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Journal of Virology, August 2002, p. 7544-7553, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7544-7553.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Enhanced Presentation of Major Histocompatibility Complex Class I-Restricted Human Immunodeficiency Virus Type 1 (HIV-1) Gag-Specific Epitopes after DNA Immunization with Vectors Coding for Vesicular Stomatitis Virus Glycoprotein- Pseudotyped HIV-1 Gag Particles

D. Marsac,¹ D. Loirat,^1,2 C. Petit,³ O. Schwartz,³ and M.-L. Michel^1*

Unité de Recombinaison et Expression Génétique, INSERM U.163,¹ Unité Rétrovirus et Transfert Génétique, Institut Pasteur, 75724 Paris Cedex 15,³ IDM, 75011 Paris, France²

Received 25 January 2002/ Accepted 26 April 2002

In vivo priming of cytotoxic T lymphocytes (CTL) by DNA injection predominantly occurs by antigen transfer from DNA-transfected cells to antigen-presenting cells. A rational strategy for increasing DNA vaccine potency would be to use a delivery system that facilitates antigen uptake by antigen-presenting cells. Exogenous antigen presentation through the major histocompatibility complex (MHC) class I-restricted pathway of some viral antigens is increased after adequate virus-receptor interaction and the fusion of viral and cellular membranes. We used DNA-based immunization with plasmids coding for human immunodeficiency virus type 1 (HIV-1) Gag particles pseudotyped with vesicular stomatitis virus glycoprotein (VSV-G) to generate Gag-specific CTL responses. The presence of the VSV-G-encoding plasmid not only increased the number of mice displaying anti-Gag-specific cytotoxic response but also increased the efficiency of specific lysis. In vitro analysis of processing confirmed that exogenous presentation of Gag epitopes occurred much more efficiently when Gag particles were pseudotyped with the VSV-G envelope. We show that the VSV-G-pseudotyped Gag particles not only entered the MHC class II processing pathway but also entered the MHC class I processing pathway. In contrast, naked Gag particles entered the MHC class II processing pathway only. Thus, the combined use of DNA-based immunization and nonreplicating pseudotyped virus to deliver HIV-1 antigen to the immune system in vivo could be considered in HIV-1 vaccine design.

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* Corresponding author. Mailing address: Unité de Recombinaison et Expression Génétique, INSERM U.163, Institut Pasteur, 28 Rue du Docteur Roux, 75724 Paris Cédex 15, France. Phone: 33/1 45 68 88 49. Fax: 33/1 45 68 89 43. E-mail: maloum{at}pasteur.fr.

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Journal of Virology, August 2002, p. 7544-7553, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7544-7553.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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