Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1
Author(s)
Type
Journal Article
Abstract
To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.
Date Issued
2014-12-18
Date Acceptance
2014-11-04
Citation
PLoS Pathogens, 2014, 10 (12)
ISSN
1553-7366
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Pathogens
Volume
10
Issue
12
Copyright Statement
© 2014 McCoy et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000346702400036&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
B-CELL RECEPTORS
MONOCLONAL-ANTIBODIES
STRUCTURAL BASIS
IN-VIVO
VECTORED IMMUNOPROPHYLAXIS
SHIV TRANSMISSION
ENVELOPE PROTEIN
RATIONAL DESIGN
HUMANIZED MICE
POTENT
Publication Status
Published
Article Number
e1004552
Date Publish Online
2014-12-18