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Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection

Stimulating broadly neutralizing antibodies (bnAbs) directly from germline remains a barrier for HIV vaccines. HIV superinfection elicits bnAbs more frequently than single infection, providing clues of how to elicit such responses. We used longitudinal antibody sequencing and structural studies to c...

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Autores principales: Shipley, Mackenzie M, Mangala Prasad, Vidya, Doepker, Laura E, Dingens, Adam, Ralph, Duncan K, Harkins, Elias, Dhar, Amrit, Arenz, Dana, Chohan, Vrasha, Weight, Haidyn, Mandaliya, Kishor, Bloom, Jesse D, Matsen, Frederick A, Lee, Kelly K, Overbaugh, Julie M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376252/
https://www.ncbi.nlm.nih.gov/pubmed/34263727
http://dx.doi.org/10.7554/eLife.68110
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author Shipley, Mackenzie M
Mangala Prasad, Vidya
Doepker, Laura E
Dingens, Adam
Ralph, Duncan K
Harkins, Elias
Dhar, Amrit
Arenz, Dana
Chohan, Vrasha
Weight, Haidyn
Mandaliya, Kishor
Bloom, Jesse D
Matsen, Frederick A
Lee, Kelly K
Overbaugh, Julie M
author_facet Shipley, Mackenzie M
Mangala Prasad, Vidya
Doepker, Laura E
Dingens, Adam
Ralph, Duncan K
Harkins, Elias
Dhar, Amrit
Arenz, Dana
Chohan, Vrasha
Weight, Haidyn
Mandaliya, Kishor
Bloom, Jesse D
Matsen, Frederick A
Lee, Kelly K
Overbaugh, Julie M
author_sort Shipley, Mackenzie M
collection PubMed
description Stimulating broadly neutralizing antibodies (bnAbs) directly from germline remains a barrier for HIV vaccines. HIV superinfection elicits bnAbs more frequently than single infection, providing clues of how to elicit such responses. We used longitudinal antibody sequencing and structural studies to characterize bnAb development from a superinfection case. BnAb QA013.2 bound initial and superinfecting viral Env, despite its probable naive progenitor only recognizing the superinfecting strain, suggesting both viruses influenced this lineage. A 4.15 Å cryo-EM structure of QA013.2 bound to native-like trimer showed recognition of V3 signatures (N301/N332 and GDIR). QA013.2 relies less on CDRH3 and more on framework and CDRH1 for affinity and breadth compared to other V3/glycan-specific bnAbs. Antigenic profiling revealed that viral escape was achieved by changes in the structurally-defined epitope and by mutations in V1. These results highlight shared and novel properties of QA013.2 relative to other V3/glycan-specific bnAbs in the setting of sequential, diverse antigens.
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spelling pubmed-83762522021-08-20 Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection Shipley, Mackenzie M Mangala Prasad, Vidya Doepker, Laura E Dingens, Adam Ralph, Duncan K Harkins, Elias Dhar, Amrit Arenz, Dana Chohan, Vrasha Weight, Haidyn Mandaliya, Kishor Bloom, Jesse D Matsen, Frederick A Lee, Kelly K Overbaugh, Julie M eLife Microbiology and Infectious Disease Stimulating broadly neutralizing antibodies (bnAbs) directly from germline remains a barrier for HIV vaccines. HIV superinfection elicits bnAbs more frequently than single infection, providing clues of how to elicit such responses. We used longitudinal antibody sequencing and structural studies to characterize bnAb development from a superinfection case. BnAb QA013.2 bound initial and superinfecting viral Env, despite its probable naive progenitor only recognizing the superinfecting strain, suggesting both viruses influenced this lineage. A 4.15 Å cryo-EM structure of QA013.2 bound to native-like trimer showed recognition of V3 signatures (N301/N332 and GDIR). QA013.2 relies less on CDRH3 and more on framework and CDRH1 for affinity and breadth compared to other V3/glycan-specific bnAbs. Antigenic profiling revealed that viral escape was achieved by changes in the structurally-defined epitope and by mutations in V1. These results highlight shared and novel properties of QA013.2 relative to other V3/glycan-specific bnAbs in the setting of sequential, diverse antigens. eLife Sciences Publications, Ltd 2021-07-15 /pmc/articles/PMC8376252/ /pubmed/34263727 http://dx.doi.org/10.7554/eLife.68110 Text en © 2021, Shipley et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Shipley, Mackenzie M
Mangala Prasad, Vidya
Doepker, Laura E
Dingens, Adam
Ralph, Duncan K
Harkins, Elias
Dhar, Amrit
Arenz, Dana
Chohan, Vrasha
Weight, Haidyn
Mandaliya, Kishor
Bloom, Jesse D
Matsen, Frederick A
Lee, Kelly K
Overbaugh, Julie M
Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection
title Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection
title_full Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection
title_fullStr Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection
title_full_unstemmed Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection
title_short Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection
title_sort functional development of a v3/glycan-specific broadly neutralizing antibody isolated from a case of hiv superinfection
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376252/
https://www.ncbi.nlm.nih.gov/pubmed/34263727
http://dx.doi.org/10.7554/eLife.68110
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