Volume 9 Supplement 2

AIDS Vaccine 2012

Open Access

Broad and potent neutralization of HIV-1 by human-llama fusion antibodies derived from immunized llamas

  • LE McCoy1,
  • L Rutten2,
  • G Dekkers1,
  • C Blanchetot3,
  • NM Strokappe4,
  • A Forsman-Quigley1,
  • MS Seaman5,
  • H de Haard3,
  • T Verrips4 and
  • RA Weiss1
Retrovirology20129(Suppl 2):P94

DOI: 10.1186/1742-4690-9-S2-P94

Published: 13 September 2012

Background

Llamas naturally produce heavy chain only antibodies in addition to conventional antibodies. The variable regions of the heavy chain (VHH) demonstrate comparable affinity and specificity for antigens with conventional immunoglobulins. To date, immunizations in human and animal models have yielded only antibodies with limited ability to neutralize human immunodeficiency virus (HIV)-1.

Methods

A VHH (J3) isolated from a llama multiply-immunized with recombinant trimeric HIV-1 envelope proteins (Env) was found to neutralize 96 of 100 HIV-1 strains, encompassing subtypes A, B, C, D, BC, AE, AG, AC, ACD, CD and G. Isolation involved expression of VHH in E. coli and analysis of neutralization ability in TZM-bl reporter cells.

Results

Newly isolated VHH from multiple immunized llamas also have broad and potent HIV-1 neutralization activity. J3 targets HIV-1 via the CD4-binding site and neutralization is seen when J3 is used in combination with VHH targeting other Env epitopes. VHH-human FC fusion heavy-chain only antibodies (VHH-FC) have been constructed and J3 activity is not only preserved in this context but enhanced.

Conclusion

This study shows that experimental immunization with recombinant HIV-1 Env can elicit broad neutralizing heavy-chain only antibodies and supports the development of VHH and VHH-FC as anti-HIV-1 microbicides and therapeutics.

Authors’ Affiliations

(1)
University College London
(2)
Biomolecular Imaging, Department Biology, University of Utrecht
(3)
arGEN-X BVBA
(4)
Biomolecular Imaging, Department Biology, Utrecht University
(5)
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center

Copyright

© McCoy et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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