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The Envelope-Based Fusion Antigen GP120C14K Forming Hexamer-Like Structures Triggers T Cell and Neutralizing Antibody Responses Against HIV-1
There is an urgent need for the development of potent vaccination regimens that are able to induce specific T and B cell responses against human immunodeficiency virus type 1 (HIV-1). Here, we describe the generation and characterization of a fusion antigen comprised of the HIV-1 envelope GP120 glyc...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904342/ https://www.ncbi.nlm.nih.gov/pubmed/31867001 http://dx.doi.org/10.3389/fimmu.2019.02793 |
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author | Raman, Suresh C. Mejías-Pérez, Ernesto Gomez, Carmen E. García-Arriaza, Juan Perdiguero, Beatriz Vijayan, Aneesh Pérez-Ruiz, Mar Cuervo, Ana Santiago, César Sorzano, Carlos Oscar S. Sánchez-Corzo, Cristina Moog, Christiane Burger, Judith A. Schorcht, Anna Sanders, Rogier W. Carrascosa, José L. Esteban, Mariano |
author_facet | Raman, Suresh C. Mejías-Pérez, Ernesto Gomez, Carmen E. García-Arriaza, Juan Perdiguero, Beatriz Vijayan, Aneesh Pérez-Ruiz, Mar Cuervo, Ana Santiago, César Sorzano, Carlos Oscar S. Sánchez-Corzo, Cristina Moog, Christiane Burger, Judith A. Schorcht, Anna Sanders, Rogier W. Carrascosa, José L. Esteban, Mariano |
author_sort | Raman, Suresh C. |
collection | PubMed |
description | There is an urgent need for the development of potent vaccination regimens that are able to induce specific T and B cell responses against human immunodeficiency virus type 1 (HIV-1). Here, we describe the generation and characterization of a fusion antigen comprised of the HIV-1 envelope GP120 glycoprotein from clade C (GP120C) fused at its C-terminus, with the modified vaccinia virus (VACV) 14K protein (A27L gene) (termed GP120C14K). The design is directed toward improving the immunogenicity of the GP120C protein through its oligomerization facilitated by the fused VACV 14K protein that results in hexamer-like structures. Two different immunogens were generated: a recombinant GP120C14K fusion protein (purified from a stable CHO-K1 cell line) and a recombinant modified vaccinia virus Ankara (MVA) poxvirus vector expressing the GP120C14K fusion protein (termed MVA-GP120C14K). The GP120C14K fusion protein is recognized by broadly neutralizing antibodies (bNAbs) against HIV-1. In a murine model, a heterologous prime/boost immunization regimen with MVA-GP120C14K prime followed by adjuvanted GP120C14K protein boost generated stronger and polyfunctional HIV-1 Env-specific CD8 T cell responses when compared with the delivery of the monomeric GP120C form. Furthermore, the immunization protocol MVA-GP120C14K/GP120C14K elicited higher HIV-1 Env-specific T follicular helper cells, germinal center B cells and antibody responses than monomeric GP120. In addition, a similar MVA-GP120C14K prime/GP120C14K protein boost regimen performed in rabbits triggered high HIV-1-Env-specific IgG binding antibody titers that were capable of neutralizing HIV-1 pseudoviruses. The extent of HIV-1 neutralization was comparable to that elicited by the current standard GP140 SOSIP trimers from clades B and C when immunized as MVA-SOSIP prime/SOSIP protein boost regimen. Overall, the novel fusion antigen and the corresponding immunization scheme provided in this report can therefore be considered as potential vaccine strategies against HIV-1. |
format | Online Article Text |
