Characterization and Immunogenicity of HIV Envelope gp140 Zera® Tagged Antigens
HIV-1 envelope glycoprotein (Env) remains the most relevant target for the elicitation of functional antibodies to HIV by vaccination. However, soluble Env antigens often do not elicit the desired immune responses. Delivering subunit antigens on particulate nanoparticles is an established approach t...
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Language: | English |
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Frontiers Media S.A.
2020-04-01
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Series: | Frontiers in Bioengineering and Biotechnology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2020.00321/full |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Phindile Ximba Phindile Ximba Phindile Ximba Rosamund Chapman Rosamund Chapman Ann E. Meyers Emmanuel Margolin Emmanuel Margolin Emmanuel Margolin Michiel T. van Diepen Michiel T. van Diepen Anna-Lise Williamson Anna-Lise Williamson Edward P. Rybicki Edward P. Rybicki |
spellingShingle |
Phindile Ximba Phindile Ximba Phindile Ximba Rosamund Chapman Rosamund Chapman Ann E. Meyers Emmanuel Margolin Emmanuel Margolin Emmanuel Margolin Michiel T. van Diepen Michiel T. van Diepen Anna-Lise Williamson Anna-Lise Williamson Edward P. Rybicki Edward P. Rybicki Characterization and Immunogenicity of HIV Envelope gp140 Zera® Tagged Antigens Frontiers in Bioengineering and Biotechnology HIV-1 protein body envelope protein vaccine Zera® immunogenicity |
author_facet |
Phindile Ximba Phindile Ximba Phindile Ximba Rosamund Chapman Rosamund Chapman Ann E. Meyers Emmanuel Margolin Emmanuel Margolin Emmanuel Margolin Michiel T. van Diepen Michiel T. van Diepen Anna-Lise Williamson Anna-Lise Williamson Edward P. Rybicki Edward P. Rybicki |
author_sort |
Phindile Ximba |
title |
Characterization and Immunogenicity of HIV Envelope gp140 Zera® Tagged Antigens |
title_short |
Characterization and Immunogenicity of HIV Envelope gp140 Zera® Tagged Antigens |
title_full |
Characterization and Immunogenicity of HIV Envelope gp140 Zera® Tagged Antigens |
title_fullStr |
Characterization and Immunogenicity of HIV Envelope gp140 Zera® Tagged Antigens |
title_full_unstemmed |
Characterization and Immunogenicity of HIV Envelope gp140 Zera® Tagged Antigens |
title_sort |
characterization and immunogenicity of hiv envelope gp140 zera® tagged antigens |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Bioengineering and Biotechnology |
issn |
2296-4185 |
publishDate |
2020-04-01 |
description |
HIV-1 envelope glycoprotein (Env) remains the most relevant target for the elicitation of functional antibodies to HIV by vaccination. However, soluble Env antigens often do not elicit the desired immune responses. Delivering subunit antigens on particulate nanoparticles is an established approach to improve their immunogenicity. In this study the sequence encoding Zera®, a proline-rich domain derived from the γ-zein storage protein, was fused to either the C- or N-terminus of the superinfecting HIV-1 CAP256 gp140 envelope: Zera® generally induces the formation of protein bodies (PBs), which can significantly improve both the immunogenicity and yields of the partner protein. The expression of gp140-Zera® and Zera®-gp140 (N- and C-terminal fusions respectively) in mammalian cells was confirmed by western blot analysis and immunostaining. However, isopycnic ultracentrifugation showed that neither gp140-Zera® nor Zera®-gp140 accumulated in characteristic electron-dense PBs. gp140-Zera® elicited higher binding antibody titers in rabbits to autologous gp140 and V1V2 scaffold than Zera®-gp140. Rabbit anti-gp140-Zera® sera also had significantly higher Tier 1A neutralizing antibody titers than anti-Zera®-gp140 sera. Neither gp140-Zera® nor Zera®-gp140-specific sera neutralized Tier 1B or autologous Tier 2 viruses. These results showed that HIV-1 gp140 tagged with Zera® at either the N- or C-termini elicited high titers of gp140 and V1V2 binding antibodies, and low levels of Tier 1 neutralizing antibodies in rabbits. |
topic |
HIV-1 protein body envelope protein vaccine Zera® immunogenicity |
url |
https://www.frontiersin.org/article/10.3389/fbioe.2020.00321/full |
work_keys_str_mv |
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doaj-d86c002d4a024480833e43e37108f00d2020-11-25T02:26:36ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-04-01810.3389/fbioe.2020.00321512410Characterization and Immunogenicity of HIV Envelope gp140 Zera® Tagged AntigensPhindile Ximba0Phindile Ximba1Phindile Ximba2Rosamund Chapman3Rosamund Chapman4Ann E. Meyers5Emmanuel Margolin6Emmanuel Margolin7Emmanuel Margolin8Michiel T. van Diepen9Michiel T. van Diepen10Anna-Lise Williamson11Anna-Lise Williamson12Edward P. Rybicki13Edward P. Rybicki14Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaBiopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaDivision of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaBiopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South AfricaDivision of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaBiopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaDivision of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaDivision of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaBiopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Cape Town, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South AfricaHIV-1 envelope glycoprotein (Env) remains the most relevant target for the elicitation of functional antibodies to HIV by vaccination. However, soluble Env antigens often do not elicit the desired immune responses. Delivering subunit antigens on particulate nanoparticles is an established approach to improve their immunogenicity. In this study the sequence encoding Zera®, a proline-rich domain derived from the γ-zein storage protein, was fused to either the C- or N-terminus of the superinfecting HIV-1 CAP256 gp140 envelope: Zera® generally induces the formation of protein bodies (PBs), which can significantly improve both the immunogenicity and yields of the partner protein. The expression of gp140-Zera® and Zera®-gp140 (N- and C-terminal fusions respectively) in mammalian cells was confirmed by western blot analysis and immunostaining. However, isopycnic ultracentrifugation showed that neither gp140-Zera® nor Zera®-gp140 accumulated in characteristic electron-dense PBs. gp140-Zera® elicited higher binding antibody titers in rabbits to autologous gp140 and V1V2 scaffold than Zera®-gp140. Rabbit anti-gp140-Zera® sera also had significantly higher Tier 1A neutralizing antibody titers than anti-Zera®-gp140 sera. Neither gp140-Zera® nor Zera®-gp140-specific sera neutralized Tier 1B or autologous Tier 2 viruses. These results showed that HIV-1 gp140 tagged with Zera® at either the N- or C-termini elicited high titers of gp140 and V1V2 binding antibodies, and low levels of Tier 1 neutralizing antibodies in rabbits.https://www.frontiersin.org/article/10.3389/fbioe.2020.00321/fullHIV-1protein bodyenvelope proteinvaccineZera®immunogenicity |