICGEB);Malaria Vaccine Branch, Walter Reed Army Institute of Research;Noguchi Memorial Institute for Medical Research, University of Ghana;Université Sorbonne Paris Cité, Université Paris Diderot, Inserm, INTS, Unité Biologie Intégrée du Globule Rouge UMR_S1134, Laboratoire d’Excellence GR-Ex;

关键词: Malaria;    Plasmodium falciparum;    Vaccine;    RTS,S;    Antibody;    Pre-erythrocytic antigens;   

DOI  :  10.1186/s12916-019-1378-6

来源: DOAJ

【 摘 要 】

Abstract 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 (MSP142, AMA1) and levels correlated with risk of clinical malaria over 1-year follow-up. In addition, we show for the first time that RTS,S vaccination increased IgG levels to a specific group of pre-erythrocytic and blood-stage antigens (MSP5, MSP1 block 2, RH4.2, EBA140, and SSP2/TRAP) which levels correlated with protection against clinical malaria (odds ratio [95% confidence interval] 0.53 [0.3–0.93], p = 0.03, for MSP1; 0.52 [0.26–0.98], p = 0.05, for SSP2) in multivariable logistic regression analyses. 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.

【 授权许可】

Unknown