Improved protection against simian immunodeficiency virus mucosal challenge in macaques primed with a DNA vaccine and boosted with the recombinant modified vaccinia virus Ankara and recombinant Semliki Forest virus

Frédéric Martinon; Patricia Brochard; Maryline Ripaux; Benoît Delache; Gwenaelle Aurégan; Bruno Vaslin; Roger Le Grand

doi:10.1016/j.vaccine.2007.11.025

Improved protection against simian immunodeficiency virus mucosal challenge in macaques primed with a DNA vaccine and boosted with the recombinant modified vaccinia virus Ankara and recombinant Semliki Forest virus

Vaccine. 2008 Jan 24;26(4):532-45. doi: 10.1016/j.vaccine.2007.11.025. Epub 2007 Dec 3.

Authors

Frédéric Martinon¹, Patricia Brochard, Maryline Ripaux, Benoît Delache, Gwenaelle Aurégan, Bruno Vaslin, Roger Le Grand

Affiliation

¹ CEA, Service d'Immuno-Virologie, DSV, iMETI, 18 route du Panorama, Fontenay Aux Roses, France. frederic.martinon@cea.fr

PMID: 18093703
DOI: 10.1016/j.vaccine.2007.11.025

Abstract

Using the experimental infection of cynomolgus macaques with simian immunodeficiency virus (SIV) as a model of human immunodeficiency virus infection in humans, we studied the immunogenicity and protective efficacy of a vaccine strategy combining DNA, the modified recombinant vaccinia virus strain Ankara (MVA) and Semliki Forest virus (SFV) expressing gag, pol, env, tat, rev and nef from SIV. Although this immunization strategy induced moderate immune responses, the control of pathogenic SIVmac251 infection following mucosal challenge was clearly improved by vaccination. The viral load in vaccinated animals was reduced by 2 logs during the acute phase of infection and, in five of the six macaques, viral load fell below the detection limit at set point. No correlates of immune protection were identified, but SIV-specific T-cell responses were detected earlier in vaccinated animals than in controls. These results highlight the power of live attenuated virus vectors for vaccination strategies.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Genes, Viral
Genetic Vectors / immunology
Immunization, Secondary
Injections, Intramuscular
Injections, Subcutaneous
Lymphocyte Activation
Macaca fascicularis
Male
Mucous Membrane
SAIDS Vaccines / administration & dosage
SAIDS Vaccines / immunology
Semliki forest virus / genetics*
Semliki forest virus / immunology*
Simian Acquired Immunodeficiency Syndrome / immunology
Simian Acquired Immunodeficiency Syndrome / prevention & control*
Simian Acquired Immunodeficiency Syndrome / virology
Simian Immunodeficiency Virus / genetics*
Simian Immunodeficiency Virus / immunology*
T-Lymphocytes / immunology
Vaccines, DNA / administration & dosage*
Vaccines, DNA / immunology
Vaccines, Synthetic / administration & dosage
Vaccines, Synthetic / immunology
Vaccinia virus / genetics
Vaccinia virus / immunology
Viral Load
Viral Vaccines / administration & dosage*
Viral Vaccines / immunology

Substances

SAIDS Vaccines
Vaccines, DNA
Vaccines, Synthetic
Viral Vaccines