Protection against infectious bronchitis virus by spike ectodomain subunit vaccine

Abstract

The avian coronavirus infectious bronchitis virus (IBV) S1 subunit of the spike (S) glycoprotein mediates viral attachment to host cells and the S2 subunit is responsible for membrane fusion. Using IBV Arkansas-type (Ark) S protein histochemistry, we show that extension of S1 with the S2 ectodomain improves binding to chicken tissues. Although the S1 subunit is the major inducer of neutralizing antibodies, vaccination with S1 protein has been shown to confer inadequate protection against challenge. The demonstrated contribution of S2 ectodomain to binding to chicken tissues suggests that vaccination with the ectodomain might improve protection compared to vaccination with S1 alone. Therefore, we immunized chickens with recombinant trimeric soluble IBV Ark-type S1 or S-ectodomain protein produced from codon-optimized constructs in mammalian cells. Chickens were primed at 12days of age with water-in-oil emulsified S1 or S-ectodomain proteins, and then boosted 21days later. Challenge was performed with virulent Ark IBV 21days after boost. Chickens immunized with recombinant S-ectodomain protein showed statistically significantly (P<0.05) reduced viral loads 5days post-challenge in both tears and tracheas compared to chickens immunized with recombinant S1 protein. Consistent with viral loads, significantly reduced (P<0.05) tracheal mucosal thickness and tracheal lesion scores revealed that recombinant S-ectodomain protein provided improved protection of tracheal integrity compared to S1 protein. These results indicate that the S2 domain has an important role in inducing protective immunity. Thus, including the S2 domain with S1 might be promising for better viral vectored and/or subunit vaccine strategies.

Greater Protection against Virulent Infectious Bronchitis Virus Challenge Conferred by Recombinant Baculovirus Co-expressing S1 and N Proteins

“…The reason was that rHBM-S1-N expressed both the S1 and N proteins of IBV and stimulated both the humoral and cellular immune responses simultaneously, therefore the subunit vaccine rHBM-S1-N performed better in the activation of virus-specific immune responses. Although the S1 subunit is the major inducer of neutralizing antibodies, vaccination with S1 protein couldn't confer adequate protection against challenge [17]. A previous study even found that the antigenicity of N protein is better than that of the spike protein [37].…”

“…Hence, there is an urgent need to develop new, safe and effective vaccines to control the disease. Recombinant subunit vaccines have been shown to elicit strong humoral and cellular immune responses and be very safe [16][17][18]. Therefore subunit vaccines may serve as potential vaccine candidates in the future.…”

“…Among new vaccines, subunit vaccines have been showed to elicit strong humoral and cellular immune responses [16][17][18]. Subunit vaccines have significant advantages of efficient antigenic presentation, high stability, and flexibility in proteins or epitopes selection compared with live-attenuated and inactivated vaccines [16].…”

Peptides with 16R in S2 protein showed broad reactions with sera against different types of infectious bronchitis viruses

“…Among these proteins, S glycoprotein is the major protective antigen carrying neutralizing epitopes and can induce efficient immune responses against IBV Galli, 1993, 1995;Kant et al, 1992). Notably, S protein can be cleaved into the amino-terminal S1 and carboxy-terminal S2 domains by a furine-like protease from the host (Cavanagh, 2007;Eldemery et al, 2017;Kusters et al, 1989). S1 is responsible for IBV attachment to host cells, whereas S2 contributes to viral fusion activity of IBV (Wickramasinghe et al, 2014).…”

“…S2 protein expressed from recombinant virus confers broad protection against challenge (Toro et al, 2014). Therefore, S2 protein has important roles in inducing protective immunity (Eldemery et al, 2017). Moreover, (Kusters et al, 1989) in S2 have been identified as broad or neutralizing epitopes for IBV (Andoh et al, 2018;Ignjatovic and Sapats, 2005).…”