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Article

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

1
Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59715, USA
2
Research Institute for Children, Children’s Hospital, New Orleans, LA 70118, USA
3
Department of Pathology, Tulane University, New Orleans, LA 70112, USA
4
Department of Surgery, Duke University, Durham, NC 27707, USA
5
Department of Microbiology, Immunology, and Parasitology, LSU School of Medicine, New Orleans, LA 70112, USA
*
Author to whom correspondence should be addressed.
Vaccines 2021, 9(7), 774; https://doi.org/10.3390/vaccines9070774
Submission received: 1 June 2021 / Revised: 2 July 2021 / Accepted: 5 July 2021 / Published: 12 July 2021
(This article belongs to the Special Issue Advances in Antibody Based HIV-1 Vaccine Development)

Abstract

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.
Keywords: HIV; immunotherapy; immunoadhesin; AIDS HIV; immunotherapy; immunoadhesin; AIDS

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MDPI and ACS Style

Pincus, S.H.; Craig, R.B.; Weachter, L.; LaBranche, C.C.; Nabi, R.; Watt, C.; Raymond, M.; Peters, T.; Song, K.; Maresh, G.A.; et al. Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity. Vaccines 2021, 9, 774. https://doi.org/10.3390/vaccines9070774

AMA Style

Pincus SH, Craig RB, Weachter L, LaBranche CC, Nabi R, Watt C, Raymond M, Peters T, Song K, Maresh GA, et al. Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity. Vaccines. 2021; 9(7):774. https://doi.org/10.3390/vaccines9070774

Chicago/Turabian Style

Pincus, Seth H., Ryan B. Craig, Lauren Weachter, Celia C. LaBranche, Rafiq Nabi, Connie Watt, Mark Raymond, Tami Peters, Kejing Song, Grace A. Maresh, and et al. 2021. "Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity" Vaccines 9, no. 7: 774. https://doi.org/10.3390/vaccines9070774

APA Style

Pincus, S. H., Craig, R. B., Weachter, L., LaBranche, C. C., Nabi, R., Watt, C., Raymond, M., Peters, T., Song, K., Maresh, G. A., Montefiori, D. C., & Kozlowski, P. A. (2021). Bispecific Anti-HIV Immunoadhesins That Bind Gp120 and Gp41 Have Broad and Potent HIV-Neutralizing Activity. Vaccines, 9(7), 774. https://doi.org/10.3390/vaccines9070774

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