Antibodies to Peptides in Semiconserved Domains of RIFINs and STEVORs Correlate with Malaria Exposure

Author:

Zhou Albert E.1,Berry Andrea A.1,Bailey Jason A.2,Pike Andrew1,Dara Antoine3,Agrawal Sonia1,Stucke Emily M.1,Ouattara Amed1,Coulibaly Drissa3,Lyke Kirsten E.1,Laurens Matthew B.1ORCID,Adams Matthew1,Takala-Harrison Shannon1,Pablo Jozelyn4,Jasinskas Algis4,Nakajima Rie4,Niangaly Amadou3,Kouriba Bourema3,Kone Abdoulaye K.3,Rowe J. Alexandra5,Doumbo Ogobara K.3,Thera Mahamadou A.3,Patel Jigar J.6,Tan John C.6,Felgner Philip L.4,Plowe Christopher V.7,Travassos Mark A.1ORCID

Affiliation:

1. Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA

2. The EMMES Corporation, Rockville, Maryland, USA

3. Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali

4. Division of Infectious Diseases, Department of Medicine, University of California, Irvine, Irvine, California, USA

5. Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom

6. Roche NimbleGen, Inc., Madison, Wisconsin, USA

7. Duke Global Health Institute, Duke University, Durham, North Carolina, USA

Abstract

Malaria, an infectious disease caused by the parasite Plasmodium falciparum , causes nearly 435,000 deaths annually worldwide. RIFINs and STEVORs are two variant surface antigen families that are involved in malaria pathogenesis and immune evasion. Recent work has shown that a lack of humoral immunity to these proteins is associated with severe malaria vulnerability in Malian children. This is the first study to have compared serologic responses of children and adults to RIFINs and STEVORs in settings of malaria endemicity and to examine such serologic responses before and after a clinical malaria episode. Using microarrays, we determined that the semiconserved domains in these two parasite variant surface antigen families harbor peptides whose seroreactivity reflects malaria exposure. A similar approach has the potential to illuminate the role of variant surface antigens in the development of natural immunity to clinical malaria. Potential vaccines for severe malaria should include consideration of peptides within the semiconserved domains of RIFINs and STEVORs.

Funder

Meyerhoff Foundation

University of Maryland, Baltimore Medical Scientist Training Program

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | Fogarty International Center

Howard Hughes Medical Institute

Burroughs Wellcome Fund

Doris Duke Charitable Foundation

HHS | NIH | National Heart, Lung, and Blood Institute

Passano Foundation

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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