Recombinant Pichinde Virus-Vectored Turkey Arthritis Reovirus Subunit Vaccine: Comparison
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Please note this is a comparison between Version 2 by Yvaine Wei and Version 1 by Sagar Goyal.

Turkey arthritis reovirus (TARV) causes lameness in turkeys, generally at 12–17 weeks of age. A recombinant live pichinde virus-vectored bivalent codon optimized subunit vaccine that expresses immunogenic Sigma C and Sigma B proteins of turkey arthritis reovirus was created. The vaccine virus could be transmitted horizontally immunizing the non-vaccinated pen mates. Comparison of virus gene copy numbers in intestine and histologic lesion scores in tendons of vaccinated and non-vaccinated birds showed a decrease in the replication of challenge viruses in the intestine and tendons of vaccinated birds. These results indicate the potential usefulness of this vaccine.

  • Turkey arthritis reovirus
  • recombinant vaccine
  • subunit vaccine
  • serum neutralizing antibodies

1. Introduction

A reovirus was isolated from the gastrocnemius tendons of turkeys affected with arthritis/tenosynovitis in the 1980s [1[1][2],2], but this condition was not observed for nearly 25 years until it was reported by Mor et al. [3]. Thereafter, several authors reported Turkey arthritis reovirus (TARV)-associated outbreaks of lameness in market age turkeys [4,5][4][5]. These outbreaks result in substantial economic losses to turkey farmers in the form of increased culling, increased condemnation rates, poor feed efficiency, and low rates of weight gain [4,6][4][6]. The disease has been experimentally reproduced to confirm the involvement of reovirus and the infection has consistently been associated with uni- or bilateral lameness due to swelling of the hocks, periarticular fibrosis, tenosynovitis, occasional erosion of the articular cartilage on distal tibiotarsus, and rupture of the gastrocnemius or digital flexor tendon [3,6,7,8][3][6][7][8].

The TARV is a member of genus Orthoreovirus in the family Reoviridae containing double-stranded segmented RNA genome in double-shelled capsid. The 10 segments of viral genome are classified as L class (L1–L3), M class (M1–M3), and S class (S1–S4) based on their electrophoretic mobility [9]. Reoviral genome has 12 open reading frames (ORFs), which encode eight structural and four nonstructural proteins [10]. Sigma C (SC) protein translated by the third ORF of S1 segment is an outer capsid cell attachment protein [11,12,13][11][12][13]. It is the most divergent among reovirus proteins and is the main immunogenic surface protein containing type- and broad-specific neutralizing epitopes [12]. Sigma B (SB) protein encoded by S3 segment is a major component of the viral outer capsid and contains a group-specific neutralizing epitope [14]. The SC protein alone or in combination with SB protein has been used in formulating subunit vaccines against avian reovirus infections [15,16,17,18][15][16][17][18].
Since 2011, breeder turkeys in the U.S. have been vaccinated with autogenous killed virus for TARV, but commercial market turkeys have not been vaccinated. Setbacks to a successful vaccination program for TARVs are the development of multiple variant TARV strains and the absence of a commercial vaccine. Recently, custom made autogenous vaccines with prevalent pathogenic TARV strains are being used by the turkey industry to vaccinate breeder turkeys. Breeders are being vaccinated to check the suspected vertical transmission and to provide maternally derived antibodies to the progeny in the initial days of their life. However, these autogenous vaccines are poorly characterized and show variable efficacy, especially against the variant strains [6]. Antigenic and genetic variants different from the vaccine strains have been reported from progeny and unvaccinated breeder flocks in the U.S. [3,5,8,19,20,21,22][3][5][8][19][20][21][22]. Outbreaks of TARV-associated lameness continue to be reported, and affected turkeys are generally sent to diagnostic labs.

