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

Abstract

-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.

Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges

“…Also, virus-specific antibodies could be induced against BEI-inactivated Nipah virus; however, these did not neutralizing the virus in vitro [78]. After vaccination of pigs with BEI-inactivated PRRSV, they induced a virus-specific and virus-neutralize antibody response, which was able to reduce viremia after challenge [79]. However, rainbow trout vaccinated with BEI-inactivated HNV and challenged with live HNV showed no statistically significant differences between the cumulative percentage mortality in the group of fish immunized with the BEI vaccines and the mortality of fish in the mock-vaccinated control groups when tested 28 or 56 days after vaccination [67].…”

“…BEI is used for the inactivation of many viruses, such as FMDV [70], RRV [75], sheep pox [76], HIV [77], Nipah virus [78], HNV [67] and PRRSV (Table 6) [79].…”

“…This procedure for virus inactivation has been tested to develop a KV vaccine against viruses such as rabbit hemorrhagic disease virus (RHDV) [92], murine leukemia virus strain Cas-Br-M [93] and PRRSV [79] and are summarized in Table 8.…”

“…Vaccination with UV-Cas protected mice against disease and reduced virus replication [93]. In addition, vaccination of pigs with UV-inactivated PRRSV induced virus-specific and virus-neutralizing antibody responses, which were able to reduce viremia after challenge [79]. However, there are also UV-inactivated vaccines that do not give protection against virus infection.…”

Different immunological features of two genetically distinct type 2 porcine reproductive and respiratory syndrome (PRRS) viruses

“…Thus, it stimulates delayed and weak protective immunity [i.e., serum virus neutralizing (SVN) antibody and interferon (IFN)-γ secreting T cells] which seldom appears until 3 to 4 weeks after infection (Meier et al, 2003;Faaberg et al, 2006;Vanhee et al, 2009). Passively acquired SVN antibody alone was proven to prevent viremia and reproductive failure in pigs challenged with virulent PRRSV strains (Osorio et al, 2002), suggesting the critical role of SVN antibody in the control of virus infection.…”