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

Carlota Dobanõ, Itziar Ubillos, Chenjerai Jairoce, Ben Gyan, Marta Vidal, Alfons Jiménez, Rebeca Santano, David Dosoo, Augusto J. Nhabomba, Aintzane Ayestaran, Ruth Aguilar, Nana Aba Williams, Núria Diéz-Padrisa, David Lanar, Virander Chauhan, Chetan Chitnis, Sheetij Dutta, Deepak Gaur, Evelina Angov, Kwaku Poku AsanteSeth Owusu-Agyei, Clarissa Valim, Benoit Gamain, Ross L. Coppel, David Cavanagh, James G. Beeson, Joseph J. Campo, Gemma Moncunill

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26 Citations (Scopus)

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 Manhica 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.

Original languageEnglish
Article number157
Number of pages19
JournalBMC Medicine
Volume17
Issue number1
DOIs
Publication statusPublished - 14 Aug 2019

Keywords

  • Antibody
  • Blood-stage antigens
  • Malaria
  • Maternal antibodies
  • Naturally acquired immunity
  • Plasmodium falciparum
  • Pre-erythrocytic antigens
  • Protection
  • RTS,S
  • Vaccine

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