In vivo and in vitro immune responses against Francisella tularensis vaccines are comparable among Fischer 344 rat substrains

Identifying suitable animal models and standardizing preclinical methods are important for the generation, characterization, and development of new vaccines, including those against Francisella tularensis. Non-human primates represent an important animal model to evaluate tularemia vaccine efficacy,...

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Main Authors: Roberto De Pascalis, Varunika Bhargava, Scott Espich, Terry H. Wu, H. Carl Gelhaus, Karen L. Elkins
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-07-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2023.1224480/full
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author Roberto De Pascalis
Varunika Bhargava
Scott Espich
Terry H. Wu
H. Carl Gelhaus
Karen L. Elkins
author_facet Roberto De Pascalis
Varunika Bhargava
Scott Espich
Terry H. Wu
H. Carl Gelhaus
Karen L. Elkins
author_sort Roberto De Pascalis
collection DOAJ
description Identifying suitable animal models and standardizing preclinical methods are important for the generation, characterization, and development of new vaccines, including those against Francisella tularensis. Non-human primates represent an important animal model to evaluate tularemia vaccine efficacy, and the use of correlates of vaccine-induced protection may facilitate bridging immune responses from non-human primates to people. However, among small animals, Fischer 344 rats represent a valuable resource for initial studies to evaluate immune responses, to identify correlates of protection, and to screen novel vaccines. In this study, we performed a comparative analysis of three Fischer rat substrains to determine potential differences in immune responses, to evaluate methods used to quantify potential correlates of protection, and to evaluate protection after vaccination. To this end, we took advantage of data previously generated using one of the rat substrains by evaluating two live vaccines, LVS and F. tularensis SchuS4-ΔclpB (ΔclpB). We compared immune responses after primary vaccination, adaptive immune responses upon re-stimulation of leukocytes in vitro, and sensitivity to aerosol challenge. Despite some detectable differences, the results highlight the similarity of immune responses to tularemia vaccines and challenge outcomes between the three substrains, indicating that all offer acceptable and comparable approaches as animal models to study Francisella infection and immunity.
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spelling doaj.art-4726494384c1437eadcf0523c2e454f52023-07-21T09:08:08ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-07-011410.3389/fmicb.2023.12244801224480In vivo and in vitro immune responses against Francisella tularensis vaccines are comparable among Fischer 344 rat substrainsRoberto De Pascalis0Varunika Bhargava1Scott Espich2Terry H. Wu3H. Carl Gelhaus4Karen L. Elkins5Laboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United StatesLaboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United StatesLaboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United StatesCenter for Infectious Disease and Immunity and Department of Internal Medicine, University of New Mexico, Albuquerque, NM, United StatesMRIGlobal, Kansas City, MO, United StatesLaboratory of Mucosal Pathogens and Cellular Immunology, Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United StatesIdentifying suitable animal models and standardizing preclinical methods are important for the generation, characterization, and development of new vaccines, including those against Francisella tularensis. Non-human primates represent an important animal model to evaluate tularemia vaccine efficacy, and the use of correlates of vaccine-induced protection may facilitate bridging immune responses from non-human primates to people. However, among small animals, Fischer 344 rats represent a valuable resource for initial studies to evaluate immune responses, to identify correlates of protection, and to screen novel vaccines. In this study, we performed a comparative analysis of three Fischer rat substrains to determine potential differences in immune responses, to evaluate methods used to quantify potential correlates of protection, and to evaluate protection after vaccination. To this end, we took advantage of data previously generated using one of the rat substrains by evaluating two live vaccines, LVS and F. tularensis SchuS4-ΔclpB (ΔclpB). We compared immune responses after primary vaccination, adaptive immune responses upon re-stimulation of leukocytes in vitro, and sensitivity to aerosol challenge. Despite some detectable differences, the results highlight the similarity of immune responses to tularemia vaccines and challenge outcomes between the three substrains, indicating that all offer acceptable and comparable approaches as animal models to study Francisella infection and immunity.https://www.frontiersin.org/articles/10.3389/fmicb.2023.1224480/fullFrancisella tularensistularemiaFischer 344 ratsintracellular bacteriavaccines
spellingShingle Roberto De Pascalis
Varunika Bhargava
Scott Espich
Terry H. Wu
H. Carl Gelhaus
Karen L. Elkins
In vivo and in vitro immune responses against Francisella tularensis vaccines are comparable among Fischer 344 rat substrains
Frontiers in Microbiology
Francisella tularensis
tularemia
Fischer 344 rats
intracellular bacteria
vaccines
title In vivo and in vitro immune responses against Francisella tularensis vaccines are comparable among Fischer 344 rat substrains
title_full In vivo and in vitro immune responses against Francisella tularensis vaccines are comparable among Fischer 344 rat substrains
title_fullStr In vivo and in vitro immune responses against Francisella tularensis vaccines are comparable among Fischer 344 rat substrains
title_full_unstemmed In vivo and in vitro immune responses against Francisella tularensis vaccines are comparable among Fischer 344 rat substrains
title_short In vivo and in vitro immune responses against Francisella tularensis vaccines are comparable among Fischer 344 rat substrains
title_sort in vivo and in vitro immune responses against francisella tularensis vaccines are comparable among fischer 344 rat substrains
topic Francisella tularensis
tularemia
Fischer 344 rats
intracellular bacteria
vaccines
url https://www.frontiersin.org/articles/10.3389/fmicb.2023.1224480/full
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