Antibody Correlates of Risk of Clinical Malaria in an Area of Low and Unstable Malaria Transmission in Western Kenya

Overview

Journal Malar J

Publisher Biomed Central

Specialty Tropical Medicine

Date 2025 Mar 3

PMID 40033373

Authors

Eliud O Odhiambo

Kagan A Mellencamp

Bartholomew N Ondigo

Karen E S Hamre

James G Beeson

D Herbert Opi

David L Narum

George Ayodo

Chandy C John

Affiliations

Soon will be listed here.

Abstract

Background: Defining antibody correlates of protection against clinical malaria in areas of low and unstable transmission is challenging because of limited malaria cases in these areas. Additionally, clinical malaria affects both adults and children in areas of low and unstable transmission, but it is unclear whether antibody correlates of protection against malaria differ with age.

Methods: Blood samples were obtained from 5753 individuals in Kenyan highland area with low and seasonal malaria transmission in 2007 and recorded episodes of clinical malaria in this population from 2007 to 2017. Using a nested case-control study design, participants who developed clinical malaria (cases) were matched by age and village to those who did not (controls). Immunoglobulin (Ig)G, IgG1, IgG3, IgA and IgM responses to 16 Plasmodium falciparum antigens were compared in individuals < 5 years old (80 cases vs. 240 controls), 5-14 years old (103 cases vs. 309 controls) and ≥ 15 years old (118 cases vs. 354 controls). Antibody level was correlated with risk of clinical malaria, adjusted for malaria exposure markers.

Results: In all age groups, most antibodies were not associated with risk of clinical malaria. In children < 5 years, higher levels of IgG to GLURP-R2 and MSP-2, IgG1 to GLURP-R2, and IgG3 to MSP-2 were associated with reduced risk of clinical malaria, while higher IgG3 levels to CSP were associated with increased risk of clinical malaria. In children 5-14 years and individuals ≥ 15 years, higher antibody levels to multiple P. falciparum antigens were associated with an increased risk of clinical malaria, and none were associated with decreased risk of clinical malaria.

Conclusions: Antibody correlates of protection against clinical malaria were observed only in children < 5 years old in this area of low and unstable malaria transmission. In older children and adults in this area, some antibody responses correlated with increased risk of clinical malaria. Future studies in low malaria transmission areas should evaluate the comparative contributions of cellular and humoral immunity to protection from clinical malaria in young children versus older children and adults.

References

Odhiambo E, Datta D, Guyah B, Ayodo G, Ondigo B, Abongo B . HIV infection drives IgM and IgG3 subclass bias in Plasmodium falciparum-specific and total immunoglobulin concentration in Western Kenya. Malar J. 2019; 18(1):297. PMC: 6716850. DOI: 10.1186/s12936-019-2915-7. View

Mensah-Brown H, Aspeling-Jones H, Delimini R, Asante K, Amlabu E, Bah S . Antibody Reactivity to Merozoite Antigens in Ghanaian Adults Correlates With Growth Inhibitory Activity Against in Culture. Open Forum Infect Dis. 2019; 6(7):ofz254. PMC: 6611546. DOI: 10.1093/ofid/ofz254. View

Boyle M, Chan J, Handayuni I, Reiling L, Feng G, Hilton A . IgM in human immunity to malaria. Sci Adv. 2019; 5(9):eaax4489. PMC: 6760923. DOI: 10.1126/sciadv.aax4489. View

Weaver R, Reiling L, Feng G, Drew D, Mueller I, Siba P . The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria. Sci Rep. 2016; 6:33094. PMC: 5015043. DOI: 10.1038/srep33094. View

Richards J, Arumugam T, Reiling L, Healer J, Hodder A, Fowkes F . Identification and prioritization of merozoite antigens as targets of protective human immunity to Plasmodium falciparum malaria for vaccine and biomarker development. J Immunol. 2013; 191(2):795-809. PMC: 3702023. DOI: 10.4049/jimmunol.1300778. View

Stanisic D, Fowkes F, Koinari M, Javati S, Lin E, Kiniboro B . Acquisition of antibodies against Plasmodium falciparum merozoites and malaria immunity in young children and the influence of age, force of infection, and magnitude of response. Infect Immun. 2014; 83(2):646-60. PMC: 4294228. DOI: 10.1128/IAI.02398-14. View

