Human to Mouse Antibody Transfer in FRG Mice

Protection Against Malaria at 1 Year and Immune Correlates Following PfSPZ Vaccination

Ishizuka et. al, 2016

Study Summary

In this study, researchers from the NIH and Sanaria transferred antibodies from people vaccinated with a new attenuated parasite into liver humanized FRG mice. Next, the FRG mice were challenged by allowing malaria infected mosquitoes to feed on them. The parasite strain to challenge the animals was genetically modified to express luciferase, which allows the researchers to easily quantify the infection by measuring in vivo luminescence. This study shows that antibodies are induced and are able to protect against malaria infection.

Andrew S Ishizuka, Kirsten E Lyke, Adam DeZure, Andrea A Berry, Thomas L Richie, Floreliz H Mendoza, Mary E Enama, Ingelise J Gordon, Lee-Jah Chang, Uzma N Sarwar, Kathryn L Zephir, LaSonji A Holman, Eric R James, Peter F Billingsley, Anusha Gunasekera, Sumana Chakravarty, Anita Manoj, MingLin Li, Adam J Ruben, Tao Li, Abraham G Eappen, Richard E Stafford, Natasha K C, Tooba Murshedkar, Hope DeCederfelt, Sarah H Plummer, Cynthia S Hendel, Laura Novik, Pamela J M Costner, Jamie G Saunders, Matthew B Laurens, Christopher V Plowe, Barbara Flynn, William R Whalen, J P Todd, Jay Noor, Srinivas Rao, Kailan Sierra-Davidson, Geoffrey M Lynn, Judith E Epstein, Margaret A Kemp, Gary A Fahle, Sebastian A Mikolajczak, Matthew Fishbaugher, Brandon K Sack, Stefan H I Kappe, Silas A Davidson, Lindsey S Garver, Niklas K Björkström, Martha C Nason, Barney S Graham, Mario Roederer, B Kim Lee Sim, Stephen L Hoffman, Julie E Ledgerwood & Robert A Seder

 2016 Jun;22(6):614-23

Study Abstract

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 . 105 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-g-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.