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Protective Efficacy of a Global HIV-1 Mosaic Vaccine against Heterologous SHIV Challenges in Rhesus Monkeys
Dan H. Barouch,Kathryn E. Stephenson,Erica N. Borducchi,Kaitlin Smith,Kelly Stanley,Anna G. McNally,Jinyan Liu,Peter Abbink,Lori F. Max?eld,Michael S. Seaman,Anne-Sophie Dugast,Galit Alter,Melissa Ferguson,Wenjun Li,Patricia L. Earl,Bernard Moss,Elena E. Giorgi,James J. Szinger,Leigh Anne Eller,7
Erik A. Billings,Mangala Rao,Sodsai Tovanabutra,Eric Sanders-Buell,Mo Weijtens,Maria G. Pau,8
Hanneke Schuitemaker,Merlin L. Robb,Jerome H. Kim,Bette T. Korber,and Nelson L. Michael
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.
