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NEW THIS TUESDAY: PROTECTION AGAINST MALARIA BY INTRAVENOUS IMMUNIZATION WITH A NONREPLICATING SPOROZOITE VACCINE

Monday, 12th of August 2013

• PROTECTION AGAINST MALARIA BY INTRAVENOUS IMMUNIZATION WITH A NONREPLICATING SPOROZOITE VACCINE

Sciencewww.sciencemag.org

Published Online August 8 2013

Research Article

Protection Against Malaria by Intravenous Immunization with a Nonreplicating Sporozoite Vaccine

Robert A. Seder1,*,†,

Lee-Jah Chang1,*,

Mary E. Enama1,

Kathryn L. Zephir1,

Uzma N. Sarwar1,

Ingelise J. Gordon1,

LaSonji A. Holman1,

Eric R. James2,

Peter F. Billingsley2,

Anusha Gunasekera2,

Adam Richman2,

Sumana Chakravarty2,

Anita Manoj2,

Soundarapandian Velmurugan2,

MingLin Li3,

Adam J. Ruben2,

Tao Li2,

Abraham G. Eappen2,

Richard E. Stafford2,3,

Sarah H. Plummer1,

Cynthia S. Hendel1,

Laura Novik1,

Pamela J.M. Costner1,

Floreliz H. Mendoza1,

Jamie G. Saunders1,

Martha C. Nason4,

Jason H. Richardson5,

Jittawadee Murphy5,

Silas A. Davidson5,

Thomas L. Richie6,

Martha Sedegah6,

Awalludin Sutamihardja6,

Gary A. Fahle7,

Kirsten E. Lyke8,

Matthew B. Laurens8,9,

Mario Roederer1,

Kavita Tewari1,

Judith E. Epstein6,

B. Kim Lee Sim2,3,

Julie E. Ledgerwood1,

Barney S. Graham1,‡,

Stephen L. Hoffman2,3,‡,

the VRC 312 Study Team§

+ Author Affiliations

1Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA.

2Sanaria, Rockville, MD 20850, USA.

3Protein Potential LLC, Rockville, MD 20850, USA.

4Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA.

5Entomology Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.

6U.S. Military Malaria Vaccine Program, Naval Medical Research Center, Silver Spring, MD 20910, USA.

7Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892, USA.

8Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

9Howard Hughes Medical Institute, Baltimore, MD 21201, USA.

↵†Corresponding author. E-mail: rseder@mail.nih.gov

↵* These authors contributed equally to this work.

↵‡ These authors contributed equally to this work.

Abstract below and at http://www.sciencemag.org/content/early/2013/08/07/science.1241800; full text is available to journal subscribers.

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 well-tolerated when administered 4 to 6 times intravenously (IV) to 40 adults. 0/6 subjects receiving 5 doses, 3/9 subjects receiving 4 doses of 1.35 x 105 PfSPZ vaccine, and 5/6 nonvaccinated controls developed malaria following controlled human malaria infection (P = 0.015 in the 5-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 by IV administration of a vaccine that is safe and meets regulatory standards.

↵§ The VRC 312 Study Team members are listed in the supplementary materials.

Received for publication 11 June 2013.

Accepted for publication 25 July 2013.