Immunogenicity and Protective Efficacy of Radiation-Attenuated and Chemo-Attenuated PfSPZ Vaccines in Equatoguinean Adults
Said Jongo, Vicente Urbano, L. W. Preston Church, Ally Olotu, Stephen R. Manock, Tobias Schindler, Ali Mtoro, Natasha KC, Ali Hamad, Elizabeth Nyakarungu, Maxmillian Mpina, Anna Deal, José Raso Bijeri, Martín Eká Ondó Mangue, Beltrán Ekua Ntutumu Pasialo, Genaro Nsue Nguema, Salomon Nguema Owono, Matilde Riloha Rivas, Mwajuma Chemba, Kamaka R. Kassim, Eric R. James, Thomas C. Stabler, Yonas Abebe, Elizabeth Saverino, Julian Sax, Salome Hosch, Anneth Tumbo, Linda Gondwe, J. Luis Segura, Carlos Cortés Falla, Wonder P. Phiri, Dianna Hergott, Guillermo A. García, Christopher Schwabe, Carl Maas, Tooba Murshedkar, Peter F. Billingsley, Marcel Tanner, Mitoha Ondo’o Ayekaba, B. Kim Lee Sim, Claudia Daubenberger, Thomas L. Richie, Salim Abdulla, Stephen L. Hoffman
Abstract
ABSTRACT Plasmodium falciparum sporozoite (PfSPZ) Vaccine (radiation-attenuated, aseptic, purified, cryopreserved PfSPZ) and PfSPZ-CVac (infectious, aseptic, purified, cryopreserved PfSPZ administered to subjects taking weekly chloroquine chemoprophylaxis) have shown vaccine efficacies (VEs) of 100% against homologous controlled human malaria infection (CHMI) in nonimmune adults. Plasmodium falciparum sporozoite-CVac has never been assessed against CHMI in African vaccinees. We assessed the safety, immunogenicity, and VE against homologous CHMI of three doses of 2.7 × 10 6 PfSPZ of PfSPZ Vaccine at 8-week intervals and three doses of 1.0 × 10 5 PfSPZ of PfSPZ-CVac at 4-week intervals with each arm randomized, double-blind, placebo-controlled, and conducted in parallel. There were no differences in solicited adverse events between vaccinees and normal saline controls, or between PfSPZ Vaccine and PfSPZ-CVac recipients during the 6 days after administration of investigational product. However, from days 7–13, PfSPZ-CVac recipients had significantly more AEs, probably because of Pf parasitemia. Antibody responses were 2.9 times higher in PfSPZ Vaccine recipients than PfSPZ-CVac recipients at time of CHMI. Vaccine efficacy at a median of 14 weeks after last PfSPZ-CVac dose was 55% (8 of 13, P = 0.051) and at a median of 15 weeks after last PfSPZ Vaccine dose was 27% (5 of 15, P = 0.32). The higher VE in PfSPZ-CVac recipients of 55% with a 27-fold lower dose was likely a result of later stage parasite maturation in the liver, leading to induction of cellular immunity against a greater quantity and broader array of antigens.