Variations in antibody repertoires correlate with vaccine responses
- Yana Safonova1,2,3,
- Sung Bong Shin4,
- Luke Kramer5,
- James Reecy5,
- Corey T. Watson2,
- Timothy P.L. Smith4 and
- Pavel A. Pevzner1
- 1Computer Science and Engineering Department, University of California at San Diego, San Diego, California 92093, USA;
- 2Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA;
- 3Department of Computer Science, Johns Hopkins University, Baltimore, Maryland 21218, USA;
- 4U.S. Meat Animal Research Center, USDA-ARS, Clay Center, Nebraska 68933, USA;
- 5Department of Animal Science, Iowa State University, Ames, Iowa 50011, USA
Abstract
An important challenge in vaccine development is to figure out why a vaccine succeeds in some individuals and fails in others. Although antibody repertoires hold the key to answering this question, there have been very few personalized immunogenomics studies so far aimed at revealing how variations in immunoglobulin genes affect a vaccine response. We conducted an immunosequencing study of 204 calves vaccinated against bovine respiratory disease (BRD) with the goal to reveal variations in immunoglobulin genes and somatic hypermutations that impact the efficacy of vaccine response. Our study represents the largest longitudinal personalized immunogenomics study reported to date across all species, including humans. To analyze the generated data set, we developed an algorithm for identifying variations of the immunoglobulin genes (as well as frequent somatic hypermutations) that affect various features of the antibody repertoire and titers of neutralizing antibodies. In contrast to relatively short human antibodies, cattle have a large fraction of ultralong antibodies that have opened new therapeutic opportunities. Our study reveals that ultralong antibodies are a key component of the immune response against the costliest disease of beef cattle in North America. The detected variants of the cattle immunoglobulin genes, which are implicated in the success/failure of the BRD vaccine, have the potential to direct the selection of individual cattle for ongoing breeding programs.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.276027.121.
- Received July 25, 2021.
- Accepted February 28, 2022.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
