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Infection and Immunity, May 2007, p. 2283-2290, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01879-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Priming with an Adenovirus 35-Circumsporozoite Protein (CS) Vaccine followed by RTS,S/AS01B Boosting Significantly Improves Immunogenicity to Plasmodium falciparum CS Compared to That with Either Malaria Vaccine Alone{triangledown}

V. Ann Stewart,1* Shannon M. McGrath,1 Patrice M. Dubois,2,{dagger} Maria G. Pau,3 Pascal Mettens,2 Joseph Shott,1 Michelle Cobb,1 J. Robert Burge,4 David Larson,1 Lisa A. Ware,1 Marie-Ange Demoitie,2 Gerrit Jan Weverling,3 Babak Bayat,2 Jerome H. H. V. Custers,3 Marie-Claude Dubois,2 Joe Cohen,2 Jaap Goudsmit,3 and D. Gray Heppner Jr.1

Division of Malaria Vaccine Development,1 Division of Biometrics, Walter Reed Army Institute of Research, Silver Spring, Maryland,4 GlaxoSmithKline Biologicals, Rixensart, Belgium,2 Crucell Holland BV, Leiden, The Netherlands3

Received 28 November 2006/ Returned for modification 5 January 2007/ Accepted 10 February 2007

The RTS,S/AS02A protein-based vaccine consistently demonstrates significant protection against infection with Plasmodium falciparum malaria and also against clinical malaria and severe disease in children in areas of endemicity. Here we demonstrate with rhesus macaques that priming with a replication-defective human adenovirus serotype 35 (Ad35) vector encoding circumsporozoite protein (CS) (Ad35.CS), followed by boosting with RTS,S in an improved MPL- and QS21-based adjuvant formulation, AS01B, maintains antibody responses and dramatically increases levels of T cells producing gamma interferon and other Th1 cytokines in response to CS peptides. The increased T-cell responses induced by the combination of Ad35.CS and RTS,S/AS01B are sustained for at least 6 months postvaccination and may translate to improved and more durable protection against P. falciparum infection in humans.

* Corresponding author. Mailing address: Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD. Phone: (301) 319-9809. Fax: (301) 319-7358. E-mail: Ann.stewart{at}na.amedd.army.mil

{triangledown} Published ahead of print on 16 February 2007.

Editor: W. A. Petri, Jr.

{dagger} Present address: ImmunoVacc Consulting, Uccle, Belgium.

Infection and Immunity, May 2007, p. 2283-2290, Vol. 75, No. 5
0019-9567/07/$08.00+0     doi:10.1128/IAI.01879-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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