Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus

By H. Liao, R. Lynch, T. Zhou, Feng Gao, S. Alam, S. Boyd, A. Fire, K. M. Roskin, Chaim A. Schramm, Zhenhai Zhang and 34 more. Nature, 2013

1,030 citations recorded by the source corpus.

Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.

Subfields: Immunology, Radiology, Nuclear Medicine and Imaging, Virology

View Paper: https://www.semanticscholar.org/paper/e913900d9edc5c2ebcd857d41468e1f294665355

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In Radiology, Nuclear Medicine and Imaging

Citations in the corpus

OptMAVEn – A New Framework for the de novo Design of Antibody Variable Region Models Targeting Specific Antigen Epitopes (2014, background): “[29], superhumanization [30], framework shuffling [31] and guided selection [32] have produced antibodies more homologous to human sequences, often but not always leading to reductions in immunogenicity to clinically acceptable levels [33].”
GERMINAL CENTER B CELL DYNAMICS (2016, positive): “…extensively selected) bNAbs often arise from very low-affinity precursors, exemplify how little is known regarding the pace and stringency of GC selection, especially during long-lived responses (Klein et al., 2013; Liao et al., 2013; Lingwood et al., 2012; Pappas et al., 2014; Tan et al., 2016).”
Human Circulating PD-1+CXCR3−CXCR5+ Memory Tfh Cells Are Highly Functional and Correlate with Broadly Neutralizing HIV Antibody Responses (2013, positive): “It is likely that antigen load and a recursive process of antibody mutation and virus escape (Richman et al., 2003) provide the basis for the process of antibody epitope honing to the most conserved HIV envelope epitopes (Liao et al., 2013).”
Developmental Pathway of the MPER-Directed HIV-1-Neutralizing Antibody 10E8 (2016, background): “Thus far, this has been accomplished for three antibody lineages: the CD4-binding-site-directed CH103 lineage from donor CH505 [5], a second CD4-binding site-directed lineage, CH235, from the same donor [6] and the V1V2-directed VRC26 lineage from donor CAP256 [7].”
RosettaAntibodyDesign (RAbD): A general framework for computational antibody design (2017, methodology): “The starting antibody complex was obtained from the Protein Data Bank with ID 4JAN [82], renumbered using PyIgClassify, and minimized into the Rosetta energy function as described above.”
Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1 (2014, background): “However, whether or not HCAb can more easily be elicited than IgG does not alter one similarity between neutralizing antibodies derived from HIV-positive patients and J3, namely that their unmutated ancestors do not bind HIV Env [46,47,48], except when modified to do exactly that [49,50,51] or in on”