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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