2. Effectiveness of the rPICV-TARV Vaccine against Homologous and Heterologous Virus Challenge in the Vaccinated Poults

In chickens, vaccination for ARV is primarily completed with live attenuated vaccine administered to young chicks followed by inactivated vaccine before egg laying [28][23]. This regime was found to induce the highest level of immune response in birds [29][24]. The absence of a commercial vaccine against turkey arthritis reovirus poses the biggest hurdle in the vaccination program. The turkey industry has adopted a strategy of using polyvalent autogenous vaccines in breeders prepared from the prevalent strains in their flocks [22,30][22][25]. Custom made autogenous vaccines are not the long-term solution because there are inherent drawbacks with autogenous vaccines discussed in detail elsewhere [18,22][18][22]. Emergence of variant reoviruses, especially variation in their cell attachment and outer capsid proteins is another hurdle in vaccination, because these variations cause inadequate protection provided by commercial vaccines in the vaccinated flock and their progeny. OurThe approach was to develop a live subunit vaccine to overcome these issues because subunit vaccines have potential advantages over the conventional and autogenous vaccines. The live virus-vectored turkey arthritis reovirus vaccine provides an alternative to the use of autogenous vaccines which have the potential to promote the emergence of variant strains. The present study was designed to test the transmissibility and efficacy of the rPICV-TARV vaccine against homologous and heterologous virus challengee were designed to be tested. The rPICV-TARV vaccine expressing SC and SB antigenic proteins has been shown to elicit a humoral immune response producing serum neutralizing antibodies in turkeys in ourthe previous study [23][26]. Similarly, hemagglutinin and nucleoprotein genes of avian influenza virus (AIV) carried by rPICV vector to stimulate humoral and cell-mediated immune responses providing protection against pathogenic AIV in mice [31][27]. Previous studies have reported various subunit vaccines expressing SC and SB proteins against chicken and duck reoviruses [15,16,17,18][15][16][17][18]. Subunit vaccines against infectious bursal disease and adenovirus infection have previously been reported to be efficacious [31,32,33,34][27][28][29][30]. Turkey poults experimentally infected with TARV produce moderate to high antibody titers to whole chicken reovirus (commercial ELISA). A similar commercial reovirus ELISA showed negative results with no antibody titers in vaccinated poults. This is likely because the ELISA used here uses whole virus rather than subunits as antigen; hence, the whole virus did not optimally present adequate epitopes to detect antibodies to the SC and SB proteins produced by the subunit vaccine. The ELISA would have been more sensitive for ourthe purpose if subunits were used as the determinant antigen rather than whole virus [38][31]. The ELISA using SC and/or SB proteins targets for group and type-specific neutralizing antibodies as the coated antigen were reported to be better in predicting the level of neutralization antibodies than ELISA using the whole virus and showed a good correlation between ELISA and SNT [39,40][32][33].  At 21 and 28 doa, the virus gene copy numbers in the intestine and tendon of vaccinated-challenged (V-SKM and V-ON) and sentinel-challenged (Sen-SKM and Sen-ON) groups were numerically lower than the corresponding virus challenge-only groups (SKM and ON, respectively) suggesting that the subunit vaccine can inhibit virus replication in the intestine. These findings are likely attributable to the higher SN titers produced in the vaccinated and sentinel groups. Humoral immune response is the primary mechanism of providing protection against ARVs as antibodies produced against SC and SB proteins of ARVs inhibit virus attachment and cause lysis of virus and virus infected cells [22,46,47][22][34][35]. Additionally, the vaccine has provided similar protection against the homologous (TARV SKM121) and heterologous (TARV O’Neil) virus challenge. The vaccine was almost equally effective against heterologous virus challenge probably due to additional group-specific neutralizing antibodies induced by the SB protein of the vaccine. Precisely, SC protein elicits reovirus specific neutralizing antibodies and has been reported to elicit a strong mucosal immunity [48,49,50][36][37][38].

3. Conclusions

The rPICV-TARV bivalent codon optimized vaccine has a potential to be used for vaccination against TARV infection. It can have promising economic benefits for the industry if breeder immunization is practiced preventing vertical transmission [52][39]. In birds, better immunity is achieved with a live vaccine before using inactivated vaccine in breeders [29][24]. The additional advantages of the recombinant vaccine is: (1) the characterized gene segments (SC and SB) of new variants can be easily cloned into the rPICV virus which will immunize the birds against the variant strains; (2) other genes of outer capsid proteins, e.g., M2 (MuB), can be cloned into the rPICV virus for enhancing the spectrum of ourthe vaccine; (3) only gene segments translating to outer capsid proteins of variant TARVs are being used in the vaccine and not the whole viruses, eliminating the possibility of generation of variant TARVs. Useful information that the vaccine could control and prevent the infection is provided, thereby it paves a foundation for a promising potent future vaccine. Lastly, the importance of strict biosecurity and best management practices for maximizing vaccine efficacy in the prevention and control of reovirus infection in turkeys should not be ignored.

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