An Overview of Human Anti-HIV-1 Neutralizing Antibodies against Diverse Epitopes of HIV-1

Abstract

In this Review, we have addressed some recent developments in the discovery and applications of anti-human immunodeficiency virus type− 1 (HIV−1) broadly neutralizing antibodies (bnAbs) isolated from infected adults and children. The recent developments in human antibody isolation technologies have led to the discovery of several highly potent anti-HIV-1 bnAbs. Herein, we have discussed the characteristics of recently identified bnAbs directed at distinct epitopes of HIV-1, in addition to the existing antibodies, from adults and children and have shed light on the benefits of multispecific HIV-1 bnAbs and their role in the design of polyvalent vaccines.

Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody

“…Structural analysis revealed that the CDRH3 loop of neutralizing antibody 44m stretched deep inside the groove between the N295 and N332 residues, thus reaching the base of the V3 loop of gp120 and established a range of chemical bonds with the nearby favorable amino acids ( Figure 4 A). The total occupied surface area of 44m is ∼750 Å, 2 with extensive participation of the heavy chain. This surface area includes all the CDR regions and FR3 region, but the CDRH1 and CDRH3 loop show a predomination contribution.…”

“…During HIV-1 infection, neutralizing antibodies (nAbs) are elicited against the envelope (env) glycoprotein gp160. 1 , 2 , 3 Highly potent broadly neutralizing antibodies (bnAbs) are found to develop and evolve in only top 1% of HIV-1 infected individuals, classified as elite-neutralizers. 4 , 5 So far, seven distinct epitopes of HIV-1 bnAbs have been identified to be present on the viral env that are: V2-apex, V3-glycan N332-supersite, CD4 binding site (CD4bs), silent-face center (SFC), membrane-proximal external region (MPER), gp120-gp41 interface, and fusion peptide (FP).…”

Diverse competitor B cell responses to a germline-targeting priming immunogen in human Ig loci transgenic mice

“…It was previously shown that the targeted VRC01-class BCRs are approximately 300 to 900-fold less frequent in this mouse model than in humans 35 , therefore making this model less suitable to test the induction of VRC01-class B cells. In addition, long HCDR3s, which are a requirement for several HIV bnAb classes 52 , have been shown to be less comon in Kymice than in humans 49 , thus complicating testing of bnAb induction in these animals. However, despite differences in the frequencies of specific lineages, the overall BCR repertoire in Kymice mice is comparable to humans 48,49 , therefore making this system suitable to investigate “off-target” B cells.…”

A novel bispecific antibody dual-targeting approach for enhanced neutralization against fast-evolving SARS-CoV-2 variants

“…Similar parallels have been observed in HIV-1 studies, where the gp41 FP, a surface-exposed region, has been identified as a target for neutralizing mAbs ( 38 ). However, past attempts to develop HIV-1 FP-targeting mAbs have encountered challenges, primarily due to their relatively low neutralizing potency ( 39 , 40 ). Similarly, studies investigating the SARS-CoV-2 FP-specific mAb, COV44-79, and our own study with K107.1 showed relatively lower or no statistically significant in vitro neutralizing potency against the wild-type and variants because the majority of circulating SARS-CoV-2 does not expose their FP regions, which reside in the S2 domain of the spike proteins ( 17 ).…”