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Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges1,2,3. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIVSME543 Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection4,5 against repetitive, intrarectal SIVMAC251 challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.

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Change history

  • 01 February 2012

    Author initials for E.A.B. were corrected.


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We thank M. Pensiero, A. Fauci, E. Borducchi, S. Clark, R. Hamel, S. King, P. Kozlowski, A. La Porte, G. Landucci, A. Oza, J. Perry, L. Peter, A. Riggs, G. Shaw, N. Simmons, K. Smith, K. Stanley, F. Stephens, Y.-H. Sun, G. Weverling and E. Zablowsky for advice, assistance and reagents. We thank L. Picker, G. Silvestri and B. Walker for critically reviewing this manuscript. The SIVMAC239 peptide pools were obtained from the NIH AIDS Research and Reference Reagent Program. We acknowledge support from the US Military Research and Material Command and the US Military HIV Research Program (W81XWH-07-2-0067); the Ragon Institute of MGH, MIT and Harvard; the National Institutes of Health (AI066924, AI078526, AI084794, AI095985, AI060354, AI002642, RR000168); and the Bill and Melinda Gates Foundation. The opinions in this manuscript are those of the authors and do not reflect the views of the US Department of Defense.

Author information

Author notes

    • Jaap Goudsmit
    •  & Nelson L. Michael

    These authors contributed equally to this work.


  1. Division of Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA

    • Dan H. Barouch
    • , Jinyan Liu
    • , Hualin Li
    • , Lori F. Maxfield
    • , Peter Abbink
    • , Diana M. Lynch
    • , M. Justin Iampietro
    • , Adam SanMiguel
    •  & Michael S. Seaman
  2. Ragon Institute of MGH, MIT, and Harvard, Boston, Massachusetts 02114, USA

    • Dan H. Barouch
  3. Duke University Medical Center, Durham, North Carolina 27710, USA

    • Guido Ferrari
  4. University of California Irvine School of Medicine, Irvine, Californian 92697, USA

    • Donald N. Forthal
  5. National Institute of Allergy and Infectious Diseases, Bethesda, Massachusetts 20892, USA

    • Ilnour Ourmanov
    •  & Vanessa M. Hirsch
  6. New England Primate Research Center, Southborough, Massachusetts 01772, USA

    • Angela Carville
    •  & Keith G. Mansfield
  7. EMMES Corporation, Rockville, Maryland 20850, USA

    • Donald Stablein
  8. Crucell Holland BV, 2301 CA, Leiden, The Netherlands

    • Maria G. Pau
    • , Hanneke Schuitemaker
    • , Jerald C. Sadoff
    •  & Jaap Goudsmit
  9. US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA

    • Erik A. Billings
    • , Mangala Rao
    • , Merlin L. Robb
    • , Jerome H. Kim
    • , Mary A. Marovich
    •  & Nelson L. Michael


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D.H.B., M.G.P., H.S., J.C.S., J.G., M.L.R., J.H.K., M.A.M. and N.L.M. designed the study and analysed data. J.L., H.L., D.M.L., M.J.I. and A.S. performed the cellular immunogenicity assays. H.L., M.J.I., M.S.S., G.F., D.N.F., E.A.B. and M.R. performed the humoral immunogenicity assays. L.F.M., P.A., I.O. and V.M.H. prepared the vaccine constructs. A.C. and K.G.M. led the clinical care of the rhesus monkeys. D.S. led the statistical analyses. D.H.B. led the study and wrote the paper with all co-authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Dan H. Barouch.

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