Transgenic Plasmodium berghei expressing P. vivax pre-erythrocytic antigens SSP3 and SPECT1 to elucidate their efficacy towards vaccine development
- 1Center for Global Health and Interdisciplinary Research, College of Public Health, University of South Florida, Tampa, Florida, United States of America
- 2Leiden University Center for Infectious Diseases (LUCID), Leiden University Medical Center, Leiden, Netherlands
- 3Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom
Abstract
The development of an efficacious vaccine against Plasmodium vivax malaria remains a top global health priority. P. vivax forms hypnozoites, dormant forms of the parasite in the liver that can become reactivated after a few months or even years, causing relapse malaria and enhancing transmission. Therefore, targeting antigens expressed during the pre-erythrocytic stages offers the potential to prevent clinical malaria from both primary and relapse infections. The circumsporozoite protein (CSP) is the leading pre-erythrocytic vaccine candidate and forms the basis for the current P. falciparum malaria vaccines RTS, S and R21/Matrix M. Studies have shown that in P. vivax, CSP attributes limited protection, highlighting the need to identify additional pre-erythrocytic antigens to improve vaccine efficacy. Evaluation of new candidates often requires human volunteers, making initial screening complex and highlighting the need for robust preclinical models. In this study, we generated transgenic P. berghei parasite lines as research tools to investigate the potential efficacy of two P. vivax pre-erythrocytic vaccine candidates, SSP3 and SPECT1. The chimeric Pb-PvSSP3 and Pb-PvSPECT1 lines showed normal development throughout the parasite life cycle, in both mice and mosquitoes. Antisera raised against recombinant PvSSP3 and PvSPECT1 using TitreMax Gold adjuvant exhibited reduction in sporozoite invasion of hepatocytes in vitro, with mean inhibitions of 27% and 14%, respectively. In vivo sporozoite challenge studies showed sterile protection in 10% of mice immunized with rPvSPECT1, whereas rPvSSP3 provided no detectable protection. Although substantial protection was not observed for either antigen under the conditions tested, the transgenic P. berghei lines generated in this study serve as useful platforms for evaluating the efficacy of these antigens as vaccine candidates across different delivery systems and adjuvanted formulations. Author summary: Plasmodium vivax is the most geographically widespread human malaria parasite outside Africa. It presents a unique challenge by forming dormant liver stages called hypnozoites that can reactivate, leading to relapse of blood-stage infections and mosquito transmission. This complicates elimination efforts and maintains transmission reservoirs. Focusing on pre-erythrocytic vaccines that target the sporozoite and liver stages of P. vivax offers a promising strategy to prevent establishing the initial liver stage infection and reduce disease transmission. However, progress in developing a pre-erythrocytic P. vivax vaccine has been slow because of the lack of easily attainable laboratory-produced sporozoites to test its efficacy. Fortunately, transgenic rodent malaria parasites expressing P. vivax antigens provide reproducible challenge models for assessing vaccine-induced immunity in mice. In this study, we evaluated the efficacy of two novel P. vivax pre-erythrocytic candidates, SSP3 and SPECT1, using transgenic P. berghei strains expressing P. vivax SSP3 and SPECT1 by gene replacement. PvSSP3 and PvSPECT1 antisera inhibited hepatocyte invasion by transgenic sporozoites in vitro. However, preliminary results from in vivo challenge experiments provided 10% sterile protection with PvSPECT1 but no significant protection for PvSSP3. The transgenic P. berghei lines generated in this study can be used to evaluate the efficacy of these antigens through different delivery systems and adjuvanted vaccine formulations.
