Research Article: Advancing Global Health through Development and Clinical Trials Partnerships: A Randomized, Placebo-Controlled, Double-Blind Assessment of Safety, Tolerability, and Immunogenicity of PfSPZ Vaccine for Malaria in Healthy Equatoguinean Men

Date Published: January 30, 2018

Publisher: The American Society of Tropical Medicine and Hygiene

Author(s): Ally Olotu, Vicente Urbano, Ali Hamad, Martin Eka, Mwajuma Chemba, Elizabeth Nyakarungu, Jose Raso, Esther Eburi, Dolores O. Mandumbi, Dianna Hergott, Carl D. Maas, Mitoha O. Ayekaba, Diosdado N. Milang, Matilde R. Rivas, Tobias Schindler, Oscar M. Embon, Adam J. Ruben, Elizabeth Saverino, Yonas Abebe, Natasha KC, Eric R. James, Tooba Murshedkar, Anita Manoj, Sumana Chakravarty, Minglin Li, Matthew Adams, Christopher Schwabe, J. Luis Segura, Claudia Daubenberger, Marcel Tanner, Thomas L. Richie, Peter F. Billingsley, B. Kim Lee Sim, Salim Abdulla, Stephen L. Hoffman.

http://doi.org/10.4269/ajtmh.17-0449

Abstract

Equatorial Guinea (EG) has implemented a successful malaria control program on Bioko Island. A highly effective vaccine would be an ideal complement to this effort and could lead to halting transmission and eliminating malaria. Sanaria® PfSPZ Vaccine (Plasmodium falciparum sporozoite Vaccine) is being developed for this purpose. To begin the process of establishing the efficacy of and implementing a PfSPZ Vaccine mass vaccination program in EG, we decided to conduct a series of clinical trials of PfSPZ Vaccine on Bioko Island. Because no clinical trial had ever been conducted in EG, we first successfully established the ethical, regulatory, quality, and clinical foundation for conducting trials. We now report the safety, tolerability, and immunogenicity results of the first clinical trial in the history of the country. Thirty adult males were randomized in the ratio 2:1 to receive three doses of 2.7 × 105 PfSPZ of PfSPZ Vaccine (N = 20) or normal saline placebo (N = 10) by direct venous inoculation at 8-week intervals. The vaccine was safe and well tolerated. Seventy percent, 65%, and 45% of vaccinees developed antibodies to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) by enzyme-linked immunosorbent assay, PfSPZ by automated immunofluorescence assay, and PfSPZ by inhibition of sporozoite invasion assay, respectively. Antibody responses were significantly lower than responses in U.S. adults who received the same dosage regimen, but not significantly different than responses in young adult Malians. Based on these results, a clinical trial enrolling 135 subjects aged 6 months to 65 years has been initiated in EG; it includes PfSPZ Vaccine and first assessment in Africa of PfSPZ-CVac. ClinicalTrials.gov identifier: NCT02418962.

Partial Text

Malaria has major public health significance in sub-Saharan Africa.1 World Health Organization-Global Technical Strategy has set a goal of eliminating malaria from at least 10 malaria-endemic countries by the year 2020.2 Development and deployment of new tools such as highly efficacious malaria vaccines that can interrupt malaria transmission will be essential to achieve this goal. The RTS,S/AS01 candidate malaria vaccine has shown moderate efficacy against clinical disease in young children,3 but its limited efficacy against infection and significant adverse events (AEs) restrict its usefulness for malaria elimination.4,5

We have conducted the first clinical trial in the history of EG. There were significant regulatory, quality, clinical, and logistical challenges in conducting this trial fully adhering to the international standards of Good Clinical Practices. A detailed report of these developments and capacity building efforts will be published elsewhere. The trial was successful in showing that three doses of 2.7 × 105 PfSPZ of PfSPZ Vaccine were safe, well tolerated, and moderately immunogenic in healthy 18–35-year-old male Equatoguineans living in an area with low malaria exposure.

 

Source:

http://doi.org/10.4269/ajtmh.17-0449

 

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