Cell Reports (Jan 2016)
Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site
- Todd Bradley,
- Daniela Fera,
- Jinal Bhiman,
- Leila Eslamizar,
- Xiaozhi Lu,
- Kara Anasti,
- Ruijung Zhang,
- Laura L. Sutherland,
- Richard M. Scearce,
- Cindy M. Bowman,
- Christina Stolarchuk,
- Krissey E. Lloyd,
- Robert Parks,
- Amanda Eaton,
- Andrew Foulger,
- Xiaoyan Nie,
- Salim S. Abdool Karim,
- Susan Barnett,
- Garnett Kelsoe,
- Thomas B. Kepler,
- S. Munir Alam,
- David C. Montefiori,
- M. Anthony Moody,
- Hua-Xin Liao,
- Lynn Morris,
- Sampa Santra,
- Stephen C. Harrison,
- Barton F. Haynes
Affiliations
- Todd Bradley
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Daniela Fera
- Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Jinal Bhiman
- National Institute for Communicable Diseases, Johannesburg 2131, South Africa
- Leila Eslamizar
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
- Xiaozhi Lu
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Kara Anasti
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Ruijung Zhang
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Laura L. Sutherland
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Richard M. Scearce
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Cindy M. Bowman
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Christina Stolarchuk
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Krissey E. Lloyd
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Robert Parks
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Amanda Eaton
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Andrew Foulger
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Xiaoyan Nie
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Salim S. Abdool Karim
- Center for AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban 4013, South Africa
- Susan Barnett
- Novartis Vaccines and Diagnostics, Inc., Cambridge, MA 02139, USA
- Garnett Kelsoe
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Thomas B. Kepler
- Boston University, Boston, MA 02118, USA
- S. Munir Alam
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- David C. Montefiori
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- M. Anthony Moody
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Hua-Xin Liao
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Lynn Morris
- National Institute for Communicable Diseases, Johannesburg 2131, South Africa
- Sampa Santra
- Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
- Stephen C. Harrison
- Laboratory of Molecular Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Barton F. Haynes
- Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- DOI
- https://doi.org/10.1016/j.celrep.2015.12.017
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 43 – 54
Abstract
Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.
