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Displaying record number 3398
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MAb ID |
BF520.1 |
HXB2 Location |
Env |
Env Epitope Map
|
Author Location |
Env |
Epitope |
|
Subtype |
A1 |
Ab Type |
gp120 V3 // V3 glycan (V3g) |
Neutralizing |
P (tier 2) View neutralization details |
Species
(Isotype)
|
human |
Patient |
BF520 |
Immunogen |
HIV-1 infection |
Country |
Kenya |
Keywords |
antibody generation, antibody interactions, antibody lineage, antibody polyreactivity, broad neutralizer, computational prediction, effector function, germline, neutralization, responses in children, review, structure |
Notes
Showing 5 of
5 notes.
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BF520.1: This review on Ab response to HIV-1 includes both Fab and Fc functions in bnAbs as well as non-nAbs.(1) Fc effector functions as modulators of the innate and adaptive immune response by Abs were found to associate with lower infection in RV144, but standardized assays are lacking in the field, despite this new Fc effector functions like antibody-dependent cellular phagocytosis (ADCP) have been found with differing kinds of phagocytosis, depending on the phagocytosing cell. (2) Observation of donor-elicited bnAbs is the major source of information on Ab development, including some pediatric donors like that of the BF520.1 Ab lineage that proved that unusual and chronic-response genetic features of bnAbs may not always be necessary for bnAb breadth, since BF520.1 exhibits moderate breadth but lower levels of indels and SHM. (3) BCR sequence analysis is also a method of finding different bnAb VL chains, increasing the repertoire of public Ab and other genes available to generate neutralizing Abs. (4) While most bnAbs are of the IgG1 isotype, a few MPER Abs are IgG3, and IgA may cooperate with IgG functions and ADCC. (5) Superinfection correlates with breadth of response due to distinct B-cell lineages being stimulated, and this is an additive rather than synergistic effect (6) Finally, the infecting virus, including its glycosylation and immunogen features, has the major impact on bnAb development.
Richardson2019
(antibody generation, antibody interactions, effector function, review, antibody lineage, antibody polyreactivity, broad neutralizer)
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BF520.1: The study identified 21 matured bnAb heavy chain (HC) lineage members from pediatric elite neutralizer AIIMS-330, from whom previous bnAb AIIMS-P01 was isolated. These 21 HC sequences shared the same clonotype with AIIMS-P01, with varied and moderate levels (30 - 47 nt) of somatic hypermutation. Using ARMADiLLo analysis, one HC (clone#16) stood out by the presence of 4 highly improbable mutations. In comparison to two other pediatric bnAbs (AIIMS-P01 and BF520.1), this HC exhibited a higher level of somatic hypermutation (15.2%).
Kumar2023
(responses in children, antibody lineage, germline)
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BF520.1: HIV-1 bnAbs require high levels of activation-induced cytidine deaminase (AID)-catalyzed somatic mutations. Probable mutations occur at sites of frequent AID activity, while improbable mutations occur where AID activity is infrequent. The paper introduced the ARMADiLLO program, which estimates how probable a particular mAb mutation is, and thus the key improbable mutations were defined for a panel of 26 bnAbs. The number of improbable mutations ranged from 7 (PGT128) to 23 (VRC01 and 35O22); BF520.1 had 12 improbable mutations out of 24 total AA mutations, and 0 indels. Single-amino acid reversion mutants were made for key improbable mutations of 3 bnAbs (CH235, VRC01, and BF520.1), and these mutant mAbs were tested for their neutralization ability. The study also noted that bnAbs that had relatively small numbers of improbable single somatic mutations had other unusual characteristics that were due to additional improbable events, such as indels (PGT128) or extraordinary CDR H3 lengths (VRC26.25).
Wiehe2018
(neutralization)
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BF520.1: The developmental lineage of BF520.1 was studied using computational methods developed for this purpose. The BF520.1 inferred naive precursor binds HIV Env. Heterologous cross-clade neutralizing activity evolved in the infant within 6 months of infection and, ultimately, only 2% SHM is needed to achieve the full breadth of the mature antibody. Mutagenesis and structural analyses reveal that substitutions in the kappa chain were critical for activity, particularly in CDRL1. Based on the analysis of many pairings of inferred intermediates, the study derived a minimal version of the antibody (Minimal BF520.1), which has and overall SHM of 2% (1.3% nt in MinimalVH and 2.7% nt in MinimalVK), which exhibited comparable breadth and potency to the mature bnAb. Overall, the developmental pathway of this infant antibody includes features distinct from adult antibodies, including several that may be amenable to better vaccine responses.
Simonich2019
(neutralization, computational prediction, responses in children, structure, antibody lineage)
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BF520.1: Ten mAbs were isolated from a vertically-infected infant at 15 months of age. Ab BF520.1 neutralized pseudoviruses from clades A, B and C with a breadth of 58%, putting it in the same range as second-generation bnAbs derived from adults, but its potency was lower. BF520.1 had a geometric mean of IC50=1.95 µg/ml for 7 viruses it neutralized. It was shown to target the base of the V3 loop at the N332 supersite. The infant-derived antibodies had a lower rate of somatic hypermutation (SHM) and no indels compared to adult-derived anti-V3 mAbs. This study shows that bnAbs can develop without SHM or prolonged affinity maturation.
Simonich2016
(antibody generation, neutralization, structure)
References
Showing 5 of
5 references.
Isolation Paper
Simonich2016
Cassandra A. Simonich, Katherine L. Williams, Hans P. Verkerke, James A. Williams, Ruth Nduati, Kelly K. Lee, and Julie Overbaugh. HIV-1 Neutralizing Antibodies with Limited Hypermutation from an Infant. Cell, 166(1):77-87, 30 Jun 2016. PubMed ID: 27345369.
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Kumar2023
Sanjeev Kumar, Swarandeep Singh, Arnab Chatterjee, Prashant Bajpai, Shaifali Sharma, Sanket Katpara, Rakesh Lodha, Somnath Dutta, and Kalpana Luthra. Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody. iScience, 26(9):107579 doi, Sep 2023. PubMed ID: 37649696
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Simonich2019
Cassandra A. Simonich, Laura Doepker, Duncan Ralph, James A. Williams, Amrit Dhar, Zak Yaffe, Lauren Gentles, Christopher T. Small, Brian Oliver, Vladimir Vigdorovich, Vidya Mangala Prasad, Ruth Nduati, D. Noah Sather, Kelly K. Lee, Frederick A. Matsen, IV, and Julie Overbaugh. Kappa Chain Maturation Helps Drive Rapid Development of an Infant HIV-1 Broadly Neutralizing Antibody Lineage. Nat. Commun., 10(1):2190, 16 May 2019. PubMed ID: 31097697.
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Wiehe2018
Kevin Wiehe, Todd Bradley, R. Ryan Meyerhoff, Connor Hart, Wilton B. Williams, David Easterhoff, William J. Faison, Thomas B. Kepler, Kevin O. Saunders, S. Munir Alam, Mattia Bonsignori, and Barton F. Haynes. Functional Relevance of Improbable Antibody Mutations for HIV Broadly Neutralizing Antibody Development. Cell Host Microbe, 23(6):759-765.e6, 13 Jun 2018. PubMed ID: 29861171.
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Richardson2019
Simone I. Richardson, and Penny L. Moore. The antibody response in HIV-1-infected donors. Curr Opin HIV AIDS, 14(4):233-239 doi, Jul 2019. PubMed ID: 31033730
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