Adenovirus vectors as HIV-1 vaccines: where are we? What next?

MP D'Souza, OO Yang - AIDS, 2015 - journals.lww.com
MP D'Souza, OO Yang
AIDS, 2015journals.lww.com
Although antibody studies have moved to the forefront of HIV-1 vaccine research since the
RV144 trial [1, 2], it seems likely that complementary CD8 þ T-cell immunity will be
necessary. This is the best defined protective factor in established HIV-1 infection, based on
numerous lines of evidence, including reduced simian immunodeficiency virus (SIV)
containment after depletion of CD8 þ cells in infected macaques [3–5], HIV-1 sequence
evolution predominately in CD8 þ T-cell epitopes [6], class I human leukocyte antigen (HLA …
Although antibody studies have moved to the forefront of HIV-1 vaccine research since the RV144 trial [1, 2], it seems likely that complementary CD8 þ T-cell immunity will be necessary. This is the best defined protective factor in established HIV-1 infection, based on numerous lines of evidence, including reduced simian immunodeficiency virus (SIV) containment after depletion of CD8 þ cells in infected macaques [3–5], HIV-1 sequence evolution predominately in CD8 þ T-cell epitopes [6], class I human leukocyte antigen (HLA-I) locus being the greatest genetic determinant of immune control [7] and temporal correlation of the CD8 þ T-cell response to drop of viremia during acute infection [8, 9]. Although less certain, this arm of immunity may contribute to preventing HIV-1 infection as well. HIV-1-specific CD8 þ T cells can kill infected cells before virion production and sterilize viral cultures in vitro [10, 11], and have been observed in some highly exposed yet uninfected persons such as a cohort of commercial sex workers in Nairobi [12].
Generating HIV-1-specific CD8 þ T-cell responses by vaccination has been challenging. Exogenous proteins have poor access to the HLA-I pathway, thus numerous vectored approaches have been tested [1]. The most potent in humans has been recombinant adenovirus serotype 5 (rAd5), in versions from Merck Research Laboratories (MRK) and the NIH Vaccine Research Center (VRC). Unfortunately, efficacy trials have been
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