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Journal of Virology, November 2009, p. 10963-10974, Vol. 83, No. 21
0022-538X/09/$08.00+0 doi:10.1128/JVI.01284-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Lentiviral Vector-Based Prime/Boost Vaccination against AIDS: Pilot Study Shows Protection against Simian Immunodeficiency Virus SIVmac251 Challenge in Macaques 
Anne-Sophie Beignon,1
Karine Mollier,2
Christelle Liard,1,
Frédéric Coutant,1
Sandie Munier,1,
Julie Rivière,3
Philippe Souque,1 and
Pierre Charneau1*
CNRS URA 3015, Virologie Moléculaire et Vectorologie, Institut Pasteur,1 TheraVectys, Institut Pasteur-BioTop,2 INSERM U768, Université René Descartes-Paris 5, Hôpital Necker-Enfants Malades, Paris, France3
Received 23 June 2009/ Accepted 5 August 2009
AIDS vaccination has a pressing need for more potent vaccination vectors capable of eliciting strong, diversified, and long-lasting cellular immune responses against human immunodeficiency virus (HIV). Lentiviral vectors have demonstrated efficiency not only as gene delivery vehicles for gene therapy applications but also as vaccination tools. This is likely due to their ability to transduce nondividing cells, including dendritic cells, enabling sustained endogenous antigen presentation and thus the induction of high proportions of specific cytotoxic T cells and long-lasting memory T cells. We show in a first proof-of-concept pilot study that a prime/boost vaccination strategy using lentiviral vectors pseudotyped with a glycoprotein G from two non-cross-reactive vesicular stomatitis virus serotypes elicited robust and broad cellular immune responses against the vector-encoded antigen, simian immunodeficiency virus (SIV) GAG, in cynomolgus macaques. Vaccination conferred strong protection against a massive intrarectal challenge with SIVmac251, as evidenced both by the reduction of viremia at the peak of acute infection (a mean of over 2 log10 fold reduction) and by the full preservation of the CD28+ CD95+ memory CD4+ T cells during the acute phase, a strong correlate of protection against pathogenesis. Although vaccinees continued to display lower viremia than control macaques during the early chronic phase, these differences were not statistically significant by day 50 postchallenge. A not-optimized SIV GAG antigen was chosen to show the strong potential of the lentiviral vector system for vaccination. Given that a stronger protection can be anticipated from a modern HIV-1 antigen design, gene transfer vectors derived from HIV-1 appear as promising candidates for vaccination against HIV-1 infection.
* Corresponding author. Mailing address: Virologie Moléculaire et Vectorologie, Institut Pasteur, 28, Rue du Docteur Roux, 75724 Paris, France. Phone: 33 1 45 68 88 22. Fax: 33 1 40 61 34 65. E-mail: pierre.charneau{at}pasteur.fr
Published ahead of print on 12 August 2009.
Present address: INSERM UMR-S 945/Université Paris 6 UPMC, Paris, France.
Present address: Université Paris Diderot/Paris 7 Unité de Génétique Moléculaire des Virus à ARN, Institut Pasteur, Paris, France.
Journal of Virology, November 2009, p. 10963-10974, Vol. 83, No. 21
0022-538X/09/$08.00+0 doi:10.1128/JVI.01284-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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