Neonatal Rhesus Macaques Have Distinct Immune Cell Transcriptional Profiles following HIV Envelope Immunization
Qi Han, Todd Bradley, Wilton B. Williams, Derek W. Cain, David C. Montefiori, Kevin O. Saunders, Robert Parks, R. Whitney Edwards, Guido Ferrari, Olaf Mueller, Xiaoying Shen, Kevin Wiehe, Steven G. Reed, Christopher B. Fox, Wes Rountree, Nathan Vandergrift, Yunfei Wang, Laura L. Sutherland, Sampa Santra, M. Anthony Moody, Sallie R. Permar, Georgia D. Tomaras, Mark G. Lewis, Koen K. A. Van Rompay, Barton F. Haynes
Abstract
HIV-1-infected infants develop broadly neutralizing antibodies (bnAbs) more rapidly than adults, suggesting differences in the neonatal versus adult responses to the HIV-1 envelope (Env). Here, trimeric forms of HIV-1 Env immunogens elicit increased gp120- and gp41-specific antibodies more rapidly in neonatal macaques than adult macaques. Transcriptome analyses of neonatal versus adult immune cells after Env vaccination reveal that neonatal macaques have higher levels of the apoptosis regulator BCL2 in T cells and lower levels of the immunosuppressive interleukin-10 (IL-10) receptor alpha (IL10RA) mRNA transcripts in T cells, B cells, natural killer (NK) cells, and monocytes. In addition, immunized neonatal macaques exhibit increased frequencies of activated blood T follicular helper-like (Tfh) cells compared to adults. Thus, neonatal macaques have transcriptome signatures of decreased immunosuppression and apoptosis compared with adult macaques, providing an immune landscape conducive to early-life immunization prior to sexual debut.