PfSPZ Vaccine induces focused humoral immune response in HIV positive and negative Tanzanian adults
Year: 2024
Type: article
Abstract: BACKGROUND: PfSPZ Vaccine, a promising pre-erythrocytic stage malaria vaccine candidate based on whole, radiation-attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), has proven safe and effective in mediating sterile protection from malaria in malaria-naïve and exposed healthy adults. Vaccine-induced protection presumably depends on cellular responses to early parasite liver stages, but humoral immunity contributes. METHODS: On custom-made Pf protein microarrays, we profiled IgG and IgM responses to PfSPZ Vaccine and subsequent homologous controlled human malaria infection (CHMI) in 21 Tanzanian adults with (n = 12) or without (n = 9) HIV infection. Expression of the main identified immunogens in the pre-erythrocytic parasite stage was verified by immunofluorescence detection using freshly purified PfSPZ and an in vitro model of primary human hepatocytes. FINDINGS: Independent of HIV infection status, immunisation induced focused IgG and IgM responses to circumsporozoite surface protein (PfCSP) and merozoite surface protein 5 (PfMSP5). We show that PfMSP5 is detectable on the surface and in the apical complex of PfSPZ. INTERPRETATION: Our data demonstrate that HIV infection does not affect the quantity of the total IgG and IgM antibody responses to PfCSP and PfMSP5 after immunization with PfSPZ Vaccine. PfMSP5 represents a highly immunogenic, so far underexplored, target for vaccine-induced antibodies in malaria pre-exposed volunteers. FUNDING: This work was supported by the Equatorial Guinea Malaria Vaccine Initiative (EGMVI), the Clinical Trial Platform of the German Center for Infection Research (TTU 03.702), the Swiss Government Excellence Scholarships for Foreign Scholars and Artists (grant 2016.0056) and the Interdisciplinary Center for Clinical Research doctoral program of the Tübingen University Hospital. The funders had no role in design, analysis, or reporting of this study.
Source: EBioMedicine
Authors: Anneth Tumbo, Freia-Raphaella Lorenz, Annie S.P. Yang, Stephanie Sefried, Tobias Schindler, Maximilian Mpina, Jean-Pierre Dangy, Florence A. Milando, Mohammed A. Rashid, Gloria Nyaulingo, Kamaka Ramadhani, Said Jongo, Philip L. Felgner, Yonas Abebe, B. Kim Lee Sim, L.W. Preston Church, Thomas L. Richie, Peter F. Billingsley, Tooba Murshedkar, Stephen L. Hoffman, Salim Abdulla, Peter G. Kremsner, Benjamin Mordmüller, Claudia Daubenberger, Rolf Fendel
Institutions: Ifakara Health Institute, Swiss Tropical and Public Health Institute, University of Basel, Radboud University Medical Center, German Center for Infection Research, University of Tübingen, Radboud University Nijmegen, University of California, Irvine, Sanaria, Centre de Recherche Médicales de Lambaréné
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,000
Award: G1881230665
OpenAlex ID: W4402999325