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:
DOI of Published Version
Barouch DH, Stephenson KE, Borducchi EN, Smith K, Stanley K, McNally AG, Liu J, Abbink P, Maxfield LF, Seaman MS, Dugast AS, Alter G, Ferguson M, Li W, Earl PL, Moss B, Giorgi EE, Szinger JJ, Eller LA, Billings EA, Rao M, Tovanabutra S, Sanders-Buell E, Weijtens M, Pau MG, Schuitemaker H, Robb ML, Kim JH, Korber BT, Michael NL. Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys. Cell. 2013 Oct 24;155(3):531-9. doi: 10.1016/j.cell.2013.09.061.
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.