Immune correlates of protection against clinical malaria are difficult to ascertain in low-transmission areas because of the limited number of malaria cases. We collected blood samples from 5,753 individuals in a Kenyan highland area, ascertained malaria incidence in this population over the next 6 years, and then compared antibody responses to 11 Plasmodium falciparum vaccine candidate antigens in individuals who did versus did not develop clinical malaria in a nested case-control study (154 cases and 462 controls). Individuals were matched by age and village. Antigens tested included circumsporozoite protein (CSP), liver-stage antigen (LSA)-1, apical membrane antigen-1 FVO and 3D7 strains, erythrocyte-binding antigen-175, erythrocyte-binding protein-2, merozoite surface protein (MSP)-1 FVO and 3D7 strains, MSP-3, and glutamate-rich protein (GLURP) N-terminal non-repetitive (R0) and C-terminal repetitive (R2) regions. After adjustment for potential confounding factors, the presence of antibodies to LSA-1, GLURP-R2, or GLURP-R0 was associated with decreased odds of developing clinical malaria (odds ratio [OR], [95% CI] 0.56 [0.36-0.89], 0.56 [0.36-0.87], and 0.77 [0.43-1.02], respectively). Levels of antibodies to LSA-1, GLURP-R2, and CSPwere associated with decreased odds of developing clinical malaria (OR [95% CI]; 0.61 [0.41-0.89], 0.60 [0.43-0.84], and 0.49 [0.24-0.99], for every 10-fold increase in antibody levels, respectively). The presence of antibodies to CSP, GLURP-R0, GLURP-R2, and LSA-1 combined best-predicted protection from clinical malaria. Antibodies to CSP, GLURP-R0, GLURP-R2, and LSA-1 are associated with protection against clinical malaria in a low-transmission setting. Vaccines containing these antigens should be evaluated in low malaria transmission areas.
Bibliographical noteFunding Information:
Financial support: This project was supported by grants from NIH-NIAID (NCT00393757), NIH Fogarty International Center (D43 TW0080085), and the University of Minnesota Amplatz Children’s Hospital, and an NIH research training grant (R25 TW009345) awarded to the Northern Pacific Global Health Fellows Program by Fogarty International Center in partnership with several NIH institutes (NIMH, NIGMS, NHLBI, OAR, and OWH).
© 2019 by The American Society of Tropical Medicine and Hygiene.
- Antibodies, Protozoan/immunology
- Antibody Formation
- Antigens, Protozoan/immunology
- Case-Control Studies
- Child, Preschool
- Malaria, Falciparum/epidemiology
- Middle Aged
- Plasmodium falciparum/immunology
- Protozoan Proteins/immunology
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural