Ultra-low volume intradermal administration of radiation-attenuated sporozoites with the glycolipid adjuvant 7DW8-5 completely protects mice against malaria.
Felicia N Watson, Melanie J Shears, Anya C Kalata, Caroline J Duncombe, A Mariko Seilie, Chris Chavtur, Ethan Conrad, Irene Cruz Talavera, Andrew Raappana, D Noah Sather, Sumana Chakravarty, B Kim Lee Sim, Stephen L Hoffman, Moriya Tsuji, Sean C Murphy
Author Information
Felicia N Watson: Graduate Program in Pathobiology, Department of Global Health, University of Washington, Seattle, WA, 98109, USA.
Melanie J Shears: Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA.
Anya C Kalata: Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA.
Caroline J Duncombe: Graduate Program in Pathobiology, Department of Global Health, University of Washington, Seattle, WA, 98109, USA.
A Mariko Seilie: Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA.
Chris Chavtur: Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA.
Ethan Conrad: Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA.
Irene Cruz Talavera: Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA.
Andrew Raappana: Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, 98109, USA.
D Noah Sather: Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, 98109, USA.
Sumana Chakravarty: Sanaria Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA.
B Kim Lee Sim: Sanaria Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA.
Stephen L Hoffman: Sanaria Inc., 9800 Medical Center Drive, Suite A209, Rockville, MD, 20850, USA.
Moriya Tsuji: Aaron Diamond AIDS Research Center, Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Sean C Murphy: Graduate Program in Pathobiology, Department of Global Health, University of Washington, Seattle, WA, 98109, USA. murphysc@uw.edu.
Radiation-attenuated sporozoite (RAS) vaccines can completely prevent blood stage Plasmodium infection by inducing liver-resident memory CD8 T cells to target parasites in the liver. Such T cells can be induced by 'Prime-and-trap' vaccination, which here combines DNA priming against the P. yoelii circumsporozoite protein (CSP) with a subsequent intravenous (IV) dose of liver-homing RAS to "trap" the activated and expanding T cells in the liver. Prime-and-trap confers durable protection in mice, and efforts are underway to translate this vaccine strategy to the clinic. However, it is unclear whether the RAS trapping dose must be strictly administered by the IV route. Here we show that intradermal (ID) RAS administration can be as effective as IV administration if RAS are co-administrated with the glycolipid adjuvant 7DW8-5 in an ultra-low inoculation volume. In mice, the co-administration of RAS and 7DW8-5 in ultra-low ID volumes (2.5 µL) was completely protective and dose sparing compared to standard volumes (10-50 µL) and induced protective levels of CSP-specific CD8 T cells in the liver. Our finding that adjuvants and ultra-low volumes are required for ID RAS efficacy may explain why prior reports about higher volumes of unadjuvanted ID RAS proved less effective than IV RAS. The ID route may offer significant translational advantages over the IV route and could improve sporozoite vaccine development.
References
Cell Host Microbe. 2021 May 12;29(5):752-756.e4
[PMID: 33857426]