Mendis K, Rietveld A, Warsame M, Bosman A, Greenwood B, Wernsdorfer W . From malaria control to eradication: The WHO perspective. Trop Med Int Health. 2009; 14(7):802-9. DOI: 10.1111/j.1365-3156.2009.02287.x. View

Jin J, Tarrant R, Bolam E, Angell-Manning P, Soegaard M, Pattinson D . Production, quality control, stability, and potency of cGMP-produced RH5.1 protein vaccine expressed in S2 cells. NPJ Vaccines. 2018; 3:32. PMC: 6098134. DOI: 10.1038/s41541-018-0071-7. View

Opi D, Kurtovic L, Chan J, Horton J, Feng G, Beeson J . Multi-functional antibody profiling for malaria vaccine development and evaluation. Expert Rev Vaccines. 2021; 20(10):1257-1272. DOI: 10.1080/14760584.2021.1981864. View

10.

Nziza N, Tran T, DeRiso E, Dolatshahi S, Herman J, de Lacerda L . Accumulation of Neutrophil Phagocytic Antibody Features Tracks With Naturally Acquired Immunity Against Malaria in Children. J Infect Dis. 2023; 228(6):759-768. PMC: 10503956. DOI: 10.1093/infdis/jiad115. View

11.

Feng G, Wines B, Kurtovic L, Chan J, Boeuf P, Mollard V . Mechanisms and targets of Fcγ-receptor mediated immunity to malaria sporozoites. Nat Commun. 2021; 12(1):1742. PMC: 7979888. DOI: 10.1038/s41467-021-21998-4. View

12.

Challenger J, Olivera Mesa D, Da D, Yerbanga R, Lefevre T, Cohuet A . Predicting the public health impact of a malaria transmission-blocking vaccine. Nat Commun. 2021; 12(1):1494. PMC: 7940395. DOI: 10.1038/s41467-021-21775-3. View

13.

Walker M, Knudsen A, Partey F, Bassi M, Frank A, Castberg F . Acquisition and decay of IgM and IgG responses to merozoite antigens after Plasmodium falciparum malaria in Ghanaian children. PLoS One. 2020; 15(12):e0243943. PMC: 7746192. DOI: 10.1371/journal.pone.0243943. View

14.

Stanisic D, Good M . Malaria Vaccines: Progress to Date. BioDrugs. 2023; 37(6):737-756. PMC: 10581939. DOI: 10.1007/s40259-023-00623-4. View

15.

Mutanda A, Cheruiyot P, Hodges J, Ayodo G, Odero W, John C . Sensitivity of fever for diagnosis of clinical malaria in a Kenyan area of unstable, low malaria transmission. Malar J. 2014; 13:163. PMC: 4021053. DOI: 10.1186/1475-2875-13-163. View

16.

Boyle M, Reiling L, Osier F, Fowkes F . Recent insights into humoral immunity targeting Plasmodium falciparum and Plasmodium vivax malaria. Int J Parasitol. 2016; 47(2-3):99-104. PMC: 7004821. DOI: 10.1016/j.ijpara.2016.06.002. View

17.

Chan J, Wetzel D, Reiling L, Miura K, Drew D, Gilson P . Malaria vaccine candidates displayed on novel virus-like particles are immunogenic and induce transmission-blocking activity. PLoS One. 2019; 14(9):e0221733. PMC: 6736250. DOI: 10.1371/journal.pone.0221733. View

18.

Hamre K, Ondigo B, Hodges J, Dutta S, Theisen M, Ayodo G . Antibody Correlates of Protection from Clinical Malaria in an Area of Low and Unstable Malaria Transmission. Am J Trop Med Hyg. 2020; 103(6):2174-2182. PMC: 7695051. DOI: 10.4269/ajtmh.18-0805. View

19.

Reiling L, Richards J, Fowkes F, Barry A, Triglia T, Chokejindachai W . Evidence that the erythrocyte invasion ligand PfRh2 is a target of protective immunity against Plasmodium falciparum malaria. J Immunol. 2010; 185(10):6157-67. DOI: 10.4049/jimmunol.1001555. View

20.

Taylor R, Allen S, Greenwood B, Riley E . IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria. Am J Trop Med Hyg. 1998; 58(4):406-13. DOI: 10.4269/ajtmh.1998.58.406. View