Antibodies to Peptides in Semiconserved Domains of RIFINs and STEVORs Correlate with Malaria Exposure
Albert E. Zhou,
Andrea A. Berry,
Jason A. Bailey,
Andrew Pike,
Antoine Dara,
Sonia Agrawal,
Emily M. Stucke,
Amed Ouattara,
Drissa Coulibaly,
Kirsten E. Lyke,
Matthew B. Laurens,
Matthew Adams,
Shannon Takala-Harrison,
Jozelyn Pablo,
Algis Jasinskas,
Rie Nakajima,
Amadou Niangaly,
Bourema Kouriba,
Abdoulaye K. Kone,
J. Alexandra Rowe,
Ogobara K. Doumbo,
Mahamadou A. Thera,
Jigar J. Patel,
John C. Tan,
Philip L. Felgner,
Christopher V. Plowe,
Mark A. Travassos
Affiliations
Albert E. Zhou
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Andrea A. Berry
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Jason A. Bailey
The EMMES Corporation, Rockville, Maryland, USA
Andrew Pike
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Antoine Dara
Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali
Sonia Agrawal
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Emily M. Stucke
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Amed Ouattara
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Drissa Coulibaly
Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali
Kirsten E. Lyke
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Matthew B. Laurens
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Matthew Adams
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Shannon Takala-Harrison
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
Jozelyn Pablo
Division of Infectious Diseases, Department of Medicine, University of California, Irvine, Irvine, California, USA
Algis Jasinskas
Division of Infectious Diseases, Department of Medicine, University of California, Irvine, Irvine, California, USA
Rie Nakajima
Division of Infectious Diseases, Department of Medicine, University of California, Irvine, Irvine, California, USA
Amadou Niangaly
Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali
Bourema Kouriba
Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali
Abdoulaye K. Kone
Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali
J. Alexandra Rowe
Centre for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom
Ogobara K. Doumbo
Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali
Mahamadou A. Thera
Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali
Jigar J. Patel
Roche NimbleGen, Inc., Madison, Wisconsin, USA
John C. Tan
Roche NimbleGen, Inc., Madison, Wisconsin, USA
Philip L. Felgner
Division of Infectious Diseases, Department of Medicine, University of California, Irvine, Irvine, California, USA
Christopher V. Plowe
Duke Global Health Institute, Duke University, Durham, North Carolina, USA
Mark A. Travassos
Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA
ABSTRACT The repetitive interspersed family (RIFIN) and the subtelomeric variable open reading frame (STEVOR) family represent two of three major Plasmodium falciparum variant surface antigen families involved in malaria pathogenesis and immune evasion and are potential targets in the development of natural immunity. Protein and peptide microarrays populated with RIFINs and STEVORs associated with severe malaria vulnerability in Malian children were probed with adult and pediatric sera to identify epitopes that reflect malaria exposure. Adult sera recognized and reacted with greater intensity to all STEVOR proteins than pediatric sera did. Serorecognition of and seroreactivity to peptides within the semiconserved domain of STEVORs increased with age and seasonal malaria exposure, while serorecognition and seroreactivity increased for the semiconserved and second hypervariable domains of RIFINs only with age. Serologic responses to RIFIN and STEVOR peptides within the semiconserved domains may play a role in natural immunity to severe malaria. IMPORTANCE 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.
