Record Details

A rational framework for evaluating the next generation of vaccines against Mycobacterium avium subspecies paratuberculosis

ScholarsArchive at Oregon State University

Field Value
Title A rational framework for evaluating the next generation of vaccines against Mycobacterium avium subspecies paratuberculosis
Names Bannantine, John P. (creator)
Hines, Murray E., II (creator)
Bermudez, Luiz E. (creator)
et al. (creator)
Date Issued 2014-09-09 (iso8601)
Note To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work. This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Frontiers Research Foundation. The published article can be found at: http://www.frontiersin.org/Cellular_and_Infection_Microbiology.
Abstract Since the early 1980s, several investigations have focused on developing a vaccine against
Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne’s
disease in cattle and sheep. These studies used whole-cell inactivated vaccines that
have proven useful in limiting disease progression, but have not prevented infection.
In contrast, modified live vaccines that invoke a Th1 type immune response, may
improve protection against infection. Spurred by recent advances in the ability to create
defined knockouts in MAP, several independent laboratories have developed modified live
vaccine candidates by transpositional mutation of virulence and metabolic genes in MAP.
In order to accelerate the process of identification and comparative evaluation of the
most promising modified live MAP vaccine candidates, members of a multi-institutional
USDA-funded research consortium, the Johne’s disease integrated program (JDIP), met
to establish a standardized testing platform using agreed upon protocols. A total of 22
candidates vaccine strains developed in five independent laboratories in the United States
and New Zealand voluntarily entered into a double blind stage gated trial pipeline. In Phase
I, the survival characteristics of each candidate were determined in bovine macrophages.
Attenuated strains moved to Phase II, where tissue colonization of C57/BL6 mice were
evaluated in a challenge model. In Phase III, five promising candidates from Phase I
and II were evaluated for their ability to reduce fecal shedding, tissue colonization and
pathology in a baby goat challenge model. Formation of a multi-institutional consortium for
vaccine strain evaluation has revealed insights for the implementation of vaccine trials for
Johne’s disease and other animal pathogens. We conclude by suggesting the best way
forward based on this 3-phase trial experience and challenge the rationale for use of a
macrophage-to-mouse-to native host pipeline for MAP vaccine development.
Genre Article
Access Condition http://creativecommons.org/licenses/by/3.0/us/
Topic Johne’s disease
Identifier Bannantine, J. P., Hines, M. E., II, Bermudez, L. E., Talaat, A. M., Sreevatsan, S., Stabel, J. R., ... & Kapur, V. (2014). A rational framework for evaluating the next generation of vaccines against Mycobacterium avium subspecies paratuberculosis. Frontiers in Cellular and Infection Microbiology, 4, 126. doi:10.3389/fcimb.2014.00126

© Western Waters Digital Library - GWLA member projects - Designed by the J. Willard Marriott Library - Hosted by Oregon State University Libraries and Press