Search

Malaria is caused by Plasmodium parasites and was responsible for over 247 million infections and 619,000 deaths in 2021. Radiation-attenuated sporozoite (RAS) vaccines can completely prevent blood stage infection by inducing protective liver-resident memory CD8 + T cells. 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. The ID route may offer significant translational advantages over the IV route and could improve sporozoite vaccine development., Competing Interests: Disclosures: S. C. M. filed a patent application on selected aspects of the prime-and-trap concept through the University of Washington. S. C. M. has equity in a startup company (Sound Vaccines, Inc.) that is negotiating with the University of Washington for rights to this intellectual property. The relationship between the authors and Sound Vaccines, Inc., has been reviewed by the University of Washington and complies with all University and State of Washington policies on such activities. S. C., B. K. L. S., and S. L. H. are paid employees of Sanaria Inc. M. T., S. C., and S. L. H. are inventors on two patents related to 7DW8-5 and Plasmodium SPZ, both of which are assigned in part to Sanaria Inc.– (1) Title: Pharmaceutical Compositions Comprising Attenuated Sporozoites and Glycolipid Adjuvants. Inventors: Chakravarty, Hoffman, and Tsuji. Date of Filing: October 28, 2013, Date of Issue: March 8, 2016. US Patent Issue Number: 9,278,125. (2) Title: Pharmaceutical Compositions Comprising Attenuated Sporozoites and Glycolipid Adjuvants (methods of use). Inventors: Chakravarty, Hoffman, and Tsuji. Date of Filing: February 18, 2016, Date of Issue: May 9, 2017. US Patent Issue Number: 9,642,909. M. T. is also an inventor of four patents related to 7DW8-5, all of which are assigned to Rockefeller University. (1) Glycolipids and analogues thereof as antigens for NK T cells. Date of Issue: May 19, 2009. US Patent Issue Number: 7,534,434. (2) Glycolipids and analogues thereof as antigens for NK T cells. Date of Issue: April 12, 2011. US Patent Issue Number: 7,923,013. (3) Glycolipids and analogues thereof as antigens for NK T cells. Date of Issue: April 24, 2012. US Patent Issue Number: 8,163,290 B2. (4) Glycolipids and analogues thereof as antigens for NK T cells. Date of Issue: November 19, 2013.US Patent Issue Number: 8,586,051. The other authors have no financial conflicts of interest.