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008200131s2018 ||||||||||||||||| ||eng d
020 ▼a 9781687936219
035 ▼a (MiAaPQ)AAI27539076
035 ▼a (MiAaPQ)OhioLINKosu1529829066502348
040 ▼a MiAaPQ ▼c MiAaPQ ▼d 247004
0820 ▼a 576
1001 ▼a Dhakal, Santosh.
24510 ▼a Development and Evaluation of Nanoparticle-Based Intranasal Inactivated Influenza Virus Vaccine Candidates in Pigs.
260 ▼a [S.l.]: ▼b The Ohio State University., ▼c 2018.
260 1 ▼a Ann Arbor: ▼b ProQuest Dissertations & Theses, ▼c 2018.
300 ▼a 236 p.
500 ▼a Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
5021 ▼a Thesis (Ph.D.)--The Ohio State University, 2018.
506 ▼a This item must not be sold to any third party vendors.
520 ▼a Swine influenza A virus (SwIAV) causes severe economic loss to the swine industry globally. Pigs are also regarded as mixing vessel for influenza A viruses (IAV) of human, avian and swine origin, generating viruses capable of human infections. Vaccination is one of the effective means to prevent influenza in pigs. Currently available SwIAV vaccines in pigs are predominantly monovalent or multivalent whole inactivated virus (WIV) vaccines administered by intramuscular (IM) route with potent adjuvants. IM WIV vaccines provide homologous protection, but limited heterologous protection against continuously evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. Additionally, IM WIV vaccines are not effective in the presence of maternally-derived antibodies (MDA) and often lead to vaccine-associated enhanced respiratory disease (VAERD) when vaccine virus antigenically mismatches with challenge virus. Therefore, an alternative vaccine delivery approach is required to develop efficient SwIAV vaccine. A novel vaccine delivery platform using biodegradable and biocompatible polymer-based nanoparticles (NPs) administered through intranasal (IN) route, has the potential to elicit strong mucosal and cellular immune responses in pigs and overcome the limitations of current IM WIV vaccines.In this study, we developed poly(lactic-co-glycolic acid) (PLGA), polyanhydride, chitosan and Nano-11 NPs-based SwIAV vaccine candidates. Inactivated/killed SwIAV H1N2 (delta-lineage) antigens (KAg) were either encapsulated within or adhered onto the surface of NPs. The vaccine candidates were administered twice IN as mist to nursery pigs. Vaccinates and controls were then challenged with a zoonotic and virulent heterologous SwIAV H1N1 (gamma-lineage) via IN and intratracheal routes. None of the nanovaccines enhanced respiratory disease after virus infection. The IN PLGA-based nanovaccine resulted in robust cross-reactive cell-mediated immunity, protected pigs from fever and cleared infectious virus from lungs but not from the nasal cavity, probably due to its inability to improve mucosal antibody response. Polyanhydride NPs-based influenza nanovaccine also enhanced cell-mediated immune response, protected pigs from fever and lowered infectious virus from nasal swabs 6 to 8 times. In another study, mucoadhesive chitosan NPs-based influenza nanovaccine exhibited an enhanced mucosal, humoral and cellular immune responses and lowered infectious challenge virus both from nasal cavity and lungs. We also showed the adjuvant potential of corn-derived Nano-11 NPs in pigs after IN administration with influenza KAg which can be a safe, potent and cost-effective adjuvant for mucosal immunizations. In summary, diverse immunogenic properties of these NPs can be used for improving the breadth of protective efficacy of mucosal swine influenza vaccines. Future studies should explore the combinatorial potential of these IN nanovaccine candidates, evaluate their ability to override MDA effect and compare the vaccine efficacy with commercial vaccines against SwIAV challenge with antigenic variant.
590 ▼a School code: 0168.
650 4 ▼a Nanotechnology.
650 4 ▼a Virology.
650 4 ▼a Immunology.
650 4 ▼a Microbiology.
690 ▼a 0652
690 ▼a 0720
690 ▼a 0982
690 ▼a 0410
71020 ▼a The Ohio State University. ▼b Comparative and Veterinary Medicine.
7730 ▼t Dissertations Abstracts International ▼g 81-05B.
773 ▼t Dissertation Abstract International
790 ▼a 0168
791 ▼a Ph.D.
792 ▼a 2018
793 ▼a English
85640 ▼u http://www.riss.kr/pdu/ddodLink.do?id=T15494323 ▼n KERIS ▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다.
980 ▼a 202002 ▼f 2020
990 ▼a ***1008102
991 ▼a E-BOOK