EBioMedicine (Oct 2016)
Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity
- Todd Bradley,
- Ashley Trama,
- Nancy Tumba,
- Elin Gray,
- Xiaozhi Lu,
- Navid Madani,
- Fatemeh Jahanbakhsh,
- Amanda Eaton,
- Shi-Mao Xia,
- Robert Parks,
- Krissey E. Lloyd,
- Laura L. Sutherland,
- Richard M. Scearce,
- Cindy M. Bowman,
- Susan Barnett,
- Salim S. Abdool-Karim,
- Scott D. Boyd,
- Bruno Melillo,
- Amos B. Smith III,
- Joseph Sodroski,
- Thomas B. Kepler,
- S.Munir Alam,
- Feng Gao,
- Mattia Bonsignori,
- Hua-Xin Liao,
- M. Anthony Moody,
- David Montefiori,
- Sampa Santra,
- Lynn Morris,
- Barton F. Haynes
Affiliations
- Todd Bradley
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Ashley Trama
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Nancy Tumba
- National Institute for Communicable Diseases, Johannesburg 2131, South Africa
- Elin Gray
- National Institute for Communicable Diseases, Johannesburg 2131, South Africa
- Xiaozhi Lu
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Navid Madani
- Dana-Farber Cancer Institute, Boston, MA 02215, USA
- Fatemeh Jahanbakhsh
- Dana-Farber Cancer Institute, Boston, MA 02215, USA
- Amanda Eaton
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Shi-Mao Xia
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Robert Parks
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Krissey E. Lloyd
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Laura L. Sutherland
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Richard M. Scearce
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Cindy M. Bowman
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Susan Barnett
- Novartis Vaccines and Diagnostics, Inc., Cambridge, MA, USA
- Salim S. Abdool-Karim
- Center for AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban 4013, South Africa
- Scott D. Boyd
- Stanford University, Palo Alto, CA 94305, USA
- Bruno Melillo
- University of Pennsylvania, Philadelphia, PA 19104, USA
- Amos B. Smith III
- University of Pennsylvania, Philadelphia, PA 19104, USA
- Joseph Sodroski
- Dana-Farber Cancer Institute, Boston, MA 02215, USA
- Thomas B. Kepler
- Boston University, Boston, MA 02118, USA
- S.Munir Alam
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Feng Gao
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Mattia Bonsignori
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Hua-Xin Liao
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- M. Anthony Moody
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- David Montefiori
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- Sampa Santra
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
- Lynn Morris
- National Institute for Communicable Diseases, Johannesburg 2131, South Africa
- Barton F. Haynes
- Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
- DOI
- https://doi.org/10.1016/j.ebiom.2016.08.045
- Journal volume & issue
-
Vol. 12,
no. C
pp. 196 – 207
Abstract
Most HIV-1 vaccines elicit neutralizing antibodies that are active against highly sensitive (tier-1) viruses or rare cases of vaccine-matched neutralization-resistant (tier-2) viruses, but no vaccine has induced antibodies that can broadly neutralize heterologous tier-2 viruses. In this study, we isolated antibodies from an HIV-1-infected individual that targeted the gp41 membrane-proximal external region (MPER) that may have selected single-residue changes in viral variants in the MPER that resulted in neutralization sensitivity to antibodies targeting distal epitopes on the HIV-1 Env. Similarly, a single change in the MPER in a second virus from another infected-individual also conferred enhanced neutralization sensitivity. These gp41 single-residue changes thus transformed tier-2 viruses into tier-1 viruses that were sensitive to vaccine-elicited tier-1 neutralizing antibodies. These data demonstrate that Env amino acid changes within the MPER bnAb epitope of naturally-selected escape viruses can increase neutralization sensitivity to multiple types of neutralizing antibodies, and underscore the critical importance of the MPER for maintaining the integrity of the tier-2 HIV-1 trimer.
