PLGA nanoparticle entrapped killed porcine reproductive and respiratory syndrome virus vaccine helps in viral clearance in pigs

Dwivedi, Varun; Manickam, Cordelia; Binjawadagi, Basavaraj; Renukaradhya, Gourapura J.

doi:10.1016/j.vetmic.2013.04.029

Cited by 39 publications

(38 citation statements)

References 55 publications

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“…It has been speculated that the efficacy of an inactivated vaccine is potentiallydetermined by the inactivation agent and/or the adjuvant [52–54]. In this study, the BEI-inactivated vaccine successfully induced the SN antibody response and partially inhibited viremia.…”

Section: Discussionmentioning

confidence: 71%

“…BEI has successfully been used to inactivate PRRSV in previous studies [52,57,58]. In these previous studies, inactivated PRRSV vaccine induced effective immune responses after single intranasal administrations [53,54]. However, the intranasal vaccine delivery route requires an additional vaccine spray machine and has to be performed by well-trained staff.…”

Section: Discussionmentioning

confidence: 99%

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Protective humoral immune response induced by an inactivated porcine reproductive and respiratory syndrome virus expressing the hypo-glycosylated glycoprotein 5

Lee¹,

Kwon²,

Osorio³

et al. 2014

Vaccine

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Porcine reproductive and respiratory syndrome (PRRS) causes significant economic losses to the swine industry worldwide. Although inactivated and live vaccines are commercially available for the control of PRRS, both types of vaccine have not always proven successful in terms of generating a protective immune response, particularly in the case of inactivated vaccines. In this study, we tested whether an inactivated vaccine could induce a humoral immune response to PRRS during a homologous challenge. Amino acid substitutions were introduced into glycoprotein (GP) 5 of the FL12 strain of the PRRS virus (PRRSV) using site-directed mutagenesis with a pFL12 infectious clone. The substitutions led to double deglycosylation in the putative glycosylation moieties on GP5. The mutant virus was subsequently inactivated with binary ethylenimine. The efficacy of the inactivated mutant virus was compared with that of the inactivated wild-type PRRSV. Only the inactivated mutant PRRSV induced serum neutralizing antibodies at six weeks post-vaccination. The group that was administered the inactivated mutant virus twice exhibited a significantly increased neutralizing antibody titer after a challenge with the virulent homologous strain and exhibited more rapid clearing of viremia compared to other groups, including the groups that were administered either the inactivated mutant or wild-type virus only once and the group that was administered the inactivated wild-type virus twice. Histopathological examination of lung tissue sections revealed that the group that was administered the inactivated mutant virus twice exhibited significantly thinner alveolar septa, whereas the thickness of the alveolar septa of the other groups were markedly increased due to lymphocyte infiltration. These results indicated that the deglycosylation of GP5 enhanced the immunogenicity of the inactivated mutant PRRSV and that twice administrations of the inactivated mutant virus conferred better protection against the homologous challenge. These findings suggest that the inactivated PRRSV that expresses a hypo-glycosylated GP5 is a potential inactivated vaccine candidate and a valuable tool for controlling PRRS for the swine industry.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Protective humoral immune response induced by an inactivated porcine reproductive and respiratory syndrome virus expressing the hypo-glycosylated glycoprotein 5

Lee¹,

Kwon²,

Osorio³

et al. 2014

Vaccine

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“…The phenotypes and frequencies of lymphoid and myeloid cells populations from 50,000 events of immunostained LMNCs were determined by flow cytometry as described previously. 23 For intracellular IFN-γ staining, Monensin (GolgiPlug, BD Biosciences) was added during the last 6 hours of the 48-hour incubation of LMNCs that were unstimulated or stimulated with PRRSV MN184 KAg as described above. LMNCs were first immunostained using pig lymphocyte-specific monoclonal antibodies (CD3ε, CD4α, CD8α, CD56, and TcR1N4) conjugated with different fluorochromes.…”

Section: Flow-cytometric Analysesmentioning

confidence: 99%

“…19 Previously, we have shown that a single dose of PRRSV KAg-entrapped in PLGA (50:50) nanoparticle (NP-KAg) elicits both mucosal and systemic immune responses. 22,23 Recently, NP-KAg coadministered intranasally twice with M. tb WCL induced cross-protective anti-PRRSV immune response in blood to a challenged heterologous PRRSV, associated with a significant reduction in viremia. 14 In this report, we made use of various types of the lung samples of that recent study 14 to evaluate viral load and local mucosal immunity both at airway surfaces and in the lung parenchyma, and also microscopic lung histopathology in vaccinated, heterologous PRRSV-challenged pigs.…”

