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

Authors

John P. Bannantine, USDA-ARSFollow
Murray E. Hines II, University of Georgia
Luiz E. Bermudez, Oregon State University
Adel M. Talaat, University of Wisconsin - Madison & Cairo UniversityFollow
Srinand Sreevatsan, University of Minnesota- MinneapolisFollow
Judith R. Stabel, USDA-ARS
Yung-Fu Chang, Cornell University
Paul M. Coussens, Michigan State University
Raúl G. Barletta, University of Nebraska - LincolnFollow
William C. Davis, Washington State University
Desmond M. Collins, Washington State University
Yrjö T. Gröhn, Cornell University
Vivek Kapur, USDA-ARSFollow

Date of this Version

9-9-2014

Citation

Frontiers in Cellular and Infection Microbiology www.frontiersin.org September 2014|Volume 4|Article 126 | 1/11

Comments

2014 Bannantine, Hines, Bermudez, Talaat, Sreevatsan, Stabel, Chang, Coussens, Barletta, Davis, Collins, Gröhn and Kapur.

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 inactived 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 transcriptional mutation of virulence and metablolic genes in MAP. In order to accelerate the process of identification and comparative elvaluation of he 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 established 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 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 animals 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.