Gaps in Human Immunity Against Swine Origin Influenza A Viruses and the Use of Swine Vaccination to Reduce Public Health Threat

Gaps in Human Immunity Against Swine Origin Influenza A Viruses and the Use of Swine Vaccination to Reduce Public Health Threat

Bibliographic Details
Main Author: Lorbach, Joshua
Language:English
Published: The Ohio State University / OhioLINK 2020
Subjects:
Immunology
Livestock
Public Health
Virology
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1587727549815743
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu15877275498157432021-08-03T07:14:39Z Gaps in Human Immunity Against Swine Origin Influenza A Viruses and the Use of Swine Vaccination to Reduce Public Health Threat Lorbach, Joshua Immunology Livestock Public Health Virology Interspecies influenza A virus (IAV) transmission is a fundamental mechanism fueling emergence of novel IAVs with significant impact on human health. Prolonged contact between humans and pigs at agricultural exhibitions permits bidirectional transmission of IAV with sporadic cases of zoonotic infections in people. IAVs introduced from people to swine populations persist in this animal reservoir while human population immunity changes significantly over time. Since all previous pandemic IAVs originated in animals, characterizing existing human immunity against the increasingly diverse IAVs circulating in swine (IAV-S) and investigating approaches to mitigate the risk posed by IAV-S are important to protect public health. The second chapter of this dissertation details the results of a study of serologic immunity against contemporary IAV-S in 153 healthy human subjects donors. We analyzed samples by hemagglutination-inhibition (HAI) assay against a panel of viruses including referent human seasonal IAVs. Results indicate gaps in human immunity exist at the population level and within individual age groups for H1 and H3 IAVs circulating in US swine. Youth appear particularly predisposed to infection with several examined viruses. Expansion of current gaps could eventually permit sustained transmission of human-adapted IAV-S following spillover to people. The third chapter describes a study comparing the effect of IAV vaccination in swine on post-challenge viral shedding and transmission to exposed ferrets acting as surrogates for humans. Vaccination with killed or live-attenuated influenza vaccine reduced virus shedding in pigs following intranasal IAV challenge, and virus transmission was delayed for ferrets exposed to pigs that had received the live-attenuated influenza vaccine. These results indicate pre-exhibition influenza vaccination of swine could reduce the public health risk posed by IAV-S. The fourth chapter discusses preliminary work investigating use of humanized mouse models incorporating existing (memory) human immunity to advance current IAV pandemic risk assessment approaches. Challenge of humanized mice using minimally-passaged IAV strains would be most informative for such investigations, Though it has historically been considered necessary to species-adapt IAV for infection of mice, findings overall support the ability of non-mouse-adapted human and swine IAV isolates to cause disease in immunocompromised NSG mice. However, differences observed in clinical signs and tissue virus titers between H1 and H3 IAV subtype IAVs used for challenge of control mice indicate serial passage may be necessary for certain IAV isolates to achieve desired disease phenotype. Serology has identified significant gaps in protective immunity against multiple contemporary swine-origin influenza A viruses likely to result in continued zoonotic transmission at the human-animal interface. This project has also investigated the use of swine vaccination to effectively control intra- and interspecies transmission of IAV at interfaces with human-pig contact. Continuing to advance the understanding of anti-IAV immunity in the human population and exploring additional risk mitigation strategies is necessary to further reduce public health risk posed by at the swine-human interface. 2020-10-12 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1587727549815743 http://rave.ohiolink.edu/etdc/view?acc_num=osu1587727549815743 restricted--full text unavailable until 2025-05-13 This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic Immunology
Livestock
Public Health
Virology
spellingShingle Immunology
Livestock
Public Health
Virology
Lorbach, Joshua
Gaps in Human Immunity Against Swine Origin Influenza A Viruses and the Use of Swine Vaccination to Reduce Public Health Threat
author Lorbach, Joshua
author_facet Lorbach, Joshua
author_sort Lorbach, Joshua
title Gaps in Human Immunity Against Swine Origin Influenza A Viruses and the Use of Swine Vaccination to Reduce Public Health Threat
title_short Gaps in Human Immunity Against Swine Origin Influenza A Viruses and the Use of Swine Vaccination to Reduce Public Health Threat
title_full Gaps in Human Immunity Against Swine Origin Influenza A Viruses and the Use of Swine Vaccination to Reduce Public Health Threat
title_fullStr Gaps in Human Immunity Against Swine Origin Influenza A Viruses and the Use of Swine Vaccination to Reduce Public Health Threat
title_full_unstemmed Gaps in Human Immunity Against Swine Origin Influenza A Viruses and the Use of Swine Vaccination to Reduce Public Health Threat
title_sort gaps in human immunity against swine origin influenza a viruses and the use of swine vaccination to reduce public health threat
publisher The Ohio State University / OhioLINK
publishDate 2020
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1587727549815743
work_keys_str_mv AT lorbachjoshua gapsinhumanimmunityagainstswineorigininfluenzaavirusesandtheuseofswinevaccinationtoreducepublichealththreat
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