Author/Authors :
Dan H. Barouch، نويسنده , , Kathryn E. Stephenson، نويسنده , , Erica N. Borducchi، نويسنده , , Kaitlin Smith، نويسنده , , Kelly Stanley، نويسنده , , Anna G. McNally، نويسنده , , Jinyan Liu، نويسنده , , Peter Abbink، نويسنده , , Lori F. Maxfield، نويسنده , , Michael S. Seaman، نويسنده , , Anne-Sophie Dugast، نويسنده , , Galit Alter، نويسنده , , Melissa Ferguson، نويسنده , , WenJun Li، نويسنده , , Patricia L. Earl، نويسنده , , Bernard Moss، نويسنده , , Elena E. Giorgi، نويسنده , , James J. Szinger، نويسنده , , Leigh Anne Eller، نويسنده , , Erik A. Billings، نويسنده , , et al.، نويسنده ,
Abstract :
The global diversity of HIV-1 represents a critical challenge facing HIV-1 vaccine development. HIV-1 mosaic antigens are bioinformatically optimized immunogens designed for improved coverage of HIV-1 diversity. However, the protective efficacy of such global HIV-1 vaccine antigens has not previously been evaluated. Here, we demonstrate the capacity of bivalent HIV-1 mosaic antigens to protect rhesus monkeys against acquisition of infection following heterologous challenges with the difficult-to-neutralize simian-human immunodeficiency virus SHIV-SF162P3. Adenovirus/poxvirus and adenovirus/adenovirus vector-based vaccines expressing HIV-1 mosaic Env, Gag, and Pol afforded a significant reduction in the per-exposure acquisition risk following repetitive, intrarectal SHIV-SF162P3 challenges. Protection against acquisition of infection correlated with vaccine-elicited binding, neutralizing, and functional nonneutralizing antibodies, suggesting that the coordinated activity of multiple antibody functions may contribute to protection against difficult-to-neutralize viruses. These data demonstrate the protective efficacy of HIV-1 mosaic antigens and suggest a potential strategy for the development of a global HIV-1 vaccine.
