Cell Reports (Mar 2023)
Neonatal SHIV infection in rhesus macaques elicited heterologous HIV-1-neutralizing antibodies
- Bhavna Hora,
- Hui Li,
- Xiaoying Shen,
- Mitchell Martin,
- Yue Chen,
- Madison Berry,
- Tyler Evangelous,
- Andrew N. Macintyre,
- Aria Arus-Altuz,
- Shuyi Wang,
- Ajay Singh,
- Chengyan Zhao,
- Nicole De Naeyer,
- Todd DeMarco,
- Cindy Kuykendall,
- Thaddeus Gurley,
- Kevin O. Saunders,
- Thomas Denny,
- M. Anthony Moody,
- John Misamore,
- Mark G. Lewis,
- Kevin Wiehe,
- Derek W. Cain,
- David C. Montefiori,
- George M. Shaw,
- Wilton B. Williams
Affiliations
- Bhavna Hora
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Hui Li
- Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Xiaoying Shen
- Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA
- Mitchell Martin
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Yue Chen
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Madison Berry
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Tyler Evangelous
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Andrew N. Macintyre
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
- Aria Arus-Altuz
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Shuyi Wang
- Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Ajay Singh
- Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Chengyan Zhao
- Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Nicole De Naeyer
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Todd DeMarco
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Cindy Kuykendall
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Thaddeus Gurley
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Kevin O. Saunders
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA
- Thomas Denny
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
- M. Anthony Moody
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA
- John Misamore
- BIOQUAL, Inc., Rockville, MD 20850, USA
- Mark G. Lewis
- BIOQUAL, Inc., Rockville, MD 20850, USA
- Kevin Wiehe
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
- Derek W. Cain
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA
- David C. Montefiori
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA
- George M. Shaw
- Departments of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
- Wilton B. Williams
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 3
p. 112255
Abstract
Summary: Infants and children infected with human immunodeficiency virus (HIV)-1 have been shown to develop neutralizing antibodies (nAbs) against heterologous HIV-1 strains, characteristic of broadly nAbs (bnAbs). Thus, having a neonatal model for the induction of heterologous HIV-1 nAbs may provide insights into the mechanisms of neonatal bnAb development. Here, we describe a neonatal model for heterologous HIV-1 nAb induction in pathogenic simian-HIV (SHIV)-infected rhesus macaques (RMs). Viral envelope (env) evolution showed mutations at multiple sites, including nAb epitopes. All 13 RMs generated plasma autologous HIV-1 nAbs. However, 8/13 (62%) RMs generated heterologous HIV-1 nAbs with increasing potency over time, albeit with limited breadth, and mapped to multiple nAb epitopes, suggestive of a polyclonal response. Moreover, plasma heterologous HIV-1 nAb development was associated with antigen-specific, lymph-node-derived germinal center activity. We define a neonatal model for heterologous HIV-1 nAb induction that may inform future pediatric HIV-1 vaccines for bnAb induction in infants and children.
