Neonatal SHIV infection in rhesus macaques elicited heterologous HIV-1-neutralizing antibodies
oleh: 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
| Format: | Article |
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| Diterbitkan: | Elsevier 2023-03-01 |
Deskripsi
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.