Controlled human infection with Plasmodium falciparum-infected mosquito bites elicits antibodies against mosquito salivary protein SG1L3
4 affiliations
- 1Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands
- 2Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- 3Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom
- 4Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso
Abstract
Human malaria infections begin with the injection of Plasmodium sporozoites via mosquito saliva. Whole sporozoite immunizations have been used as a model to study immune responses to malaria parasites, having culminated in circumsporozoite protein (CSP)-targeting vaccines and monoclonal antibodies (mAbs). However, antibody responses targeting non-CSP antigens on the sporozoite surface remain poorly characterized. Here, we isolated single B cells from a human volunteer immunized by Plasmodium falciparum-infected mosquito bites, who had acquired non-CSP-specific antibodies that recognize sporozoites. We identified two mAbs that recognize the surface of P. falciparum sporozoites, but do not bind to CSP. Using immunoprecipitation followed by mass-spectrometry, we found that the target of these mAbs is not a P. falciparum protein but the mosquito salivary protein SG1L3. We observed that recombinant SG1L3 binds to P. falciparum sporozoites. However, the SG1L3-specific mAbs and SG1L3-specific polyclonal antibodies from this volunteer, as well as polyclonal antibodies raised against recombinant SG1L3 in rabbits, fail to block liver stage infection in vitro, making this an unlikely target for functional antibodies. We observed that inhabitants from an area with intense Anopheles exposure in Burkina Faso can have antibodies against SG1L3, and that antibody titers increase with age. In conclusion, we identified the first human mAbs against a mosquito saliva protein that binds to the surface of sporozoites. Future work should assess whether naturally acquired antibodies against this protein may be used as a serological marker of mosquito exposure. Author summary: Malaria infection starts when an infected mosquito injects its saliva, containing malaria parasites, into the skin. Antibody responses against the main malaria parasite surface protein have been well studied, and formed the basis for the development of this protein into the two malaria vaccines that are currently available. However, less is known about antibody responses against other parasite antigens. In this study, we analyzed antibody-producing cells from a volunteer who was immunized through bites of malaria-infected mosquitoes. We identified antibodies that bind to the surface of malaria parasites but, unexpectedly, do not recognize parasite proteins. Instead, these antibodies target a protein from mosquito saliva that binds to the parasite surface. Human and rabbit antibodies against this protein did not prevent infection in vitro. We found that people living in a malaria-endemic region of Burkina Faso developed antibodies against this mosquito salivary protein. This suggests that this protein may serve as a tool to monitor how often people are bitten by mosquitoes that spread malaria, which can be used to support malaria elimination campaigns.
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BibTeX
@article{andrade2026controlled,
title = {{Controlled human infection with Plasmodium falciparum-infected mosquito bites elicits antibodies against mosquito salivary protein SG1L3}},
author = {Carolina M. Andrade and Renate C. van Daalen and Amanda Fabra-García and Sanne Grievink and Geert-Jan van Gemert and Karina Teelen and Svenja S. Hester and Rianne Stoter and Marga van de Vegte-Bolmer and Chris Drakeley and Alfred B. Tiono and Robert W. Sauerwein and Teun Bousema and Matthijs M. Jore},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014719},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014719},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Controlled human infection with Plasmodium falciparum-infected mosquito bites elicits antibodies against mosquito salivary protein SG1L3
AU - Carolina M. Andrade
AU - Renate C. van Daalen
AU - Amanda Fabra-García
AU - Sanne Grievink
AU - Geert-Jan van Gemert
AU - Karina Teelen
AU - Svenja S. Hester
AU - Rianne Stoter
AU - Marga van de Vegte-Bolmer
AU - Chris Drakeley
AU - Alfred B. Tiono
AU - Robert W. Sauerwein
AU - Teun Bousema
AU - Matthijs M. Jore
PY - 2026
DA - 2026/10/28
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014719
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014719
AB - Human malaria infections begin with the injection of Plasmodium sporozoites via mosquito saliva. Whole sporozoite immunizations have been used as a model to study immune responses to malaria parasites, having culminated in circumsporozoite protein (CSP)-targeting vaccines and monoclonal antibodies (mAbs). However, antibody responses targeting non-CSP antigens on the sporozoite surface remain poorly characterized. Here, we isolated single B cells from a human volunteer immunized by Plasmodium falciparum-infected mosquito bites, who had acquired non-CSP-specific antibodies that recognize sporozoites. We identified two mAbs that recognize the surface of P. falciparum sporozoites, but do not bind to CSP. Using immunoprecipitation followed by mass-spectrometry, we found that the target of these mAbs is not a P. falciparum protein but the mosquito salivary protein SG1L3. We observed that recombinant SG1L3 binds to P. falciparum sporozoites. However, the SG1L3-specific mAbs and SG1L3-specific polyclonal antibodies from this volunteer, as well as polyclonal antibodies raised against recombinant SG1L3 in rabbits, fail to block liver stage infection in vitro, making this an unlikely target for functional antibodies. We observed that inhabitants from an area with intense Anopheles exposure in Burkina Faso can have antibodies against SG1L3, and that antibody titers increase with age. In conclusion, we identified the first human mAbs against a mosquito saliva protein that binds to the surface of sporozoites. Future work should assess whether naturally acquired antibodies against this protein may be used as a serological marker of mosquito exposure. Author summary: Malaria infection starts when an infected mosquito injects its saliva, containing malaria parasites, into the skin. Antibody responses against the main malaria parasite surface protein have been well studied, and formed the basis for the development of this protein into the two malaria vaccines that are currently available. However, less is known about antibody responses against other parasite antigens. In this study, we analyzed antibody-producing cells from a volunteer who was immunized through bites of malaria-infected mosquitoes. We identified antibodies that bind to the surface of malaria parasites but, unexpectedly, do not recognize parasite proteins. Instead, these antibodies target a protein from mosquito saliva that binds to the parasite surface. Human and rabbit antibodies against this protein did not prevent infection in vitro. We found that people living in a malaria-endemic region of Burkina Faso developed antibodies against this mosquito salivary protein. This suggests that this protein may serve as a tool to monitor how often people are bitten by mosquitoes that spread malaria, which can be used to support malaria elimination campaigns.
SN - 1553-7374
SN - 1553-7366
ER -