id | pubmed-6904342 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69043422019-12-20 The Envelope-Based Fusion Antigen GP120C14K Forming Hexamer-Like Structures Triggers T Cell and Neutralizing Antibody Responses Against HIV-1 Raman, Suresh C. Mejías-Pérez, Ernesto Gomez, Carmen E. García-Arriaza, Juan Perdiguero, Beatriz Vijayan, Aneesh Pérez-Ruiz, Mar Cuervo, Ana Santiago, César Sorzano, Carlos Oscar S. Sánchez-Corzo, Cristina Moog, Christiane Burger, Judith A. Schorcht, Anna Sanders, Rogier W. Carrascosa, José L. Esteban, Mariano Front Immunol Immunology There is an urgent need for the development of potent vaccination regimens that are able to induce specific T and B cell responses against human immunodeficiency virus type 1 (HIV-1). Here, we describe the generation and characterization of a fusion antigen comprised of the HIV-1 envelope GP120 glycoprotein from clade C (GP120C) fused at its C-terminus, with the modified vaccinia virus (VACV) 14K protein (A27L gene) (termed GP120C14K). The design is directed toward improving the immunogenicity of the GP120C protein through its oligomerization facilitated by the fused VACV 14K protein that results in hexamer-like structures. Two different immunogens were generated: a recombinant GP120C14K fusion protein (purified from a stable CHO-K1 cell line) and a recombinant modified vaccinia virus Ankara (MVA) poxvirus vector expressing the GP120C14K fusion protein (termed MVA-GP120C14K). The GP120C14K fusion protein is recognized by broadly neutralizing antibodies (bNAbs) against HIV-1. In a murine model, a heterologous prime/boost immunization regimen with MVA-GP120C14K prime followed by adjuvanted GP120C14K protein boost generated stronger and polyfunctional HIV-1 Env-specific CD8 T cell responses when compared with the delivery of the monomeric GP120C form. Furthermore, the immunization protocol MVA-GP120C14K/GP120C14K elicited higher HIV-1 Env-specific T follicular helper cells, germinal center B cells and antibody responses than monomeric GP120. In addition, a similar MVA-GP120C14K prime/GP120C14K protein boost regimen performed in rabbits triggered high HIV-1-Env-specific IgG binding antibody titers that were capable of neutralizing HIV-1 pseudoviruses. The extent of HIV-1 neutralization was comparable to that elicited by the current standard GP140 SOSIP trimers from clades B and C when immunized as MVA-SOSIP prime/SOSIP protein boost regimen. Overall, the novel fusion antigen and the corresponding immunization scheme provided in this report can therefore be considered as potential vaccine strategies against HIV-1. Frontiers Media S.A. 2019-12-04 /pmc/articles/PMC6904342/ /pubmed/31867001 http://dx.doi.org/10.3389/fimmu.2019.02793 Text en Copyright © 2019 Raman, Mejías-Pérez, Gomez, García-Arriaza, Perdiguero, Vijayan, Pérez-Ruiz, Cuervo, Santiago, Sorzano, Sánchez-Corzo, Moog, Burger, Schorcht, Sanders, Carrascosa and Esteban. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Raman, Suresh C. Mejías-Pérez, Ernesto Gomez, Carmen E. García-Arriaza, Juan Perdiguero, Beatriz Vijayan, Aneesh Pérez-Ruiz, Mar Cuervo, Ana Santiago, César Sorzano, Carlos Oscar S. Sánchez-Corzo, Cristina Moog, Christiane Burger, Judith A. Schorcht, Anna Sanders, Rogier W. Carrascosa, José L. Esteban, Mariano The Envelope-Based Fusion Antigen GP120C14K Forming Hexamer-Like Structures Triggers T Cell and Neutralizing Antibody Responses Against HIV-1 |
title | The Envelope-Based Fusion Antigen GP120C14K Forming Hexamer-Like Structures Triggers T Cell and Neutralizing Antibody Responses Against HIV-1 |
title_full | The Envelope-Based Fusion Antigen GP120C14K Forming Hexamer-Like Structures Triggers T Cell and Neutralizing Antibody Responses Against HIV-1 |
title_fullStr | The Envelope-Based Fusion Antigen GP120C14K Forming Hexamer-Like Structures Triggers T Cell and Neutralizing Antibody Responses Against HIV-1 |
title_full_unstemmed | The Envelope-Based Fusion Antigen GP120C14K Forming Hexamer-Like Structures Triggers T Cell and Neutralizing Antibody Responses Against HIV-1 |
title_short | The Envelope-Based Fusion Antigen GP120C14K Forming Hexamer-Like Structures Triggers T Cell and Neutralizing Antibody Responses Against HIV-1 |
title_sort | envelope-based fusion antigen gp120c14k forming hexamer-like structures triggers t cell and neutralizing antibody responses against hiv-1 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904342/ https://www.ncbi.nlm.nih.gov/pubmed/31867001 http://dx.doi.org/10.3389/fimmu.2019.02793 |
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