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Antibodies 2015, 4(4), 295-313; doi:10.3390/antib4040295

What Makes A Bacterial Oral Vaccine a Strong Inducer of High-Affinity IgA Responses?

and
†,*
ETH Zürich, Institute of Microbiology, Vladimir-Prelog-Weg 1-5/10, 8093 Zürich, Switzerland
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Dimiter S. Dimitrov
Received: 7 August 2015 / Revised: 15 September 2015 / Accepted: 8 October 2015 / Published: 15 October 2015
(This article belongs to the Special Issue SIgA in Mucosal Immunity)
View Full-Text   |   Download PDF [1140 KB, uploaded 15 October 2015]   |  

Abstract

Oral vaccination against bacterial pathogens that infect via the gastrointestinal tract is highly desirable for both economic reasons and the supposed benefits of local mucosal immunity. However, the majority of oral vaccine trials in humans result in failure. Here we try to assimilate our current knowledge to generate a model to improve vaccine development strategies. A model previously postulated describes the “immunogenicity” of intestinal bacterial species as a sum of the ability of the species to compete with the microbiota, the “pathogenicity index,” and the uniqueness of the species. While this model quite neatly explains the difficulties in generating appropriately attenuated live vaccine strains, it cannot explain the success of fully apathogenic or inactivated high-dose vaccines. We therefore propose a step away from focusing on bacterial traits, and towards the most basic requirements of mucosal vaccines: i.e., the delivery of antigen to the gut-associated lymphoid tissues and the ability of that antigen to induce germinal center formation. While the models seem trivial, both suggest that vaccination strategies permitting uncoupling of disease-causing phenomena from immune stimulation will have a much broader safety margin in a diverse human population. Our modified model further suggests the benefits of delivering antigen in the form of high-dose fully apathogenic or sterile particles, combined with relevant adjuvants. View Full-Text
Keywords: oral vaccine; high-affinity intestinal IgA; vaccination strategies; live-attenuation; adjuvant; gut-associated-lymphoid tissue oral vaccine; high-affinity intestinal IgA; vaccination strategies; live-attenuation; adjuvant; gut-associated-lymphoid tissue
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Moor, K.; Slack, E. What Makes A Bacterial Oral Vaccine a Strong Inducer of High-Affinity IgA Responses? Antibodies 2015, 4, 295-313.

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