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Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity.

Publication ,  Journal Article
Pincus, SH; Craig, RB; Weachter, L; LaBranche, CC; Nabi, R; Watt, C; Raymond, M; Peters, T; Song, K; Maresh, GA; Montefiori, DC; Kozlowski, PA
Published in: Vaccines (Basel)
July 12, 2021

We have constructed bispecific immunoglobulin-like immunoadhesins that bind to both the HIV-envelope glycoproteins: gp120 and gp41. These immunoadhesins have N terminal domains of human CD4 engrafted onto the N-terminus of the heavy chain of human anti-gp41 mAb 7B2. Binding of these constructs to recombinant Env and their antiviral activities were compared to that of the parental mAbs and CD4, as well as to control mAbs. The CD4/7B2 constructs bind to both gp41 and gp140, as well as to native Env expressed on the surface of infected cells. These constructs deliver cytotoxic immunoconjugates to HIV-infected cells, but not as well as a mixture of 7B2 and sCD4, and opsonize for antibody-mediated phagocytosis. Most surprisingly, given that 7B2 neutralizes weakly, if at all, is that the chimeric CD4/7B2 immunoadhesins exhibit broad and potent neutralization of HIV, comparable to that of well-known neutralizing mAbs. These data add to the growing evidence that enhanced neutralizing activity can be obtained with bifunctional mAbs/immunoadhesins. The enhanced neutralization activity of the CD4/7B2 chimeras may result from cross-linking of the two Env subunits with subsequent inhibition of the pre-fusion conformational events that are necessary for entry.

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Published In

Vaccines (Basel)

DOI

ISSN

2076-393X

Publication Date

July 12, 2021

Volume

9

Issue

7

Location

Switzerland

Related Subject Headings

  • 3207 Medical microbiology
  • 3204 Immunology
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
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Pincus, S. H., Craig, R. B., Weachter, L., LaBranche, C. C., Nabi, R., Watt, C., … Kozlowski, P. A. (2021). Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity. Vaccines (Basel), 9(7). https://doi.org/10.3390/vaccines9070774
Pincus, Seth H., Ryan B. Craig, Lauren Weachter, Celia C. LaBranche, Rafiq Nabi, Connie Watt, Mark Raymond, et al. “Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity.Vaccines (Basel) 9, no. 7 (July 12, 2021). https://doi.org/10.3390/vaccines9070774.
Pincus SH, Craig RB, Weachter L, LaBranche CC, Nabi R, Watt C, et al. Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity. Vaccines (Basel). 2021 Jul 12;9(7).
Pincus, Seth H., et al. “Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity.Vaccines (Basel), vol. 9, no. 7, July 2021. Pubmed, doi:10.3390/vaccines9070774.
Pincus SH, Craig RB, Weachter L, LaBranche CC, Nabi R, Watt C, Raymond M, Peters T, Song K, Maresh GA, Montefiori DC, Kozlowski PA. Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity. Vaccines (Basel). 2021 Jul 12;9(7).

Published In

Vaccines (Basel)

DOI

ISSN

2076-393X

Publication Date

July 12, 2021

Volume

9

Issue

7

Location

Switzerland

Related Subject Headings

  • 3207 Medical microbiology
  • 3204 Immunology
  • 3202 Clinical sciences