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About the Authors:
Viraj Kulkarni
Affiliation: Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America
Antonio Valentin
Affiliation: Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America
Margherita Rosati
Affiliation: Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America
Morgane Rolland
Current address: United States Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America; The Henry M. Jackson Foundation, Bethesda, Maryland, United States of America
Affiliation: Departments of Microbiology, Medicine and Laboratory Medicine, University of Washington, Seattle, Washington, United States of America
James I. Mullins
Affiliation: Departments of Microbiology, Medicine and Laboratory Medicine, University of Washington, Seattle, Washington, United States of America
George N. Pavlakis
* E-mail: [email protected] (BKF); [email protected] (GNP)
Affiliation: Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America
Barbara K. Felber
* E-mail: [email protected] (BKF); [email protected] (GNP)
Affiliation: Human Retrovirus Pathogenesis Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, United States of America
Introduction
The development of an effective HIV vaccine is critical to control the AIDS pandemic. Protection against HIV is difficult to obtain in part because the virus readily mutates and generates viable alternatives to the epitopes targeted by the immune system of the host. To address the problem of viral variability many strategies have been tested [1]–[19]. We have focused in conserved elements from the HIV-1 proteome and have based our immunogen designs on (a) stringent conservation among all HIV sequences, (b) selection of epitopes associated with better virologic control in HIV-1 infected individuals, and (c) optimizing immunogen expression and proteolytic cleavage [11], [12], [16]–[25]. We focused on Gag as a prototype vaccine, because Gag-specific CD8+ T cell responses were found to correlate with control of viremia in clade B and C infected individuals [26]–[29], to contribute to control HIV-1 after infection in the Step trial [30], and Gag-specific CD4+ T cell responses were associated with virus control [31], [32]. We selected 7 conserved elements (CE) within...