Broad-neutralizing antibodies (bNAbs) are identified to effectively neutralize diverse viruses strains. The viral fusion machines responsible for merging virus and target-cell membranes are often targeted, which acts as an essential step in viral entry. In vaccine research, it has been a long-sought goal to induce Abs capable of neutralizing diverse strains of HIV-1. To understand how bNAbs can be elicited, five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) were identified, characterized and tracked in vaccinated macaques over time via GenScript's Peptide Service. Through FP-carrier priming, each of these lineages has been initiated and expanded with envelop (Env)-trimer boosts which induces cross-reactive neutralization. The study also found that two of the five lineages belong to a reproducible class that is capable of neutralizing almost 60% of the total studied diverse viral strains. These Abs had FP-focused binding-energy hotspots, whereas several other FP-directed Abs induced by Env trimer-only immunization were less FP-focused or broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.
