Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection

Authors: Kirsten E. Lyke, Andrew S. Ishizuka, Andrea A. Berry, Sumana Chakravarty, Adam DeZure, Mary E. Enama, Eric R. James, Peter F. Billingsley, Anusha Gunasekera, Anita Manoj, Minglin Li, Adam J. Ruben, Tao Li, Abraham G. Eappen, R. E. Stafford, Natasha KC, Tooba Murshedkar, Floreliz Mendoza, Ingelise J. Gordon, Kathryn L. Zephir, LaSonji A. Holman, Sarah H. Plummer, Cynthia S. Hendel, Laura Novik, Pamela Costner, Jamie Saunders, Nina M. Berkowitz, Barbara J. Flynn, Martha Nason, Lindsay S. Garver, Matthew B. Laurens, Christopher V. Plowe, Thomas L. Richie, Barney S. Graham, Mario Roederer, B. Kim Lee Sim, Julie E. Ledgerwood, Stephen L. Hoffman, Robert A. Seder - Proceedings of the National Academy of Sciences, PNAS 2017 cited by 253

= 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36-99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ-specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations.