Children with hemoglobin C or S trait have low serologic responses to a subset of malaria variant surface antigens

Rachel D Bailey; Jonathan G Lawton; Amadou Niangaly; Emily M Stucke; Jason A Bailey; Andrea A Berry; Amed Ouattara; Drissa Coulibaly; Kirsten E Lyke; Matthew B Laurens; Albert E Zhou; Jozelyn Pablo; Algis Jasinskas; Rie Nakajima; Matthew Adams; Shannon Takala-Harrison; Bourema Kouriba; Abdoulaye K Kone; Aldiouma Guindo; J Alexandra Rowe; Dapa A Diallo; Ogobara K Doumbo; Philip L Felgner; Christopher V Plowe; Mahamadou A Thera; Mark A Travassos

doi:10.1016/j.jinf.2024.106257

Children with hemoglobin C or S trait have low serologic responses to a subset of malaria variant surface antigens

J Infect. 2024 Oct;89(4):106257. doi: 10.1016/j.jinf.2024.106257. Epub 2024 Aug 30.

Authors

Rachel D Bailey¹, Jonathan G Lawton², Amadou Niangaly³, Emily M Stucke⁴, Jason A Bailey⁵, Andrea A Berry⁶, Amed Ouattara⁷, Drissa Coulibaly⁸, Kirsten E Lyke⁹, Matthew B Laurens¹⁰, Albert E Zhou¹¹, Jozelyn Pablo¹², Algis Jasinskas¹³, Rie Nakajima¹⁴, Matthew Adams¹⁵, Shannon Takala-Harrison¹⁶, Bourema Kouriba¹⁷, Abdoulaye K Kone¹⁸, Aldiouma Guindo¹⁹, J Alexandra Rowe²⁰, Dapa A Diallo²¹, Ogobara K Doumbo²², Philip L Felgner²³, Christopher V Plowe²⁴, Mahamadou A Thera²⁵, Mark A Travassos²⁶

Affiliations

¹ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
² Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
³ Malaria Research and Training Center, University Science, Techniques and Technologies of Bamako, BP 1805, Point G, Bamako, Mali. Electronic address: [email protected].
⁴ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
⁵ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
⁶ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
⁷ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
⁸ Malaria Research and Training Center, University Science, Techniques and Technologies of Bamako, BP 1805, Point G, Bamako, Mali. Electronic address: [email protected].
⁹ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
¹⁰ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
¹¹ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
¹² Division of Infectious Diseases, Department of Medicine, University of California, 101 The City Drive, Orange, CA 92868, United States of America. Electronic address: [email protected].
¹³ Division of Infectious Diseases, Department of Medicine, University of California, 101 The City Drive, Orange, CA 92868, United States of America. Electronic address: [email protected].
¹⁴ Division of Infectious Diseases, Department of Medicine, University of California, 101 The City Drive, Orange, CA 92868, United States of America. Electronic address: [email protected].
¹⁵ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
¹⁶ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
¹⁷ Malaria Research and Training Center, University Science, Techniques and Technologies of Bamako, BP 1805, Point G, Bamako, Mali. Electronic address: [email protected].
¹⁸ Malaria Research and Training Center, University Science, Techniques and Technologies of Bamako, BP 1805, Point G, Bamako, Mali. Electronic address: [email protected].
¹⁹ Malaria Research and Training Center, University Science, Techniques and Technologies of Bamako, BP 1805, Point G, Bamako, Mali. Electronic address: [email protected].
²⁰ Center for Immunity, Infection and Evolution, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Charlotte Auerbach Road, Edinburgh EH9 3FL, United Kingdom. Electronic address: [email protected].
²¹ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
²² Malaria Research and Training Center, University Science, Techniques and Technologies of Bamako, BP 1805, Point G, Bamako, Mali. Electronic address: [email protected].
²³ Division of Infectious Diseases, Department of Medicine, University of California, 101 The City Drive, Orange, CA 92868, United States of America. Electronic address: [email protected].
²⁴ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].
²⁵ Malaria Research and Training Center, University Science, Techniques and Technologies of Bamako, BP 1805, Point G, Bamako, Mali. Electronic address: [email protected].
²⁶ Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W. Baltimore St., HSF1 Room 480, Baltimore, MD 21201, United States of America. Electronic address: [email protected].

PMID: 39216830
DOI: 10.1016/j.jinf.2024.106257

Abstract

Children with hemoglobin AC or AS have decreased susceptibility to clinical malaria. Parasite variant surface antigen (VSA) presentation on the surface of infected erythrocytes is altered in erythrocytes with hemoglobin C (Hb AC) or sickle trait (Hb AS) mutations in vitro. The protective role of incomplete or altered VSA presentation against clinical malaria in individuals with Hb AC or AS is unclear. Using a high-throughput protein microarray, we sought to use serological responses to VSAs as a measure of host exposure to VSAs among Malian children with Hb AC, Hb AS, or wildtype hemoglobin (Hb AA). In uncomplicated malaria, when compared to Hb AA children, Hb AC children had significantly lower serological responses to extracellular Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) domains but did not differ in responses to intracellular PfEMP1 domains and other VSAs, including members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family. Healthy children with Hb AC and Hb AS genotypes recognized fewer extracellular PfEMP1s compared to children with Hb AA, especially CD36-binding PfEMP1s. These reduced serologic responses may reflect reduced VSA presentation or lower parasite exposure in children with Hb AC or AS and provide insights into mechanisms of protection.

Keywords: Hemoglobin C; Hemoglobin S; Malaria; Mali; Plasmodium falciparum; Protein microarray.

MeSH terms

Adolescent
Antibodies, Protozoan / blood
Antibodies, Protozoan / immunology
Antigens, Protozoan* / genetics
Antigens, Protozoan* / immunology
Antigens, Surface / genetics
Antigens, Surface / immunology
Child
Child, Preschool
Female
Hemoglobin C* / genetics
Hemoglobin, Sickle / genetics
Humans
Infant
Malaria, Falciparum* / blood
Malaria, Falciparum* / immunology
Male
Mali / epidemiology
Plasmodium falciparum* / genetics
Plasmodium falciparum* / immunology
Protein Array Analysis
Protozoan Proteins* / genetics
Protozoan Proteins* / immunology
Sickle Cell Trait* / blood
Sickle Cell Trait* / genetics
Sickle Cell Trait* / immunology

Substances

Antigens, Protozoan
Protozoan Proteins
Hemoglobin C
erythrocyte membrane protein 1, Plasmodium falciparum
Antibodies, Protozoan
Hemoglobin, Sickle
Antigens, Surface