Format

Send to

Choose Destination
Sci Rep. 2019 Apr 5;9(1):5661. doi: 10.1038/s41598-019-41506-5.

Mucosal and systemic SIV-specific cytotoxic CD4+ T cell hierarchy in protection following intranasal/intramuscular recombinant pox-viral vaccination of pigtail macaques.

Author information

1
Molecular Mucosal Vaccine Immunology Group, Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra ACT, 2601, Australia.
2
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.
3
Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC, 3010, Australia.
4
Immunovirology and Pathogenesis Program, Kirby Institute, University of New South Wales, Sydney, NSW, 2052, Australia.
5
Molecular Mucosal Vaccine Immunology Group, Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra ACT, 2601, Australia. Charani.Ranasinge@anu.edu.au.

Abstract

A HIV vaccine that provides mucosal immunity is urgently needed. We evaluated an intranasal recombinant Fowlpox virus (rFPV) priming vaccine followed by intramuscular Modified Vaccinia Ankara (rMVA) booster vaccine, both expressing SIV antigens. The vaccination generated mucosal and systemic SIV-specific CD4+ T cell mediated immunity and was associated with partial protection against high-dose intrarectal SIVmac251 challenge in outbred pigtail macaques. Three of 12 vaccinees were completely protected and these animals elicited sustained Gag-specific poly-functional, cytotoxic mucosal CD4+ T cells, complemented by systemic poly-functional CD4+ and CD8+ T cell immunity. Humoral immune responses, albeit absent in completely protected macaques, were associated with partial control of viremia in animals with relatively weaker mucosal/systemic T cell responses. Co-expression of an IL-4R antagonist by the rFPV vaccine further enhanced the breadth and cytotoxicity/poly-functionality of mucosal vaccine-specific CD4+ T cells. Moreover, a single FPV-gag/pol/env prime was able to induce rapid anamnestic gp140 antibody response upon SIV encounter. Collectively, our data indicated that nasal vaccination was effective at inducing robust cervico-vaginal and rectal immunity, although cytotoxic CD4+ T cell mediated mucosal and systemic immunity correlated strongly with 'complete protection', the different degrees of protection observed was multi-factorial.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center