Protection Against Malaria by Intravenous Immunization with a Nonreplicating Sporozoite Vaccine
Creators
- Seder, R. A.
- Chang, L.-J.
- Enama, M. E.
- Zephir, K. L.
- Sarwar, U. N.
- Gordon, I. J.
- Holman, L. A.
- James, E. R.
- Billingsley, P. F.
- Gunasekera, A.
- Richman, A.
- Chakravarty, S.
- Manoj, A.
- Velmurugan, S.
- Li, M.
- Ruben, A. J.
- Li, T.
- Eappen, A. G.
- Stafford, R. E.
- Plummer, S. H.
- Hendel, C. S.
- Novik, L.
- Costner, P. J. M.
- Mendoza, F. H.
- Saunders, J. G.
- Nason, M. C.
- Richardson, J. H.
- Murphy, J.
- Davidson, S. A.
- Richie, T. L.
- Sedegah, M.
- Sutamihardja, A.
- Fahle, G. A.
- Lyke, K. E.
- Laurens, M. B.
- Roederer, M.
- Tewari, K.
- Epstein, J. E.
- Sim, B. K. L.
- Ledgerwood, J. E.
- Graham, B. S.
- Hoffman, S. L.
- DiGiovanni, C.
- Williams, P.
- Luongo, N.
- Mitchell, J.
- Florez, M. B.
- Larkin, B.
- Berkowitz, N.
- Wilson, B.
- Clarke, T.
- Vasilenko, O.
- Yamshchikov, G.
- Sitar, S.
- Stanford, L.
- Pittman, I.
- Bailer, R. T.
- Casazza, J.
- Decederfelt, H.
- Starling, J.
- Williams, E. C.
- Lau, A.
- Antonara, S.
- Brocious, J.
- Kemp, M.
- Inglese, J.
- Dranchak, P.
- Abot, E. N.
- Reyes, S.
- Ganeshan, H.
- Belmonte, M.
- Huang, J.
- Belmonte, A.
- Komisar, J.
- Abebe, Y.
- Getachew, Y.
- Patil, A.
- Matheny, S.
- Nelson, K.
- Overby, J.
- Pich, V.
- Wen, Y.
- Fan, R.
- Fomumbod, E.
- Awe, A.
- Chakiath, C.
- King, M.
- Orozco, M. S.
- Murshedkar, T.
- Padilla, D.
- Jiang, B.
- Gao, L.
- Kc, N.
- Xu, R.
- Adams, M.
- Plowe, C.
- Loblein, H.
- Renehan, P. Z.
- Kunchai, M.
- Diep, L.
Description
Malaria Sporozoite Vaccine Each year, hundreds of millions of people are infected with Plasmodium falciparum, the mosquito-borne parasite that causes malaria. A preventative vaccine is greatly needed. Seder et al. (p. 1359, published online 8 August; see the Perspective by Good) now report the results from a phase I clinical trial where subjects were immunized intravenously with a whole, attenuated sporozoite vaccine. Three of 9 subjects who received four doses and zero of 6 subjects who received five doses of the vaccine went on to develop malaria after controlled malaria infection. Both antibody titers and cellular immune responses correlated positively with the dose of vaccine received, suggesting that both arms of the adaptive immune response may have participated in the observed protection. Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine—composed of attenuated, aseptic, purified, cryopreserved PfSPZ—was safe and wel-tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 105 PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards. Intravenous immunization with an attenuated whole malaria sporozoite vaccine protected volunteers in a phase I clinical trial. [Also see Perspective by Good] Intravenous immunization with an attenuated whole malaria sporozoite vaccine protected volunteers in a phase I clinical trial. [Also see Perspective by Good]
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