Open Access Study protocol

SIV escape mutants in rhesus macaques vaccinated with NEF-derived lipopeptides and challenged with pathogenic SIVmac251

Pascale Villefroy1,2,3,4†, Franck Letourneur1,2,3,4†, Zoe Coutsinos1,2,3,4, Lorenzo Mortara1,14,2,3,4, Christian Beyer5,6,7, Helene Gras-Masse10,11,8,9, Jean-Gerard Guillet1,2,3,4 and Isabelle Bourgault-Villada1,12,13,2,3,4*

Author Affiliations

1 Institut Cochin, Département d'Immunologie, Hôpital Cochin, 27, rue du Faubourg Saint-Jacques, Paris, F-75014, France

2 INSERM U567, Paris, F-75014, France

3 CNRS UMR 8104, Paris, F-75014, France

4 Université Paris 5, Faculté de Médecine René Descartes, UM3, F-75014, France

5 Institut de Virologie de la Faculté de Médecine, 3 rue Koeberlé, Strasbourg, F-67000, France

6 INSERM U74, Strasbourg, F-67000, France

7 Université Pasteur de Strasbourg I, Strasbourg, F-67000, France

8 Institut de Biologie de Lille, Laboratoire Synthèse, Structure et Fonction des Biomolécules, 1 rue du Professeur Calmette, BP 447, F-59021 Lille Cedex, France

9 URA CNRS 1309, F-59021 Lille Cedex, France

10 Université de Lille II, F-59021 Lille Cedex, France

11 Institut Pasteur de Lille, F-59021 Lille Cedex, France

12 Assistance Publique-Hôpitaux de Paris, Service de Dermatologie, Hôpital Ambroise Paré, 9 avenue Charles de Gaulle, F-92104 Boulogne, France

13 Université de Versailles Saint Quentin en Yvelines, Versailles Cedex, F-78035, France

14 Department of Clinical and Biological Sciences, School of Medicine, University of Insubria, Varese, Italy

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Virology Journal 2006, 3:65 doi:10.1186/1743-422X-3-65

Published: 31 August 2006

Abstract

Background

Emergence of viral variants that escape CTL control is a major hurdle in HIV vaccination unless such variants affect gene regions that are essential for virus replication. Vaccine-induced multispecific CTL could also be able to control viral variants replication. To explore these possibilities, we extensively characterized CTL responses following vaccination with an epitope-based lipopeptide vaccine and challenge with pathogenic SIVmac251. The viral sequences corresponding to the epitopes present in the vaccine as well as the viral loads were then determined in every macaque following SIV inoculation.

Results

In most cases, the emergence of several viral variants or mutants within vaccine CTL epitopes after SIV challenge resulted in increased viral loads except for a single macaque, which showed a single escape viral variant within its 6 vaccine-induced CTL epitopes.

Conclusion

These findings provide a better understanding of the evolution of CD8+ epitope variations after vaccination-induced CTL expansion and might provide new insight for the development of an effective HIV vaccine.