Safety and protective efficacy of PfSPZ Vaccine administered to HIV-negative and -positive Tanzanian adults

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Abstract

BACKGROUND Sanaria PfSPZ Vaccine, composed of attenuated Plasmodium falciparum (Pf) sporozoites (SPZ), protects against malaria. We conducted this clinical trial to assess the safety and efficacy of PfSPZ Vaccine in HIV-positive (HIV+) individuals, since the HIV-infection status of participants in mass vaccination programs may be unknown.METHODS This randomized, double-blind, placebo-controlled trial enrolled 18- to 45-year-old HIV-negative (HIV–) and well-controlled HIV+ Tanzanians (HIV viral load <40 copies/mL, CD4 counts >500 cells/μL). Participants received 5 doses of PfSPZ Vaccine or normal saline (NS) over 28 days, followed by controlled human malaria infection (CHMI) 3 weeks later.RESULTS There were no solicited adverse events in the 9 HIV– and 12 HIV+ participants. After CHMI, 6 of 6 NS controls, 1 of 5 HIV– vaccinees, and 4 of 4 HIV+ vaccinees were Pf positive by quantitative PCR (qPCR). After immunization, anti–Pf circumsporozoite protein (anti-PfCSP) (isotype and IgG subclass) and anti-PfSPZ antibodies, anti-PfSPZ CD4+ T cell responses, and Vδ2+ γδ CD3+ T cells were nonsignificantly higher in HIV– than in HIV+ vaccinees. Sera from HIV– vaccinees had significantly higher inhibition of PfSPZ invasion of hepatocytes in vitro and antibody-dependent complement deposition (ADCD) and Fcγ3B binding by anti-PfCSP and ADCD by anti–cell-traversal protein for ookinetes and SPZ (anti-PfCelTOS) antibodies.CONCLUSIONS PfSPZ Vaccine was safe and well tolerated in HIV+ vaccinees, but not protective. Vaccine efficacy was 80% in HIV– vaccinees (P = 0.012), whose sera had significantly higher inhibition of PfSPZ invasion of hepatocytes and enrichment of multifunctional PfCSP antibodies. A more potent PfSPZ vaccine or regimen is needed to protect those living with HIV against Pf infection in Africa.TRIAL REGISTRATION ClinicalTrials.gov NCT03420053.FUNDING Equatorial Guinea Malaria Vaccine Initiative (EGMVI), made up of the Government of Equatorial Guinea Ministries of Mines and Hydrocarbons, and Health and Social Welfare, Marathon Equatorial Guinea Production Limited, Noble Energy, Atlantic Methanol Production Company, and EG LNG; Swiss government, through ESKAS scholarship grant no. 2016.0056; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH; NIH grant 1U01AI155354-01.

Authors

Said Jongo, L.W. Preston Church, Florence Milando, Munira Qassim, Tobias Schindler, Mohammed Rashid, Anneth Tumbo, Gloria Nyaulingo, Bakari M. Bakari, Thabit Athuman Mbaga, Latipha Mohamed, Kamaka Kassimu, Beatus S. Simon, Maxmillian Mpina, Irfan Zaidi, Patrick E. Duffy, Phillip A. Swanson II, Robert Seder, Jonathan D. Herman, Maanasa Mendu, Yonatan Zur, Galit Alter, Natasha KC, Pouria Riyahi, Yonas Abebe, Tooba Murshedkar, Eric R. James, Peter F. Billingsley, B. Kim Lee Sim, Thomas L. Richie, Claudia Daubenberger, Salim Abdulla, Stephen L. Hoffman