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-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.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
The authors thank the vaccine trials participants for their contribution and commitment to vaccine research. We acknowledge the contributions of: our US National Institutes of Health (NIH) Clinical Center (CC) and National Institute of Allergy and Infectious Diseases (NIAID) colleagues, especially J. Stein, J. Pierson, R. Eckes, P. Driscoll, L. Ediger, and the nursing staff of the 5NW, SCSU, 5SE-S, and 5SE-N units; our VRC colleagues, especially A. Mittelman, H. Harvey, M. Young, C. Artis, R. Hicks, P. Darrah, and T. Abram; our Sanaria and Protein Potential colleagues, especially Y. Abebe, J. Jackson, A. Awe, M. King, H. Huang, A. Patil, S. Matheny, J. Overby, Y. Wen, K. Nelson, V. Pich, M. Orozco, D. Padilla, E. Saverino, B. Jiang, L. Gao, R. Xu, E. Fomumbod, M. Laskowski, T.T. Wai, F. Beams, R. Thompson, and A. Hoffman for administrative, operations, and legal support, and T. Luke for insight and inspiration; the EMMES Corporation; the NIAID Institutional Review Board; the NIAID Office of Communications and Government Relations; the NIH CC Department of Laboratory Medicine; the NIH CC IND Pharmacy, and the NIH CC Patient Recruitment and Public Liaison Office. We appreciate the expert reviews of the Safety Monitoring Committee (A. Durbin, K. Kester, and A. Cross) and the assistance from the US Military Malaria Vaccine Program, the Walter Reed Army Institute of Research Entomology Branch, and the Naval Medical Research Center (NMRC), especially A. Reyes, Y. Alcorta, G. Banania, C. Fedders, M. Dowler, T. Savransky, D. Patel, C. Brando, K. Kobylinski, and K. Walker. This work was supported by the intramural research program of the VRC, NIAID, NIH. Production and characterization of the PfSPZ Vaccine were supported in part by NIAID Small Business Innovation Research grants 5R44AI055229-11 (S.L.H.), 5R44AI058499-08 (S.L.H.), and 5R44AI058375-08 (S.L.H.). The humanized mouse experiments reported here were funded by the Bill and Melinda Gates Foundation (Investment ID: 24922; to S.H.I.K.).
The findings and conclusions in this report are those of the authors and do not necessarily reflect the views of the funding agency or collaborators. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, the Department of the Army, the Department of Defense, or the US Government. This work was supported in part by work unit number 6000.RADI.F.A0309 to NMRC. J.E.E. and S.A.D. are military service members, and this work was prepared as part of their official duties. Title 17 U.S.C. §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person's official duties.
Supplementary Figures 1–11 and Supplementary Tables 1–7
About this article
European Journal of Medicinal Chemistry (2019)