Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant

Robert G Schaut; Tara L Grinnage-Pulley; Kevin J Esch; Angela J Toepp; Malcolm S Duthie; Randall F Howard; Steven G Reed; Christine A Petersen

doi:10.1016/j.vaccine.2016.09.016

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Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant

Journal article

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Peer reviewed

Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant

Robert G Schaut, Tara L Grinnage-Pulley, Kevin J Esch, Angela J Toepp, Malcolm S Duthie, Randall F Howard, Steven G Reed and Christine A Petersen

Vaccine, Vol.34(44), pp.5225-5234

10/17/2016

DOI: 10.1016/j.vaccine.2016.09.016

PMCID: PMC5053902

PMID: 27665354

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Abstract

•Vaccine-specific T cell responses limited during clinical VL.•TLR agonists recovered T cell effector functions in cells from Leishmania-infected dogs.•Rational vaccine selection to improve antigen-fatigued responses crucial for endemic areas. Visceral leishmaniasis (VL), caused by infection with the obligate intracellular protozoan parasite Leishmania infantum, is a fatal disease of dogs and humans. Protection against VL requires a T helper 1 (Th1) skewed CD4+ T response, but despite this knowledge, there are currently no approved-to-market vaccines for humans and only three veterinary-use vaccines globally. As VL progresses from asymptomatic to symptomatic, L. infantum–specific interferon gamma (IFNγ) driven-Th1 responses become dampened and a state of immune exhaustion established. T cell exhaustion and other immunoregulatory processes, starting during asymptomatic disease, are likely to hinder vaccine-induced responses if vaccine is administered to infected, but asymptomatic and seronegative, individuals. In this study we evaluated how immune exhaustion, shown previously by our group to worsen in concert with VL progression, effected the capacity of vaccine candidate antigen/toll-like receptor (TLR) agonist combinations to promote protective CD4+ T cell responses during progressive VL. In conjunction with Th1 responses, we also evaluated concomitant stimulation of immune-balanced IL-10 regulatory cytokine production by these vaccine products in progressive VL canine T cells. Vaccine antigen L111f in combination with TLR agonists significantly recovered CD4+ T cell IFNγ intracellular production in T cells from asymptomatic VL dogs. Vaccine antigen NS with TLR agonists significantly recovered CD4+ T cell production in both endemic control and VL dogs. Combinations of TLR agonists and vaccine antigens overcame L. infantum induced cellular exhaustion, allowing robust Th1 CD4+ T cell responses from symptomatic dogs that previously had dampened responses to antigen alone. Antigen-agonist adjuvants can be utilized to promote more robust vaccine responses from infected hosts in endemic areas where vaccination of asymptomatic, L. infantum-infected animals is likely.

Adjuvants

CD4+ T cells

Leishmania (L.) infantum

Toll-like receptor agonist

Cytokines

Details

Title: Subtitle: Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant
Creators: Robert G Schaut - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA
Tara L Grinnage-Pulley - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA
Kevin J Esch - Department of Veterinary Pathology, College of Veterinary Medicine, Iowa State University, Ames, IA 50011, USA
Angela J Toepp - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA
Malcolm S Duthie - Infectious Disease Research Institute, Seattle, WA 98102, USA
Randall F Howard - Infectious Disease Research Institute, Seattle, WA 98102, USA
Steven G Reed - Infectious Disease Research Institute, Seattle, WA 98102, USA
Christine A Petersen - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Vaccine, Vol.34(44), pp.5225-5234
DOI: 10.1016/j.vaccine.2016.09.016
PMID: 27665354
PMCID: PMC5053902
NLM abbreviation: Vaccine
ISSN: 0264-410X
eISSN: 1873-2518
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100001250, name: Morris Animal Foundation, award: DC13-501A; name: University of Iowa, College of Public Health; name: Department of Epidemiology; DOI: 10.13039/100000865, name: Bill and Melinda Gates Foundation, award: 631, 39129; DOI: 10.13039/100000002, name: National Institutes of Health, award: AI25038; name: Carver College of Medicine; name: Holden Comprehensive Cancer Center; name: Iowa City Veteran’s Administration Medical Center
Language: English
Date published: 10/17/2016
Academic Unit: Epidemiology; Internal Medicine
Record Identifier: 9983995171502771

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