Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


osu1249332969.pdf (1.39 MB)

ETD Abstract Container

Abstract Header

STUDY TOWARD THE DEVELOPMENT OF ADVANCED INFLUENZA VACCINES

Wang, Leyi
http://rave.ohiolink.edu/etdc/view?acc_num=osu1249332969

Abstract Details

2009, Doctor of Philosophy, Ohio State University, Veterinary Preventive Medicine.
In this study, several strategies have been explored for the development of live attenuated and killed DIVA influenza vaccines. The NS1 protein of influenza A viruses, a virulence marker, is a good target to attenuate viruses in developing a live attenuated vaccine. Through passage in eggs, we found that several different NS1 truncation variants were generated from a parental non-stable virus strain, A/turkey/Oregon/71-delNS1 (H7N3). Based on the results from both in vitro and in vivo studies, naturally selected NS1 truncation variants are potentially live attenuated influenza vaccine candidates in poultry. With a large deletion in NS genes, those NS1 truncation variants have a low possibility to revert back to virulent viruses. We then checked feasibility of those NS1 truncation variants to be used for in ovo vaccination, and hatchability of vaccinated groups was significantly lower than that of PBS control group, indicating that NS1 truncation variants were not attenuated enough to be used for in ovo vaccination and there was a need for further attenuation. To improve hatchability of NS1 truncation variant vaccinated eggs, temperature sensitive (ts) mutation and HA substitution strategies were utilized. NS1 truncation variants containing ts mutations exhibited ts phenotype in vitro, but were not attenuated enough to improve hatchability of in ovo vaccination. We showed that HA substitution had different effect on hatchability of in ovo vaccination, and the hatchability of eggs inoculated with NS1 truncation variants of different HA subtypes was still significantly lower than PBS control group. Therefore, we explored a strategy of targeting non-conserved parts of non-coding regions (NCR) to attenuate NS1 truncation variant viruses. In vitro studies illustrated that even single nucleotide change in NCR of PA or PB1 segments could affect protein expression. In addition, it was found that mutations in NCR of PA segment alone or PA and PB1 combination affect virus replication. With more understanding of the role of NCR in virus replication cycle, we speculate targeting non-conserved parts of NCR to further attenuate NS1 truncation variants is feasible. Further study is needed to introduce those mutations involved in decreased virus replication into NS1 truncation variants for further attenuation. In the case of development of killed DIVA avian influenza vaccines, two strategies, NS1 protein and heterologous NA, were utilized to generate DIVA vaccines. In vivo study showed that both kinds of DIVA vaccines significantly reduced challenge virus shedding in the oviduct of breeder turkeys as well as trachea and cloaca of young and breeder turkeys compared to the non-vaccinated control group, which suggests proper vaccination could effectively prevent egg production drop and potential viral contamination of eggs in infected turkeys. In combination with DIVA serological tests, we expect the developed vaccines will be useful to control turkey H3N2 influenza.
Chang-Won Lee (Committee Chair)
Y Saif (Committee Member)
Daral Jackwood (Committee Member)
Jeffrey LeJeune (Committee Member)
188 p.
Virology
Avian Influenza; NS1 truncation variants; temperature sensitive; mutations; non-coding region; live attenuated vaccine; inactivated vaccine

Recommended Citations

Citations

  • Wang, L. (2009). STUDY TOWARD THE DEVELOPMENT OF ADVANCED INFLUENZA VACCINES [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1249332969

    APA Style (7th edition)

  • Wang, Leyi. STUDY TOWARD THE DEVELOPMENT OF ADVANCED INFLUENZA VACCINES. 2009. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1249332969.

    MLA Style (8th edition)

  • Wang, Leyi. "STUDY TOWARD THE DEVELOPMENT OF ADVANCED INFLUENZA VACCINES." Doctoral dissertation, Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1249332969

    Chicago Manual of Style (17th edition)

osu1249332969
1,186
© 2009, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.