Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites

Sarah Lapidus; Morgan M Goheen; Mouhamad Sy; Awa B Deme; Ibrahima Mbaye Ndiaye; Younous Diedhiou; Amadou Moctar Mbaye; Kelly A Hagadorn; Seynabou Diouf Sene; Mariama Nicole Pouye; Laty Gaye Thiam; Aboubacar Ba; Noemi Guerra; Alassane Mbengue; Hamidah Raduwan; Jacqueline Gagnon; Inés Vigan-Womas; Sunil Parikh; Albert I Ko; Daouda Ndiaye; Erol Fikrig; Yu-Min Chuang; Amy K Bei

doi:10.1093/infdis/jiae525

Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to P. falciparum infected mosquito bites

J Infect Dis. 2024 Oct 30:jiae525. doi: 10.1093/infdis/jiae525. Online ahead of print.

Authors

Sarah Lapidus¹, Morgan M Goheen^{1

2}, Mouhamad Sy^{3

4}, Awa B Deme^{3

4}, Ibrahima Mbaye Ndiaye^{3

4}, Younous Diedhiou^{3

4}, Amadou Moctar Mbaye^{3

4}, Kelly A Hagadorn¹, Seynabou Diouf Sene⁵, Mariama Nicole Pouye⁵, Laty Gaye Thiam⁵, Aboubacar Ba⁵, Noemi Guerra¹, Alassane Mbengue⁵, Hamidah Raduwan², Jacqueline Gagnon⁵, Inés Vigan-Womas⁶, Sunil Parikh^{1

2}, Albert I Ko^{1

2}, Daouda Ndiaye^{3

4}, Erol Fikrig², Yu-Min Chuang², Amy K Bei^{1

3

5}

Affiliations

¹ Department of Epidemiology of Microbial Diseases, Yale School of Public Health, 60 College Street, New Haven, CT, 06510, USA.
² Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
³ Laboratory of Parasitology and Mycology, Cheikh Anta Diop University, Aristide le Dantec Hospital, Dakar, Senegal.
⁴ International Research and Training Center for Applied Genomics and Health Surveillance (CIGASS) at UCAD, Dakar, Senegal.
⁵ L2 Diagnostics, LLC. New Haven, CT, USA.
⁶ G4 - Malaria Experimental Genetic Approaches & Vaccines, Pôle Immunophysiopathologie et Maladies Infectieuses, Institut Pasteur de Dakar, Dakar, Senegal.

PMID: 39475423
DOI: 10.1093/infdis/jiae525

Abstract

Background: Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins like SG6 have been used as biomarkers of exposure to Anopheles mosquito bites. Here, we investigate four mosquito salivary proteins as potential biomarkers of human exposure to mosquitoes infected with P. falciparum: mosGILT, SAMSP1, AgSAP, and AgTRIO.

Methods: We tested population-level human immune responses in longitudinal and cross-sectional plasma from individuals with known P. falciparum infection from low and moderate transmission areas in Senegal using a multiplexed magnetic bead-based assay.

Results: AgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate endemic area, and to AgTRIO in both low and moderate endemic areas, were significantly higher than responses in a healthy non-endemic control cohort (p-values = 0.0245, 0.0064, and <0.0001 respectively). No antibody responses significantly differed between the low and moderate transmission area, or between equivalent groups during and outside the malaria transmission seasons. For AgSAP and AgTRIO, reactivity peaked 2-4 weeks after clinical P. falciparum infection and declined 3 months after infection.

Discussion: Reactivity to AgSAP and AgTRIO peaked after infection, with no differences between transmission seasons within region or between low and moderate transmission regions. This suggests that reactivity reflects exposure to infectious mosquitoes or recent bites rather than general mosquito exposure. Kinetics suggest reactivity is relatively short-lived. AgSAP and AgTRIO are promising candidates to incorporate into multiplexed assays for serosurveillance of population-level changes in P. falciparum-infected mosquito exposure.

Keywords: Anopheles; Plasmodium falciparum; Multiplex; Serosurveillance; salivary antigens; transmission.