Pattern and association of immunoglobulin G antibodies to AMA1, GLURP, and MSP3 with protection from malaria in a cohort of Cameroonian children living in Mutengene: Anaemia a possible collateral damage?

Abstract

Understanding the characteristics of naturally acquired immunity in different epidemiologic settings is essential for vaccine development and testing. The relationship between antibodies against four malaria vaccine candidate antigens and protection from malaria in a cohort of Cameroonian children was assessed. Immunoglobulin (Ig)G and IgG subclasses against recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1), glutamate rich protein (GLURP) R0, GLURP R2 and merozoite surface protein 3 (MSP3) in the plasma of 357 Cameroonian children were measured by sandwich ELISA at three time points (baseline, 6 months and 12 months) during which time participants were monitored for malaria.Total IgG to all four antigens correlated positively with age (0.51 ≤ r ≤ 0.23, p < 0.001) at all three time points. Adjusting for age, total IgG, IgG1, IgG3, IgG2 (except for MSP3 IgG2) antibody levels to all four antigens were associated with protection against malaria parasitaemia at baseline. GLURP R0 IgG (F = 35.7, p < 0.001), GLURP R2 IgG (F = 16.5, p < 0.001), AMA1–3D7 IgG2 (F = 10.8, p < 0.001) and AMA1-3D7 IgG3 (F = 4.01, p = 0.019) decreased with a corresponding decrease in malaria cases (χ = 10.4, p = 0.034) across the three time points, contrary to the increase observed in MSP3 IgG (F = 8.9, p < 0.001) and MSP3 IgG2 (F = 44.2, p < 0.001). Increased levels of AMA1–3D7 IgG [OR = 4.13, 95% CI (1.09 – 15.65), p = 0.037] and MSP3 IgG1 [OR = 8.16, 95% CI (1.06 – 62.64), p = 0.044] were associated with susceptibility to anaemia after controlling for age and parasitaemia.Total IgG, cytophilic subclasses and IgG2 to all the antigens (except MSP3 IgG2) were associated with malaria protection while MSP3 IgG seemed to persist longer. The relationship between malaria specific antibodies and anaemia warrants further studies.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was jointly funded by the European and Developing Countries Clinical Trials Partnership (EDCTP) through a Central African Network for Tuberculosis, HIV/AIDS and Malaria (CANTAM) grant awarded to Professor Achidi Eric (EAA) and from an OWSD (Organization for Women in Science for the Developing World) Postgraduate sandwich fellowship awarded to Njua Clarisse Yafi (CN-Y). Research support was also provided in the form of research allowances from Ministry of Higher Education in Cameroon through the Faculty of Science of the University of Yaounde I.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethical clearance for this study was obtained from the National Ethics Committee in Cameroon (No198/CNE/SE/2010). Administrative authorisation was obtained from the Ministry of Public Health and the South West Regional Delegation of Public Health. Written informed consent was obtained from the parents or guardians of the children along with the signature of a witness before the children were enrolled into the study. Samples were only collected by trained medical personnel using sterile and pain-reducing equipment.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors

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