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Review
. 2020 Dec;103(6):2174-2182.
doi: 10.4269/ajtmh.18-0805. Epub 2020 Oct 27.

Antibody Correlates of Protection from Clinical Plasmodium falciparum Malaria in an Area of Low and Unstable Malaria Transmission

Karen E S Hamre  1   2   3 , Bartholomew N Ondigo  4   5   6 , James S Hodges  7 , Sheetij Dutta  8 , Michael Theisen  9 , George Ayodo  5   10 , Chandy C John  1   2   4   11
Affiliations
Review

Antibody Correlates of Protection from Clinical Plasmodium falciparum Malaria in an Area of Low and Unstable Malaria Transmission

Karen E S Hamre et al. Am J Trop Med Hyg. 2020 Dec.

Abstract

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 CSP were 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.

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Figures

Figure 1.
Figure 1.
Clinical malaria incidence per 1,000 persons in Kipsamoite and Kapsisiywa, Kenya, June 2007–June 2013.
Figure 2.
Figure 2.
Clinical malaria incidence per 1,000 persons in Kipsamoite and Kapsisiywa, Kenya, June 2007–June 2013, by age group.
Figure 3.
Figure 3.
Area under the receiver operating characteristic curve; 0.6664 for the combination of circumsporozoite protein, glutamate-rich protein N-terminal non-repetitive region, glutamate-rich protein C-terminal repetitive region, and liver-stage antigen-1 as continuous measures; n = 616 (154 cases and 462 controls).
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