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Rational design of membrane proximal external region lipopeptides containing chemical modifications for HIV-1 vaccination.

Publication ,  Journal Article
Venditto, VJ; Watson, DS; Motion, M; Montefiori, D; Szoka, FC
Published in: Clin Vaccine Immunol
January 2013

The inability to generate broadly neutralizing antibody (bnAb) responses to the membrane proximal external region (MPER) of HIV-1 gp41 using current vaccine strategies has hampered efforts to prevent the spread of HIV. To address this challenge, we investigated a novel hypothesis to help improve the anti-MPER antibody response. Guided by structural insights and the unique lipid reactivity of anti-MPER bnAbs, we considered whether amino acid side chain modifications that emulate hydrophilic phospholipid head groups could contribute to the generation of 2F5-like or 4E10-like neutralizing anti-MPER antibodies. To test this hypothesis, we generated a series of chemically modified MPER immunogens through derivatization of amino acid side chains with phosphate or nitrate groups. We evaluated the binding affinity of the chemically modified peptides to their cognate monoclonal antibodies, 2F5 and 4E10, using surface plasmon resonance. The modifications had little effect on binding to the antibodies and did not influence epitope secondary structure when presented in liposomes. We selected five of the chemically modified sequences to immunize rabbits and found that an immunogen containing both the 2F5 and 4E10 epitopes and a phosphorylated threonine at T676 elicited the highest anti-peptide IgG titers, although the high antipeptide titers did not confer higher neutralizing activity. These data indicate that side chain modifications adjacent to known neutralizing antibody epitopes are capable of eliciting antibody responses to the MPER but that these chemically modified gp41 epitopes do not induce neutralizing antibodies.

Duke Scholars

Published In

Clin Vaccine Immunol

DOI

EISSN

1556-679X

Publication Date

January 2013

Volume

20

Issue

1

Start / End Page

39 / 45

Location

United States

Related Subject Headings

  • Vaccination
  • Rabbits
  • Microbiology
  • Lipopeptides
  • Immunology
  • Immunoglobulin G
  • HIV Envelope Protein gp41
  • HIV Antibodies
  • Drug Design
  • Antibodies, Neutralizing
 

Citation

APA
Chicago
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MLA
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Venditto, V. J., Watson, D. S., Motion, M., Montefiori, D., & Szoka, F. C. (2013). Rational design of membrane proximal external region lipopeptides containing chemical modifications for HIV-1 vaccination. Clin Vaccine Immunol, 20(1), 39–45. https://doi.org/10.1128/CVI.00615-12
Venditto, Vincent J., Douglas S. Watson, Michael Motion, David Montefiori, and Francis C. Szoka. “Rational design of membrane proximal external region lipopeptides containing chemical modifications for HIV-1 vaccination.Clin Vaccine Immunol 20, no. 1 (January 2013): 39–45. https://doi.org/10.1128/CVI.00615-12.
Venditto VJ, Watson DS, Motion M, Montefiori D, Szoka FC. Rational design of membrane proximal external region lipopeptides containing chemical modifications for HIV-1 vaccination. Clin Vaccine Immunol. 2013 Jan;20(1):39–45.
Venditto, Vincent J., et al. “Rational design of membrane proximal external region lipopeptides containing chemical modifications for HIV-1 vaccination.Clin Vaccine Immunol, vol. 20, no. 1, Jan. 2013, pp. 39–45. Pubmed, doi:10.1128/CVI.00615-12.
Venditto VJ, Watson DS, Motion M, Montefiori D, Szoka FC. Rational design of membrane proximal external region lipopeptides containing chemical modifications for HIV-1 vaccination. Clin Vaccine Immunol. 2013 Jan;20(1):39–45.

Published In

Clin Vaccine Immunol

DOI

EISSN

1556-679X

Publication Date

January 2013

Volume

20

Issue

1

Start / End Page

39 / 45

Location

United States

Related Subject Headings

  • Vaccination
  • Rabbits
  • Microbiology
  • Lipopeptides
  • Immunology
  • Immunoglobulin G
  • HIV Envelope Protein gp41
  • HIV Antibodies
  • Drug Design
  • Antibodies, Neutralizing