XProtective 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. Maxfield, 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, Erik A. BillingsMangala Rao, Sodsai Tovanabutra, Eric Sanders-Buell, Mo Weijtens, Maria G. Pau, Hanneke Schuitemaker, Merlin L. Robb, Jerome H. Kim, Bette T. Korber, Nelson L. Michael

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

283 Scopus citations

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. PaperClip

Original languageEnglish
Pages (from-to)531
Number of pages1
JournalCell
Volume155
Issue number3
DOIs
StatePublished - 24 Oct 2013
Externally publishedYes

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