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Journal of Virology, June 2005, p. 7135-7145, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7135-7145.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Characterization of Human Immunodeficiency Virus Gag-Specific Gamma Interferon-Expressing Cells following Protective Mucosal Immunization with Alphavirus Replicon Particles

Soumi Gupta,1 Ramesh Janani,2 Qian Bin,1 Paul Luciw,1 Catherine Greer,2 Silvia Perri,2 Harold Legg,2 John Donnelly,2 Susan Barnett,2 Derek O'Hagan,2 John M. Polo,2 and Michael Vajdy2*

Department of Pathology and Center for Comparative Medicine, University of California, Davis,1 Chiron Vaccines, 4560 Horton Street, Emeryville, California2

Received 10 November 2004/ Accepted 23 January 2005

A safe, replication-defective viral vector that can induce mucosal and systemic immune responses and confer protection against many infectious pathogens, such as human immunodeficiency virus type 1 (HIV-1), may be an ideal vaccine platform. Accordingly, we have generated and tested alphavirus replicon particles encoding HIV-1 Gag from Sindbis virus (SIN-Gag) and Venezuelan equine encephalitis virus (VEE-Gag), as well as chimeras between the two (VEE/SIN-Gag). Following intramuscular (i.m.), intranasal (i.n.), or intravaginal (IVAG) immunization with VEE/SIN-Gag and an IVAG challenge with vaccinia virus encoding HIV Gag (VV-Gag), a larger number of Gag-specific CD8+ intracellular gamma interferon-expressing cells (iIFNEC) were detected in iliac lymph nodes (ILN), which drain the vaginal/uterine mucosa (VUM), than were observed after immunizations with SIN-Gag. Moreover, a single i.n. or IVAG immunization with VEE/SIN-Gag induced a larger number of cells expressing HIV Gag in ILN, and immunizations with VEE/SIN-Gag through any route induced better protective responses than immunizations with SIN-Gag. In VUM, a larger percentage of iIFNEC expressed {alpha}4ß7 or {alpha}Eß7 integrin than expressed CD62L integrin. However, in spleens (SP), a larger percentage of iIFNEC expressed {alpha}4ß7 or CD62L than expressed {alpha}Eß7. Moreover, a larger percentage of iIFNEC expressed the chemokine receptor CCR5 in VUM and ILN than in SP. These results demonstrate a better induction of cellular and protective responses following immunizations with VEE/SIN-Gag than that following immunizations with SIN-Gag and also indicate a differential expression of homing and chemokine receptors on iIFNEC in mucosal effector and inductive sites versus systemic lymphoid tissues.

* Corresponding author. Mailing address: Chiron Vaccines, 4560 Horton Street, M/S 4.3, Emeryville, CA 94608. Phone: (510) 923-8595. Fax: (510) 923-2586. E-mail: michael_vajdy{at}chiron.com.

Journal of Virology, June 2005, p. 7135-7145, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7135-7145.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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