The attenuated vaccine against yellow fever (YFV) is extremely efficacious and has been used by more than 400 million people over the past 70 years. Because of its impressive track record, researchers are now investigating whether YFV can be modified to work against other diseases, including Japanese encephalitis, dengue, West Nile virus and malaria. The latest addition to this list is HIV; in a new study published recently by the Journal of Virology, Myrna C. Bonaldo and colleagues report preliminary data showing that YFV can be modified to encode the Gag protein from SIV and is a potent inducer of T cell immune responses in macaques. The levels of SIV-specific CD8 T cells induced by the YFV/SIV construct were equivalent to those induced live-attenuated SIV vaccines (the most successful vaccines studied to date in the macaque model). Challenge studies have not yet been conducted but the researchers suggest YFV is an excellent candidate for further development as an HIV vaccine vector.
JVI Accepts, published online ahead of print on 20 January 2010
J. Virol. doi:10.1128/JVI.02255-09
Myrna C. Bonaldo, Mauricio A. Martins, Richard Rudersdorf, Philip A. Mudd, Jonah B. Sacha, Shari M. Piaskowski, Patrícia C. Costa Neves, Marlon G. Veloso de Santana, Lara Vojnov, Saverio Capuano III, Eva G. Rakasz, Nancy A. Wilson, John Fulkerson, Jerald C. Sadoff, David I. Watkins, and Ricardo Galler
Laboratorio de Biologia Molecular de Flavivírus, Instituto Oswaldo Cruz – FIOCRUZ, Rio de Janeiro, Brazil; Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin; Aeras Global TB Vaccine Foundation, Rockville, MD; Instituto de Tecnologia em Imunobiologicos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
Abstract
Here we describe a novel vaccine vector for expressing HIV antigens. We show that recombinant attenuated yellow fever vaccine virus 17D expressing SIVmac239 Gag sequences can be used as a vector to generate SIV-specific CD8+ T cell responses in the rhesus macaque. Priming with recombinant BCG expressing SIV antigens increased the frequency of these SIV-specific CD8+ T cell responses after recombinant YF17D boosting. These recombinant YF17D-induced SIV-specific CD8+ T cells secreted several cytokines, were largely effector memory and suppressed viral replication in CD4+ T cells.
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