PfSPZ Vaccine induces focused humoral immune response in HIV positive and negative Tanzanian adultsResearch in context
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
Affiliations
Anneth Tumbo
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; Ifakara Health Institute, Bagamoyo Branch, Bagamoyo, United Republic of Tanzania
Freia-Raphaella Lorenz
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Radboud Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany
Annie S.P. Yang
Radboud Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands
Stephanie Sefried
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany
Tobias Schindler
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland
Maximilian Mpina
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; Ifakara Health Institute, Bagamoyo Branch, Bagamoyo, United Republic of Tanzania
Jean-Pierre Dangy
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland
Florence A. Milando
Ifakara Health Institute, Bagamoyo Branch, Bagamoyo, United Republic of Tanzania
Mohammed A. Rashid
Ifakara Health Institute, Bagamoyo Branch, Bagamoyo, United Republic of Tanzania
Gloria Nyaulingo
Ifakara Health Institute, Bagamoyo Branch, Bagamoyo, United Republic of Tanzania
Kamaka Ramadhani
Ifakara Health Institute, Bagamoyo Branch, Bagamoyo, United Republic of Tanzania
Said Jongo
Ifakara Health Institute, Bagamoyo Branch, Bagamoyo, United Republic of Tanzania
Philip L. Felgner
University of California, Irvine, California, United States
Yonas Abebe
Sanaria Inc., Rockville, Maryland, United States
B. Kim Lee Sim
Sanaria Inc., Rockville, Maryland, United States
L.W. Preston Church
Sanaria Inc., Rockville, Maryland, United States
Thomas L. Richie
Sanaria Inc., Rockville, Maryland, United States
Peter F. Billingsley
Sanaria Inc., Rockville, Maryland, United States
Tooba Murshedkar
Sanaria Inc., Rockville, Maryland, United States
Stephen L. Hoffman
Sanaria Inc., Rockville, Maryland, United States
Salim Abdulla
Ifakara Health Institute, Bagamoyo Branch, Bagamoyo, United Republic of Tanzania
Peter G. Kremsner
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
Benjamin Mordmüller
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Radboud Center for Infectious Diseases, Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon
Claudia Daubenberger
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland; Corresponding author. Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
Rolf Fendel
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; German Center for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany; Centre de Recherches Médicales de Lambaréné, Lambaréné, Gabon; Corresponding author. Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
Summary: 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.
