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Identification of human monoclonal antibodies specific for CCR5 from an antibody library derived from HIV-infected long-term non-progressors

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It has been reported that about one quarter of long-term nonprogressors had anti-CCR5 antibodies and such antibodies were not found in disease progressing HIV-1 positive individuals [1]. To identify such antibodies we panned an HIV immune library constructed from bone marrow of three long-term nonprogressors against a synthetic sulfated N-terminal CCR5 peptide (2–15) (R5Nt). Twenty anti-CCR5 monoclonal antibodies were selected that bind to the R5Nt and cell-associated CCR5. Sequence analysis revealed that eighteen clones have VHs that were derived from the same germline sequence. Preliminary data showed that these antibodies inhibited primary HIV-1 isolates from clade B and E as tested in a pseudovirus assay. Identification of these anti-CCR5 human monoclonal antibodies indicates possible contribution to mechanisms determining the slow progression or lack of disease in long-term nonprogresssors. The selected anti-CCR5 antibodies may have potentials as therapeutics and/or prophylactics in combination with other HIV-1 neutralizing antibodies and antiretroviral drugs.

References

  1. 1.

    Pastori C, Weiser B, Barassi C: Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression. Blood. 107: 4825-4833. 10.1182/blood-2005-06-2463.

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Correspondence to Mei-Yun Zhang.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://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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Keywords

  • Neutralize Antibody
  • Human Monoclonal Antibody
  • Slow Progression
  • Positive Individual
  • Antibody Library