Efficacy of an Inactivated PRRSV Vaccine: Induction of Virus-Neutralizing Antibodies and Partial Virological Protection upon Challenge

Misinzo, Gerald; Delputte, Peter; Meerts, Peter; Drexler, Christa; Nauwynck, Hans

doi:10.1007/978-0-387-33012-9_81

Cited by 13 publications

(14 citation statements)

References 18 publications

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“…A comparative study of MLV and KV vaccines in boars showed that while vaccination with an MLV vaccine decreased viremia and virus shedding in semen, vaccination with a KV vaccine did not change onset, duration or level of viremia, or virus shedding in semen [47]. Preliminary experiments in our lab showed that while an experimental inactivated PRRSV vaccine was able to induce neutralizing antibodies, it could only partly block viremia after challenge [41]. The current incomplete protection of KV vaccines against PRRSV infection might be caused by an over-inactivation of the virus, resulting in destruction of neutralizing viral epitopes.…”

Section: Introductionmentioning

confidence: 86%

Assessing the functionality of viral entry-associated domains of porcine reproductive and respiratory syndrome virus during inactivation procedures, a potential tool to optimize inactivated vaccines

2009

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-Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe economic losses in the pig industry worldwide. Currently, vaccines based on inactivated PRRSV provide limited protection of pigs against infection, most likely because viral epitopes associated with the induction of neutralizing antibodies are not or poorly conserved during inactivation. To analyze the effect of inactivation procedures on the interaction of PRRSV with receptors involved in virus entry, a new assay was set up in this study. Viral entry-associated domains are most likely important for the induction of neutralizing antibodies, since neutralizing antibodies block interaction of PRRSV with cellular receptors. To investigate the interaction of PRRSV with the cellular receptors upon different inactivation procedures, attachment to and internalization of inactivated PRRSV into macrophages were monitored. AT-2 could not inactivate PRRSV completely and is therefore not useful for vaccine development. PRRSV inactivated with ultraviolet light, binary ethyleneimine and gamma irradiation, which all mainly have an effect at the genomic level, showed no difference compared to control live virus at all levels of virus entry, whereas PRRSV treated with formaldehyde, glutaraldehyde and pH changes, which all have a modifying effect on proteins, was not able to internalize into macrophages anymore. These results suggest that inactivation with methods with a main effect on the viral genome preserve PRRSV entry-associated domains and are useful for future development of an effective inactivated vaccine against PRRSV. Although PRRSV incubation at 37°C can completely inactivate PRRSV with preservation of entry-associated domains, this method is not recommended for vaccine development, since the mechanism is yet unknown.PRRSV / inactivation / vaccine / entry-associated domain / sialoadhesin

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Section: Introductionmentioning

confidence: 86%

Assessing the functionality of viral entry-associated domains of porcine reproductive and respiratory syndrome virus during inactivation procedures, a potential tool to optimize inactivated vaccines

2009

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“…The commercially available PRRS inactivated vaccine does not induce a sufficient immune response and does not adequately protect pigs from viremia when challenged with PRRSVs [11–13]. Although previous studies have shown that PRRS inactivated vaccines are able to inhibit viral shedding and induce neutralizing antibodies, these results vary depending on the virus strain and the type of tissue culture used to produce the vaccines [11,14]. Numerous efforts have been made to develop an ideal PRRS inactivated vaccine that would offer broad protection and high immunogenicity [15,16], but these efforts have been unsuccessful.…”

Section: Introductionmentioning

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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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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“…Besides, there are major concerns about the safety of attenuated PRRSV vaccines, as the vaccine virus on itself can cause viremia and can spread transplacentally and horizontally with the risk of reverting to virulence [2,18,22]. Inactivated vaccines on the other hand are safe and it has been shown by Misinzo et al that it is possible to stimulate the VN antibody response in naïve piglets by immunization with inactivated PRRSV [16]. Commercially available inactivated PRRSV vaccines however do not induce VN antibodies and do not sufficiently protect against viremia [19,24,35].…”

Section: Introductionmentioning

confidence: 99%

Development of an experimental inactivated PRRSV vaccine that induces virus-neutralizing antibodies

et al. 2009

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-Porcine reproductive and respiratory syndrome virus (PRRSV) can induce reproductive disorders and is involved in the porcine respiratory disease complex, causing tremendous economic losses to the swine industry. Inactivated PRRSV vaccines are preferred over attenuated vaccines because of their safety and flexibility towards emerging virus strains, but the efficacy of current inactivated PRRSV vaccines is questionable. In this study, experimental inactivated PRRSV vaccines were developed, based on two formerly optimized inactivation procedures: UV irradiation and treatment with binary ethylenimine (BEI). In a first experiment, it was shown that vaccination with UV-or BEI-inactivated virus in combination with Incomplete Freund's Adjuvant induced virus-specific antibodies and strongly primed the virus-neutralizing (VN) antibody response. Subsequently, the influence of adjuvants on the immunogenicity of neutralizing epitopes on the inactivated virus was investigated. It was shown that vaccination with BEI-inactivated virus in combination with a commercial oil-in-water adjuvant induced high titers (3.4 log 2 ) of VN antibodies in 6/6 pigs, instead of only priming the neutralizing antibody response. After challenge, neutralizing antibody titers in these vaccinated animals rose to a mean value of 5.5 log 2 , and the duration of the viremia was reduced to an average of 1 week. This study shows that, by the use of an optimized inactivation procedure and a suitable adjuvant, inactivated PRRSV vaccines can be developed that induce VN antibodies and offer partial protection upon challenge.

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Efficacy of an Inactivated PRRSV Vaccine: Induction of Virus-Neutralizing Antibodies and Partial Virological Protection upon Challenge

Cited by 13 publications

References 18 publications

Assessing the functionality of viral entry-associated domains of porcine reproductive and respiratory syndrome virus during inactivation procedures, a potential tool to optimize inactivated vaccines

Assessing the functionality of viral entry-associated domains of porcine reproductive and respiratory syndrome virus during inactivation procedures, a potential tool to optimize inactivated vaccines

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

Development of an experimental inactivated PRRSV vaccine that induces virus-neutralizing antibodies

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