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Development and Evaluation of Nanoparticle-Based Intranasal Inactivated Influenza Virus Vaccine Candidates in Pigs
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Development and Evaluation of Nanoparticle-Based Intranasal Inactivated Influenza Virus Vaccine Candidates in Pigs. |
| 개인저자 | Dhakal, Santosh. |
| 단체저자명 | The Ohio State University. Comparative and Veterinary Medicine. |
| 발행사항 | [S.l.]: The Ohio State University., 2018. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2018. |
| 형태사항 | 236 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-05B. Dissertation Abstract International |
| ISBN | 9781687936219 |
| 학위논문주기 | Thesis (Ph.D.)--The Ohio State University, 2018. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
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| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | 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. |
| 일반주제명 | Nanotechnology. Virology. Immunology. Microbiology. |
| 언어 | 영어 |
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