Evaluation of Immune Nanoparticles for Rapid and Non-Specific Activation of Antiviral and Antibacterial Immune Responses in Cattle, Swine, and Poultry

Given the rapid potential spread of agricultural pathogens, and the lack of vaccines for many, there is an important unmet need for strategies to induce rapid and non-specific immunity against these viral and bacterial threats. One approach to the problem is to generate non-specific immune responses...

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Main Authors: William H. Wheat, Lyndah Chow, Alyssa M. Betlach, Maria Pieters, Jade Kurihara, Cooper Dow, Valerie Johnson, Franklyn B. Garry, Steven Dow
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Animals
Subjects:
Online Access:https://www.mdpi.com/2076-2615/13/10/1686
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author William H. Wheat
Lyndah Chow
Alyssa M. Betlach
Maria Pieters
Jade Kurihara
Cooper Dow
Valerie Johnson
Franklyn B. Garry
Steven Dow
author_facet William H. Wheat
Lyndah Chow
Alyssa M. Betlach
Maria Pieters
Jade Kurihara
Cooper Dow
Valerie Johnson
Franklyn B. Garry
Steven Dow
author_sort William H. Wheat
collection DOAJ
description Given the rapid potential spread of agricultural pathogens, and the lack of vaccines for many, there is an important unmet need for strategies to induce rapid and non-specific immunity against these viral and bacterial threats. One approach to the problem is to generate non-specific immune responses at mucosal surfaces to rapidly protect from entry and replication of both viral and bacterial pathogens. Using complexes of charged nanoparticle liposomes with both antiviral and antibacterial toll-like receptor (TLR) nucleic acid ligands (termed liposome-TLR complexes or <i>LTC</i>), we have previously demonstrated considerable induction of innate immune responses in nasal and oropharyngeal tissues and protection from viral and bacterial pathogens in mixed challenge studies in rodents, cattle, and companion animals. Therefore, in the present study, we used in vitro assays to evaluate the ability of the LTC immune stimulant to activate key innate immune pathways, particularly interferon pathways, in cattle, swine, and poultry. We found that LTC complexes induced strong production of type I interferons (IFNα and IFNβ) in both macrophages and leukocyte cultures from all three species. In addition, the LTC complexes induced the production of additional key protective cytokines (IL-6, IFNγ, and TNFα) in macrophages and leukocytes in cattle and poultry. These findings indicate that the LTC mucosal immunotherapeutic has the capability to activate key innate immune defenses in three major agricultural species and potentially induce broad protective immunity against both viral and bacterial pathogens. Additional animal challenge studies are warranted to evaluate the protective potential of LTC immunotherapy in cattle, swine, and poultry.
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spelling doaj.art-e125262b6b2644dfb60c4463599185302023-11-18T00:10:49ZengMDPI AGAnimals2076-26152023-05-011310168610.3390/ani13101686Evaluation of Immune Nanoparticles for Rapid and Non-Specific Activation of Antiviral and Antibacterial Immune Responses in Cattle, Swine, and PoultryWilliam H. Wheat0Lyndah Chow1Alyssa M. Betlach2Maria Pieters3Jade Kurihara4Cooper Dow5Valerie Johnson6Franklyn B. Garry7Steven Dow8Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USADepartment of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USASwine Veterinary Center, St. Peter, MN 56082, USADepartment of Veterinary Population Medicine, Veterinary Diagnostic Laboratory and Swine Disease Eradication Center, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55455, USADepartment of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USAIdaho State University, Pocatello, ID 83209, USACollege of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USADepartment of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USADepartment of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USAGiven the rapid potential spread of agricultural pathogens, and the lack of vaccines for many, there is an important unmet need for strategies to induce rapid and non-specific immunity against these viral and bacterial threats. One approach to the problem is to generate non-specific immune responses at mucosal surfaces to rapidly protect from entry and replication of both viral and bacterial pathogens. Using complexes of charged nanoparticle liposomes with both antiviral and antibacterial toll-like receptor (TLR) nucleic acid ligands (termed liposome-TLR complexes or <i>LTC</i>), we have previously demonstrated considerable induction of innate immune responses in nasal and oropharyngeal tissues and protection from viral and bacterial pathogens in mixed challenge studies in rodents, cattle, and companion animals. Therefore, in the present study, we used in vitro assays to evaluate the ability of the LTC immune stimulant to activate key innate immune pathways, particularly interferon pathways, in cattle, swine, and poultry. We found that LTC complexes induced strong production of type I interferons (IFNα and IFNβ) in both macrophages and leukocyte cultures from all three species. In addition, the LTC complexes induced the production of additional key protective cytokines (IL-6, IFNγ, and TNFα) in macrophages and leukocytes in cattle and poultry. These findings indicate that the LTC mucosal immunotherapeutic has the capability to activate key innate immune defenses in three major agricultural species and potentially induce broad protective immunity against both viral and bacterial pathogens. Additional animal challenge studies are warranted to evaluate the protective potential of LTC immunotherapy in cattle, swine, and poultry.https://www.mdpi.com/2076-2615/13/10/1686agricultureimmunotherapycytokinesinnate immunitypandemiccountermeasures
spellingShingle William H. Wheat
Lyndah Chow
Alyssa M. Betlach
Maria Pieters
Jade Kurihara
Cooper Dow
Valerie Johnson
Franklyn B. Garry
Steven Dow
Evaluation of Immune Nanoparticles for Rapid and Non-Specific Activation of Antiviral and Antibacterial Immune Responses in Cattle, Swine, and Poultry
Animals
agriculture
immunotherapy
cytokines
innate immunity
pandemic
countermeasures
title Evaluation of Immune Nanoparticles for Rapid and Non-Specific Activation of Antiviral and Antibacterial Immune Responses in Cattle, Swine, and Poultry
title_full Evaluation of Immune Nanoparticles for Rapid and Non-Specific Activation of Antiviral and Antibacterial Immune Responses in Cattle, Swine, and Poultry
title_fullStr Evaluation of Immune Nanoparticles for Rapid and Non-Specific Activation of Antiviral and Antibacterial Immune Responses in Cattle, Swine, and Poultry
title_full_unstemmed Evaluation of Immune Nanoparticles for Rapid and Non-Specific Activation of Antiviral and Antibacterial Immune Responses in Cattle, Swine, and Poultry
title_short Evaluation of Immune Nanoparticles for Rapid and Non-Specific Activation of Antiviral and Antibacterial Immune Responses in Cattle, Swine, and Poultry
title_sort evaluation of immune nanoparticles for rapid and non specific activation of antiviral and antibacterial immune responses in cattle swine and poultry
topic agriculture
immunotherapy
cytokines
innate immunity
pandemic
countermeasures
url https://www.mdpi.com/2076-2615/13/10/1686
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