Section: Introductionmentioning

confidence: 99%

“…PLGA is the food and drug administration (FDA)-approved agent, and PLGA-based intranasal delivery of PRRSV vaccine was found safe in pigs. 14,22,23 One of the strategies to augment uptake of particulate antigens by APCs is by increasing its surface hydrophilic nature of the particles by coating with a nonionic surfactant, Polaxamer 188. 54,55 Efficient Th1-immunity-inducing adjuvants are critical to promote a strong CMI response to subunit and inactivated virus vaccines.…”

mentioning

confidence: 99%

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An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination

Binjawadagi¹,

Dwivedi²,

Manickam³

et al. 2014

IJN

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Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating respiratory disease of pigs. The disease is caused by the PRRS virus (PRRSV), an Arterivirus which is a highly mutating RNA virus. Widely used modified live PRRSV vaccines have failed to prevent PRRS outbreaks and reinfections; moreover, safety of the live virus vaccines is questionable. Though poorly immunogenic, inactivated PRRSV vaccine is safe. The PRRSV infects primarily the lung macrophages. Therefore, we attempted to strengthen the immunogenicity of inactivated/killed PRRSV vaccine antigens (KAg), especially in the pig respiratory system, through: 1) entrapping the KAg in biodegradable poly(lactic-co-glycolic acid) nanoparticles (NP-KAg); 2) coupling the NP-KAg with a potent mucosal adjuvant, whole cell lysate of Mycobacterium tuberculosis (M. tb WCL); and 3) delivering the vaccine formulation twice intranasally to growing pigs. We have previously shown that a single dose of NP-KAg partially cleared the challenged heterologous PRRSV. Recently, we reported that NP-KAg coupled with unentrapped M. tb WCL significantly cleared the viremia of challenged heterologous PRRSV. Since PRRSV is primarily a lung disease, our goal in this study was to investigate lung viral load and various immune correlates of protection at the lung mucosal surfaces and its parenchyma in vaccinated heterologous PRRSV-challenged pigs. Our results indicated that out of five different vaccine-adjuvant formulations, the combination of NP-KAg and unentrapped M. tb WCL significantly cleared detectable replicating infective PRRSV with a tenfold reduction in viral RNA load in the lungs, associated with substantially reduced gross and microscopic lung pathology. Immunologically, strong humoral (enhanced virus neutralization titers by high avidity antibodies) and cell-mediated immune responses (augmented population of interferon-γ secreting CD4+ and CD8+ lymphocytes and reduced secretion of immunosuppressive cytokines) in the lungs were observed. In conclusion, combination of NP-KAg and soluble M. tb WCL elicits broadly cross-protective anti-PRRSV immunity in the pig respiratory system.

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Adsorption of a porcine reproductive and respiratory syndrome virus DNA vaccine candidate onto biodegradable nanoparticles improves immunogenicity in mice

et al. 2015

Arch Virol

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Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating viral disease of pigs. Safer and more effective vaccines are urgently needed. In this study, a synthetic ORF5 gene of porcine reproductive and respiratory syndrome virus (PRRSV) was adsorbed onto poly(D, L-lactide-co-glycolide)/polyethylenimine (PLGA/PEI) nanoparticles. We prepared a PLGA-nanoparticle-adsorbed PRRSV DNA vaccine and a PEI-DNA complex. The results showed that these model vaccines could significantly enhance humoral and cellular immune responses when compared with the responses induced by pcDNA3.1-SynORF5, a plasmid construct for expression of PRRSV ORF5. PLGA-branched PEI nanoparticles induced the most efficient immune response. The delivery system and adjuvant provide new models for the development of vaccines against PRRSV.

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PLGA nanoparticle entrapped killed porcine reproductive and respiratory syndrome virus vaccine helps in viral clearance in pigs

Cited by 39 publications

References 55 publications

Protective humoral immune response induced by an inactivated porcine reproductive and respiratory syndrome virus expressing the hypo-glycosylated glycoprotein 5

Protective humoral immune response induced by an inactivated porcine reproductive and respiratory syndrome virus expressing the hypo-glycosylated glycoprotein 5

An innovative approach to induce cross-protective immunity against porcine reproductive and respiratory syndrome virus in the lungs of pigs through adjuvanted nanotechnology-based vaccination

Adsorption of a porcine reproductive and respiratory syndrome virus DNA vaccine candidate onto biodegradable nanoparticles improves immunogenicity in mice

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