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BibTeX
@article{kolli2026transgenic,
title = {{Transgenic Plasmodium berghei expressing P. vivax pre-erythrocytic antigens SSP3 and SPECT1 to elucidate their efficacy towards vaccine development}},
author = {Surendra Kumar Kolli and Pradeep Annamalai Subramani and Jai Ramesar and Justin Nicholas and Madison M. Ogbondah and Samantha J. Barnes and Pooya Mahdavi and Ahmed M. Salman and Francis Babila Ntumngia and Chris J. Janse and John H. Adams},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = oct,
doi = {10.1371/journal.pntd.0014810},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014810},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Transgenic Plasmodium berghei expressing P. vivax pre-erythrocytic antigens SSP3 and SPECT1 to elucidate their efficacy towards vaccine development
AU - Surendra Kumar Kolli
AU - Pradeep Annamalai Subramani
AU - Jai Ramesar
AU - Justin Nicholas
AU - Madison M. Ogbondah
AU - Samantha J. Barnes
AU - Pooya Mahdavi
AU - Ahmed M. Salman
AU - Francis Babila Ntumngia
AU - Chris J. Janse
AU - John H. Adams
PY - 2026
DA - 2026/10/22
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014810
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014810
AB - The development of an efficacious vaccine against Plasmodium vivax malaria remains a top global health priority. P. vivax forms hypnozoites, dormant forms of the parasite in the liver that can become reactivated after a few months or even years, causing relapse malaria and enhancing transmission. Therefore, targeting antigens expressed during the pre-erythrocytic stages offers the potential to prevent clinical malaria from both primary and relapse infections. The circumsporozoite protein (CSP) is the leading pre-erythrocytic vaccine candidate and forms the basis for the current P. falciparum malaria vaccines RTS, S and R21/Matrix M. Studies have shown that in P. vivax, CSP attributes limited protection, highlighting the need to identify additional pre-erythrocytic antigens to improve vaccine efficacy. Evaluation of new candidates often requires human volunteers, making initial screening complex and highlighting the need for robust preclinical models. In this study, we generated transgenic P. berghei parasite lines as research tools to investigate the potential efficacy of two P. vivax pre-erythrocytic vaccine candidates, SSP3 and SPECT1. The chimeric Pb-PvSSP3 and Pb-PvSPECT1 lines showed normal development throughout the parasite life cycle, in both mice and mosquitoes. Antisera raised against recombinant PvSSP3 and PvSPECT1 using TitreMax Gold adjuvant exhibited reduction in sporozoite invasion of hepatocytes in vitro, with mean inhibitions of 27% and 14%, respectively. In vivo sporozoite challenge studies showed sterile protection in 10% of mice immunized with rPvSPECT1, whereas rPvSSP3 provided no detectable protection. Although substantial protection was not observed for either antigen under the conditions tested, the transgenic P. berghei lines generated in this study serve as useful platforms for evaluating the efficacy of these antigens as vaccine candidates across different delivery systems and adjuvanted formulations. Author summary: Plasmodium vivax is the most geographically widespread human malaria parasite outside Africa. It presents a unique challenge by forming dormant liver stages called hypnozoites that can reactivate, leading to relapse of blood-stage infections and mosquito transmission. This complicates elimination efforts and maintains transmission reservoirs. Focusing on pre-erythrocytic vaccines that target the sporozoite and liver stages of P. vivax offers a promising strategy to prevent establishing the initial liver stage infection and reduce disease transmission. However, progress in developing a pre-erythrocytic P. vivax vaccine has been slow because of the lack of easily attainable laboratory-produced sporozoites to test its efficacy. Fortunately, transgenic rodent malaria parasites expressing P. vivax antigens provide reproducible challenge models for assessing vaccine-induced immunity in mice. In this study, we evaluated the efficacy of two novel P. vivax pre-erythrocytic candidates, SSP3 and SPECT1, using transgenic P. berghei strains expressing P. vivax SSP3 and SPECT1 by gene replacement. PvSSP3 and PvSPECT1 antisera inhibited hepatocyte invasion by transgenic sporozoites in vitro. However, preliminary results from in vivo challenge experiments provided 10% sterile protection with PvSPECT1 but no significant protection for PvSSP3. The transgenic P. berghei lines generated in this study can be used to evaluate the efficacy of these antigens through different delivery systems and adjuvanted vaccine formulations.
SN - 1935-2735
ER -