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Clinical and Vaccine Immunology, June 2007, p. 748-755, Vol. 14, No. 6
1071-412X/07/$08.00+0     doi:10.1128/CVI.00037-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cellular and Humoral Immune Responses to Alphavirus Replicon Vaccines Expressing Cytomegalovirus pp65, IE1, and gB Proteins{triangledown} ,{dagger}

Elizabeth A. Reap,* Sergey A. Dryga,{ddagger} John Morris, Bryan Rivers, Pamela K. Norberg, Robert A. Olmsted, and Jeffrey D. Chulay

AlphaVax, Inc., Research Triangle Park, North Carolina

Received 17 January 2007/ Returned for modification 7 March 2007/ Accepted 10 April 2007

Development of vaccines against cytomegalovirus (CMV) is an important public health priority. We used a propagation-defective, single-cycle RNA replicon vector system derived from an attenuated strain of an alphavirus, Venezuelan equine encephalitis virus, to produce virus-like replicon particles (VRP) expressing various combinations of pp65, IE1, or gB proteins of human CMV. Protein expression in VRP-infected cells was highest with single-promoter replicons expressing pp65, IE1, a pp65/IE1 fusion protein, or the extracellular domain of gB and with double-promoter replicons expressing pp65 and IE1. Protein expression was lower with double- and triple-promoter replicons expressing gB, especially the full-length form of gB. BALB/c mice immunized with VRP expressing gB developed high titers of neutralizing antibody to CMV, and mice immunized with VRP expressing pp65, IE1, or a pp65/IE1 fusion protein developed robust antigen-specific T-cell responses as measured by gamma interferon enzyme-linked immunospot assay. Three overlapping immunodominant pp65 peptides contained a nine-amino-acid sequence (LGPISGHVL) that matches the consensus binding motif for a major histocompatibility complex H2-Dd T-cell epitope. These data provide the basis for further development and clinical evaluation of an alphavirus replicon vaccine for CMV expressing the pp65, IE1, and gB proteins.

* Corresponding author. Mailing address: AlphaVax, Inc., 2 Triangle Drive, P.O. Box 110307, Research Triangle Park, NC 27709-0307. Phone: (919) 595-0326. Fax: (919) 595-0401. E-mail: reap{at}alphavax.com

{triangledown} Published ahead of print on 18 April 2007.

{dagger} Supplemental material for this article may be found at http://cvi.asm.org/.

{ddagger} Present address: Seracare LifeSciences, Inc., Gaithersburg, MD 20877.

Clinical and Vaccine Immunology, June 2007, p. 748-755, Vol. 14, No. 6
1071-412X/07/$08.00+0     doi:10.1128/CVI.00037-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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