{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:22:01Z","timestamp":1780467721249,"version":"3.54.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM122079"],"award-info":[{"award-number":["R01GM122079"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The danger posed by emerging infectious diseases necessitates the development of new tools that can mitigate the risk of animal pathogens spilling over into the human population. One promising approach is the development of recombinant viral vaccines that are transmissible, and thus capable of self-dissemination through hard to reach populations of wild animals. Indeed, mathematical models demonstrate that transmissible vaccines can greatly reduce the effort required to control the spread of zoonotic pathogens in their animal reservoirs, thereby limiting the chances of human infection. A key challenge facing these new vaccines, however, is the inevitability of evolutionary change resulting from their ability to self-replicate and generate extended chains of transmission. Further, carrying immunogenic transgenes is often costly, in terms of metabolic burden, increased competition with the pathogen, or due to unintended interactions with the viral host regulatory network. As a result, natural selection is expected to favor vaccine strains that down-regulate or delete these transgenes resulting in increased rates of transmission and reduced efficacy against the target pathogen. In addition, efficacy and evolutionary stability will often be at odds; as when longer, more efficacious antigens experience faster rates of evolutionary decay. Here, we ask how such trade-offs influence the overall performance of transmissible vaccines. We find that evolutionary instability can substantially reduce performance, even for vaccine candidates with the ideal combination of efficacy and transmission. However, we find that, at least in some cases, vaccine stability and overall performance can be improved by the inclusion of a second, redundant antigen. Overall, our results suggest that the successful application of recombinant transmissible vaccines will require consideration of evolutionary dynamics and epistatic effects, as well as basic measurements of epidemiological features.<\/jats:p>","DOI":"10.1093\/ve\/veab002","type":"journal-article","created":{"date-parts":[[2021,1,16]],"date-time":"2021-01-16T12:19:05Z","timestamp":1610799545000},"source":"Crossref","is-referenced-by-count":8,"title":["Designing transmissible viral vaccines for evolutionary robustness and maximum efficiency"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-6584","authenticated-orcid":false,"given":"Nathan C","family":"Layman","sequence":"first","affiliation":[{"name":"Department of Biological Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth M","family":"Tuschhoff","sequence":"additional","affiliation":[{"name":"Department of Mathematics, University of Idaho, 875 Perimeter Drive, Moscow, ID 83844, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott L","family":"Nuismer","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,1,25]]},"reference":[{"key":"2021030123552385100_veab002-B1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cels.2018.12.004","article-title":"Epistasis in a Fitness Landscape Defined by Antibody-Antigen Binding Free Energy","volume":"8","author":"Adams","year":"2019","journal-title":"Cell Systems"},{"key":"2021030123552385100_veab002-B2","author":"Antia","year":"2020"},{"key":"2021030123552385100_veab002-B3","doi-asserted-by":"crossref","first-page":"e0007251","DOI":"10.1371\/journal.pntd.0007251","article-title":"A Little Goes a Long Way: Weak Vaccine Transmission Facilitates Oral Vaccination Campaigns against Zoonotic Pathogens","volume":"13","author":"Basinski","year":"2018","journal-title":"PLoS Neglected Tropical Diseases"},{"key":"2021030123552385100_veab002-B4","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.vaccine.2017.12.037","article-title":"Evaluating the Promise of Recombinant Transmissible Vaccines","volume":"36","author":"Basinski","year":"2018","journal-title":"Vaccine"},{"key":"2021030123552385100_veab002-B5","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.3201\/eid2313.170544","article-title":"Zoonotic Disease Programs for Enhancing Global Health Security","volume":"23","author":"Belay","year":"2017","journal-title":"Emerging Infectious Diseases"},{"key":"2021030123552385100_veab002-B6","doi-asserted-by":"crossref","first-page":"e1006857","DOI":"10.1371\/journal.pcbi.1006857","article-title":"Recombinant Vector Vaccine Evolution","volume":"15","author":"Bull","year":"2019","journal-title":"PLoS Computational Biology"},{"key":"2021030123552385100_veab002-B7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.tim.2017.09.007","article-title":"Transmissible Viral Vaccines","volume":"26","author":"Bull","year":"2018","journal-title":"Trends in Microbiology"},{"key":"2021030123552385100_veab002-B8","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1128\/JVI.01532-15","article-title":"Sabin Vaccine Reversion in the Field: A Comprehensive Analysis of Sabin-Like Poliovirus Isolates in Nigeria","volume":"90","author":"Famulare","year":"2016","journal-title":"Journal of Virology"},{"key":"2021030123552385100_veab002-B9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/embor.2008.110","article-title":"Pricing Infectious Disease. 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