Fig. 8: HIV-1 Env Evolution Signature Analysis in Neonatal and Adult SHIV Infection.

A List of 12 total SHIV-infected neonate RMs that generated plasma heterologous HIV-1 NAbs following SHIV CH848 10.17 DT.E169K infection as previously described²⁹. Among the 12 RMs, eight had increasing plasma NAb titers against one or more heterologous HIV-1 strains as indicated. For the current study, we defined HIV-1 neutralization breadth (low-to-moderate) as neutralization of 30% or more viruses from the virus panel tested at month 18 (M18). Four RMs that developed HIV-1 neutralization breadth are indicated in red font. B LASSIE selected variability env sites that were shared across 3 or more animals (V = variable), ordered by most shared (top) to least. A site was defined to be variable if the LASSIE algorithm detected a loss of 50% or more of the corresponding CH8481017.DT.E169K residue at any given time point. Each column represents an animal, and animals that developed HIV-1 neutralization breadth are highlighted in yellow. Among all sites, 5 were significantly associated with breadth by Fisher exact test (shown in red box). C Logo plots at the 5 sites significantly associated with HIV-1 neutralization breadth comparing animals that developed breadth (left) to those that did not (right). Residues of challenge virus CH8481017.DT.E169K at those positions are shown at the top. Residues more prevalent in one group but not the other are color coded; red, enriched in the breadth group; blue, the non-breadth group. D, E Logo plots at the 5 sites significantly associated with HIV-1 neutralization breadth comparing the neonate (top) to the paired dam (bottom). Residues are color coded red/blue according to whether they are found to be enriched in the HIV-1 neutralization breadth or no-breadth groups, respectively. In panel (D), we studied neonate V058 that developed breadth and by month 18 was able to neutralize 4/8 viruses, while the paired adult dam BD62 did not develop breadth (ID50 threshold of >60). In panel (E), we studied neonate V093 and paired adult dam V060 which both developed HIV-1 neutralization breadth by month 18 and 16, respectively, at the timepoints where we performed Env sequencing analysis. C–E Source data are provided as a Source Data file.