Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4+/CD8+ T cells and humoral responses in macaques
Abstract Inducing humoral, cellular and mucosal immunity is likely to improve the effectiveness of HIV-1 vaccine strategies. Here, we tested a vaccine regimen in pigtail macaques using an intranasal (i.n.) recombinant Fowl Pox Virus (FPV)-gag pol env-IL-4R antagonist prime, intramuscular (i.m.) reco...
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doaj-0291f314d0d046248dbf0e7b08dc85902020-12-20T12:33:10ZengNature Publishing GroupScientific Reports2045-23222020-12-0110111810.1038/s41598-020-79172-7Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4+/CD8+ T cells and humoral responses in macaquesZ. Li0M. Khanna1S. L. Grimley2P. Ellenberg3C. A. Gonelli4Wen Shi Lee5T. H. Amarasena6A. D. Kelleher7D. F. J. Purcell8S. J. Kent9C. Ranasinghe10Molecular Mucosal Vaccine Immunology Group, Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National UniversityMolecular Mucosal Vaccine Immunology Group, Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National UniversityDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneImmunovirology and Pathogenesis Program, Kirby Institute, University of New South WalesDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of MelbourneMolecular Mucosal Vaccine Immunology Group, Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National UniversityAbstract Inducing humoral, cellular and mucosal immunity is likely to improve the effectiveness of HIV-1 vaccine strategies. Here, we tested a vaccine regimen in pigtail macaques using an intranasal (i.n.) recombinant Fowl Pox Virus (FPV)-gag pol env-IL-4R antagonist prime, intramuscular (i.m.) recombinant Modified Vaccinia Ankara Virus (MVA)-gag pol-IL-4R antagonist boost followed by an i.m SOSIP-gp140 boost. The viral vector—expressed IL-4R antagonist transiently inhibited IL-4/IL-13 signalling at the vaccination site. The SOSIP booster not only induced gp140-specific IgG, ADCC (antibody-dependent cellular cytotoxicity) and some neutralisation activity, but also bolstered the HIV-specific cellular and humoral responses. Specifically, superior sustained systemic and mucosal HIV Gag-specific poly-functional/cytotoxic CD4+ and CD8+ T cells were detected with the IL-4R antagonist adjuvanted strategy compared to the unadjuvanted control. In the systemic compartment elevated Granzyme K expression was linked to CD4+ T cells, whilst Granzyme B/TIA-1 to CD8+ T cells. In contrast, the cytotoxic marker expression by mucosal CD4+ and CD8+ T cells differed according to the mucosal compartment. This vector-based mucosal IL-4R antagonist/SOSIP booster strategy, which promotes cytotoxic mucosal CD4+ T cells at the first line of defence, and cytotoxic CD4+ and CD8+ T cells plus functional antibodies in the blood, may prove valuable in combating mucosal infection with HIV-1 and warrants further investigation.https://doi.org/10.1038/s41598-020-79172-7 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Z. Li M. Khanna S. L. Grimley P. Ellenberg C. A. Gonelli Wen Shi Lee T. H. Amarasena A. D. Kelleher D. F. J. Purcell S. J. Kent C. Ranasinghe |
spellingShingle |
Z. Li M. Khanna S. L. Grimley P. Ellenberg C. A. Gonelli Wen Shi Lee T. H. Amarasena A. D. Kelleher D. F. J. Purcell S. J. Kent C. Ranasinghe Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4+/CD8+ T cells and humoral responses in macaques Scientific Reports |
author_facet |
Z. Li M. Khanna S. L. Grimley P. Ellenberg C. A. Gonelli Wen Shi Lee T. H. Amarasena A. D. Kelleher D. F. J. Purcell S. J. Kent C. Ranasinghe |
author_sort |
Z. Li |
title |
Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4+/CD8+ T cells and humoral responses in macaques |
title_short |
Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4+/CD8+ T cells and humoral responses in macaques |
title_full |
Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4+/CD8+ T cells and humoral responses in macaques |
title_fullStr |
Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4+/CD8+ T cells and humoral responses in macaques |
title_full_unstemmed |
Mucosal IL-4R antagonist HIV vaccination with SOSIP-gp140 booster can induce high-quality cytotoxic CD4+/CD8+ T cells and humoral responses in macaques |
title_sort |
mucosal il-4r antagonist hiv vaccination with sosip-gp140 booster can induce high-quality cytotoxic cd4+/cd8+ t cells and humoral responses in macaques |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2020-12-01 |
description |
Abstract Inducing humoral, cellular and mucosal immunity is likely to improve the effectiveness of HIV-1 vaccine strategies. Here, we tested a vaccine regimen in pigtail macaques using an intranasal (i.n.) recombinant Fowl Pox Virus (FPV)-gag pol env-IL-4R antagonist prime, intramuscular (i.m.) recombinant Modified Vaccinia Ankara Virus (MVA)-gag pol-IL-4R antagonist boost followed by an i.m SOSIP-gp140 boost. The viral vector—expressed IL-4R antagonist transiently inhibited IL-4/IL-13 signalling at the vaccination site. The SOSIP booster not only induced gp140-specific IgG, ADCC (antibody-dependent cellular cytotoxicity) and some neutralisation activity, but also bolstered the HIV-specific cellular and humoral responses. Specifically, superior sustained systemic and mucosal HIV Gag-specific poly-functional/cytotoxic CD4+ and CD8+ T cells were detected with the IL-4R antagonist adjuvanted strategy compared to the unadjuvanted control. In the systemic compartment elevated Granzyme K expression was linked to CD4+ T cells, whilst Granzyme B/TIA-1 to CD8+ T cells. In contrast, the cytotoxic marker expression by mucosal CD4+ and CD8+ T cells differed according to the mucosal compartment. This vector-based mucosal IL-4R antagonist/SOSIP booster strategy, which promotes cytotoxic mucosal CD4+ T cells at the first line of defence, and cytotoxic CD4+ and CD8+ T cells plus functional antibodies in the blood, may prove valuable in combating mucosal infection with HIV-1 and warrants further investigation. |
url |
https://doi.org/10.1038/s41598-020-79172-7 |
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