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Journal of Virology, May 2007, p. 4654-4663, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02696-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Comparative Seroprevalence and Immunogenicity of Six Rare Serotype Recombinant Adenovirus Vaccine Vectors from Subgroups B and D{triangledown}

Peter Abbink,1 Angelique A. C. Lemckert,2 Bonnie A. Ewald,1 Diana M. Lynch,1 Matthew Denholtz,1 Shirley Smits,2 Lennart Holterman,2 Irma Damen,2 Ronald Vogels,2 Anna R. Thorner,1 Kara L. O'Brien,1 Angela Carville,3 Keith G. Mansfield,3 Jaap Goudsmit,2 Menzo J. E. Havenga,2 and Dan H. Barouch1*

Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215,1 Crucell Holland BV, 2301 CA, Leiden, The Netherlands,2 New England Primate Research Center, Southborough, Massachusetts 017723

Received 6 December 2006/ Accepted 17 February 2007

Recombinant adenovirus serotype 5 (rAd5) vector-based vaccines are currently being developed for both human immunodeficiency virus type 1 and other pathogens. The potential limitations associated with rAd5 vectors, however, have led to the construction of novel rAd vectors derived from rare Ad serotypes. Several rare serotype rAd vectors have already been described, but a detailed comparison of multiple rAd vectors from subgroups B and D has not previously been reported. Such a comparison is critical for selecting optimal rAd vectors for advancement into clinical trials. Here we describe the construction of three novel rAd vector systems from Ad26, Ad48, and Ad50. We report comparative seroprevalence and immunogenicity studies involving rAd11, rAd35, and rAd50 vectors from subgroup B; rAd26, rAd48, and rAd49 vectors from subgroup D; and rAd5 vectors from subgroup C. All six rAd vectors from subgroups B and D exhibited low seroprevalence in a cohort of 200 individuals from sub-Saharan Africa, and they elicited Gag-specific cellular immune responses in mice both with and without preexisting anti-Ad5 immunity. The rAd vectors from subgroup D were also evaluated using rhesus monkeys and were shown to be immunogenic after a single injection. The rAd26 vectors proved the most immunogenic among the rare serotype rAd vectors studied, although all rare serotype rAd vectors were still less potent than rAd5 vectors in the absence of anti-Ad5 immunity. These studies substantially expand the portfolio of rare serotype rAd vectors that may prove useful as vaccine vectors for the developing world.

* Corresponding author. Mailing address: Research East Room 213, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. Phone: (617) 667-4434. Fax: (617) 667-8210. E-mail: dbarouch{at}bidmc.harvard.edu

{triangledown} Published ahead of print on 28 February 2007.

Journal of Virology, May 2007, p. 4654-4663, Vol. 81, No. 9
0022-538X/07/$08.00+0     doi:10.1128/JVI.02696-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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