Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding

By J. Scheid, H. Mouquet, B. Ueberheide, Ron Diskin, F. Klein, Thiago Y. Oliveira, J. Pietzsch, David Fenyo, A. Abadir, K. Velinzon and 12 more. Science, 2011

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Anti-HIV broadly neutralizing antibodies with similar specificities and modes of binding were found in multiple HIV-infected individuals. Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.

Subfields: Molecular Biology, Radiology, Nuclear Medicine and Imaging, Virology

View Paper: https://www.semanticscholar.org/paper/085694a80061783fc13a7ea08b0d9533bca172f7

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Citations in the corpus

Human Circulating PD-1+CXCR3−CXCR5+ Memory Tfh Cells Are Highly Functional and Correlate with Broadly Neutralizing HIV Antibody Responses (2013, neutral): “HIV bnAbs that can neutralize 70% or more of globally circulating HIV strains (Huang et al., 2012; Scheid et al., 2011; Walker et al., 2011; 2009) and can prevent infection in passive-transfer experiments using non-human primates (Moldt et al., 2012) have been characterized.”
A Combination of Human Broadly Neutralizing Antibodies against Hepatitis B Virus HBsAg with Distinct Epitopes Suppresses Escape Mutations (2020, background): “The near identity of clones of HBV bNAbs in unrelated individuals is akin to reports for elite responders to HIV-1 (Scheid et al., 2011; West et al., 2012), influenza (Laursen and Wilson, 2013; Pappas et al.”
IDEPI: Rapid Prediction of HIV-1 Antibody Epitopes and Other Phenotypic Features from Sequence Data Using a Flexible Machine Learning Platform (2014, background): “8ANC195 is a broadly neutralizing antibody whose epitope has not been structurally confirmed [65], but it was used as a test case for computational epitope prediction and experimental confirmation by two independent groups [45,46].”
Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens (2017, background): “Mature VRC01-class bnAbs depend on extensive affinity maturation to develop potency and breadth during HIV infection, with 32%–48% mutated amino acids (aa) in most VRC01-class bnAbs (Huang et al., 2016; Scheid et al., 2011).”