Protection against malaria at 1 year and immune correlates following PfSPZ vaccination

• Published in: Nature medicine Vol. 22; no. 6; pp. 614 - 623
• Main Authors: Ishizuka, Andrew S, Lyke, Kirsten E, DeZure, Adam, Berry, Andrea A, Richie, Thomas L, Mendoza, Floreliz H, Enama, Mary E, Gordon, Ingelise J, Chang, Lee-Jah, Sarwar, Uzma N, Zephir, Kathryn L, Holman, LaSonji A, James, Eric R, Billingsley, Peter F, Gunasekera, Anusha, Chakravarty, Sumana, Manoj, Anita, Li, MingLin, Ruben, Adam J, Li, Tao, Eappen, Abraham G, Stafford, Richard E, K C, Natasha, Murshedkar, Tooba, DeCederfelt, Hope, Plummer, Sarah H, Hendel, Cynthia S, Novik, Laura, Costner, Pamela J M, Saunders, Jamie G, Laurens, Matthew B, Plowe, Christopher V, Flynn, Barbara, Whalen, William R, Todd, J P, Noor, Jay, Rao, Srinivas, Sierra-Davidson, Kailan, Lynn, Geoffrey M, Epstein, Judith E, Kemp, Margaret A, Fahle, Gary A, Mikolajczak, Sebastian A, Fishbaugher, Matthew, Sack, Brandon K, Kappe, Stefan H I, Davidson, Silas A, Garver, Lindsey S, Björkström, Niklas K, Nason, Martha C, Graham, Barney S, Roederer, Mario, Sim, B Kim Lee, Hoffman, Stephen L, Ledgerwood, Julie E, Seder, Robert A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2016; Nature Publishing Group
• Subjects: 13/31; 631/326/590; 64/60; 692/699/255/1629; Administration, Intravenous; Adolescent; Adult; Animals; Antibodies; Antibodies, Protozoan - immunology; Biomedicine; Blood; Cancer Research; Causes of; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Correlation; Dosage; Durability; Enzyme-Linked Immunosorbent Assay; Female; Healthy Volunteers; Hepatocytes; Humans; Immune system; Immunization; Immunogenicity, Vaccine - immunology; Immunoglobulin G - immunology; Infectious Diseases; Interferon-gamma - immunology; Liver; Liver - cytology; Liver - immunology; Lymphocytes; Lymphocytes T; Macaca mulatta; Malaria; Malaria vaccine; Malaria Vaccines - immunology; Malaria Vaccines - therapeutic use; Malaria, Falciparum - prevention & control; Male; Metabolic Diseases; Middle Aged; Molecular Medicine; Neurosciences; Parasitemia; Parasitemia - immunology; Parasitemia - prevention & control; Physiological aspects; Plasmodium falciparum; Plasmodium falciparum - immunology; Prevention; Primates; Sporozoites - immunology; T cells; T-Lymphocytes - immunology; Vaccination; Vaccines; Vector-borne diseases; Young Adult; γ-Interferon; United States
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/nm.4110

Fifty-five percent of individuals vaccinated with an attenuated Plasmodium falciparum sporozoite vaccine remained without parasitemia after controlled human malaria infection one year later; immune correlate analysis in humans and non-human primates suggest a role for liver-resident T cells. An attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) vaccine, PfSPZ Vaccine, is highly protective against controlled human malaria infection (CHMI) 3 weeks after immunization, but the durability of protection is unknown. We assessed how vaccine dosage, regimen, and route of administration affected durable protection in malaria-naive adults. After four intravenous immunizations with 2.7 × 10 5 PfSPZ, 6/11 (55%) vaccinated subjects remained without parasitemia following CHMI 21 weeks after immunization. Five non-parasitemic subjects from this dosage group underwent repeat CHMI at 59 weeks, and none developed parasitemia. Although Pf-specific serum antibody levels correlated with protection up to 21–25 weeks after immunization, antibody levels waned substantially by 59 weeks. Pf-specific T cell responses also declined in blood by 59 weeks. To determine whether T cell responses in blood reflected responses in liver, we vaccinated nonhuman primates with PfSPZ Vaccine. Pf-specific interferon-γ-producing CD8 T cells were present at ∼100-fold higher frequencies in liver than in blood. Our findings suggest that PfSPZ Vaccine conferred durable protection to malaria through long-lived tissue-resident T cells and that administration of higher doses may further enhance protection.