Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys
Department of Medicine, Division of Preventive and Behavioral Medicine
AIDS Vaccines; Animals; Antibody Formation; Female; HIV Antigens; *HIV-1; Human Immunodeficiency Virus Proteins; Immunity, Cellular; Macaca mulatta; Male; Molecular Sequence Data; Specific Pathogen-Free Organisms
Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Virus Diseases
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. PAPERCLIP:
Barouch, Dan H.; Stephenson, Kathryn E.; Borducchi, Erica N.; Smith, Kaitlin; Stanley, Kelly; McNally, Anna G.; Liu, Jinyan; Abbink, Peter; Maxfield, Lori F.; Seaman, Michael S.; and Li, Wenjun, "Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys" (2013). Preventive and Behavioral Medicine Publications and Presentations. 278.