Development and Evaluation of Novel Intranasal Vaccination Strategies to Prevent Porcine Reproductive and Respiratory Syndrome in Pigs
Başlık:
Development and Evaluation of Novel Intranasal Vaccination Strategies to Prevent Porcine Reproductive and Respiratory Syndrome in Pigs
Yazar:
Binjawadagi, Basavaraj, author.
ISBN:
9780438096363
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (180 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Committee members: Renukaradhya Gourapura.
Özet:
Porcine reproductive and respiratory syndrome (PRRS) is responsible for greater than $664 million direct annual loss to the US pork industry. The causative agent, PRRS virus (PRRSV), is an enveloped positive sense, single stranded RNA virus belongs to the family Arteriviridae. There are two genotypes, European (type I) and the North American (type II), with varying inter- and intra-genotypic genetic and antigenic diversity, signifying extreme mutagenic nature of the PRRSV. Though, since early 1990s both PRRS modified live virus (PRRS-MLV) and inactivated PRRSV vaccines are in use, control of PRRS remains unsuccessful. Moreover, PRRS-MLV has been implicated in the spread of vaccine origin variant virus to susceptible pigs. Available inactivated vaccines are safe but poorly immunogenic. Considering its safety advantage, development of a potent inactivated PRRSV vaccine is warranted. Intranasal delivery of vaccine is non-invasive and has the potential to stimulate a protective immune response not only in the respiratory tract, but also in the genital, gastric tracts. Additionally, efficient Th1 response inducing adjuvants are necessary in subunit/inactivated vaccines. Recently, we identified potent adjuvanticity of Mycobacterium tuberculosis whole cell lysate ( M. tb WCL) to PRRS-MLV. FDA approved and biodegradable PLGA (poly [lactide-co-glycolide]) based micro/nanoparticles are widely used for targeted/sustained delivery of drugs and vaccines. In this doctoral dissertation, we report two novel approaches of production of inactivated/multivalent subunit vaccines and their protective efficacy assessment in pigs. Recently, we have shown that single dose of PLGA nanoparticle (NPs) based inactivated PRRSV (NP-KAg) vaccine delivered intranasally to pigs, elicited immune response with partial viral clearance. Our hypothesis was that co-administration of NP-KAg vaccine twice with nanoparticle-entrapped/unentrapped M. tb WCL, intranasally, elicits robust anti-PRRSV cross-protective immunity with significant viral clearance in pigs. Our results demonstrated that, NP-KAg vaccine co-administered with unentrapped M. tb WCL completely cleared the detectable replicating infective challenged heterologous PRRSV strain MN184, both from the lungs and systemically. Further, assessment of various protective immune correlates supported the virus clearance results. Overall, our results confirmed that intranasal delivery of adjuvanted NP-KAg vaccine elicited broadly cross-protective immunity in pigs. Regarding our second approach, vaccine containing virus like particles (VLPs) can compensate many drawbacks of current inactivated and modified live virus vaccines. So far there are very few reports on development of PRRS-VLPs comprising of viral surface glycoproteins GP5 and M. However, the efficacy of those PRRS-VLPs vaccines was not evaluated in pigs. Thus, we adopted the following strategies: (i) produced PRRS-VLPs using the baculovirus expression system in insect (Sf9) cells, composed of viral surface proteins, GP5, GP4, GP3, GP2a and M; (ii) to reinforce immunogenicity of PRRS-VLPs, entrapped them in PLGA nanoparticles (NanoPRRS-VLPs); (iii) intranasally co-administered the NanoPRRS-VLPs or PRRS-VLPs with M. tb WCL. Our results indicated that both the formulations, NanoPRRS-VLPs and PRRS-VLPs, coupled with M. tb WCL significantly cleared the detectable infectious PRRSV and viral RNA load from the lungs and blood. Immunologically, enhanced PRRSV specific IgG antibody levels were observed. Both the approaches envisage the potential of these innovative vaccine formulations in preventing PRRS outbreaks in pigs.
Notlar:
School code: 0168
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