Comparison of chicken immune responses after inoculation with H5 avian influenza virus-like particles produced by insect cells or pupae

Abstract

Introduction Novel clade 2.3.4.4 H5 highly pathogenic avian influenza virus (HPAIV) outbreaks have occurred since early 2015 in Taiwan and impacted the island economically, like they have many countries. This research investigates the immunogenicity of two HPAIV-like particles to assess their promise as vaccine candidates. Material and Methods The haemagglutinin (HA) gene derived from clade 2.3.4.4 H5 HPAIV and matrix protein 1 (M1) gene were cloned into the pFastBac Dual baculovirus vector. The resulting recombinant viruses were expressed in Spodoptera frugiperda moth (Sf)21 cells and silkworm pupae to generate Sf21 virus-like particles (VLP) and silkworm pupa VLP. Two-week-old specific pathogen–free chickens were immunised and their humoral and cellular immune responses were analysed. Results The silkworm pupa VLP had higher haemagglutination competence. Both VLP types elicited haemagglutination inhibition antibodies, anti-HA antibodies, splenic interferon gamma (IFN-γ) and interleukin 4 (IL-4) mRNA expression, and CD4+/CD8+ ratio elevation. However, chickens receiving silkworm pupa VLP exhibited a significantly higher anti-HA antibody titre in ELISA after vaccination. Although Sf21 VLP recipients expressed more IFN-γ and IL-4, the increase in IFN-γ did not significantly raise the CD4+/CD8+ ratio and the increase in IL-4 did not promote anti-HA antibodies. Conclusion Both VLP systems possess desirable immunogenicity in vivo. However, in respect of immunogenic efficacy and the production cost, pupa VLP may be the superior vaccine candidate against clade 2.3.4.4 H5 HPAIV infection.

Single Dose of Bivalent H5 and H7 Influenza Virus-Like Particle Protects Chickens Against Highly Pathogenic H5N1 and H7N9 Avian Influenza Viruses

“…Furthermore, compared with the commercial whole-virus inactivated vaccines, an additional benefit of the VLP vaccines is the capacity of differentiating infected from vaccinated animals (DIVA) since VLP vaccines do not induce antibodies to the viral internal proteins, such as the NP protein (26,30). Lastly, single vaccination of chickens with the bivalent VLP elicited immunogenicity and conferred clinical protection comparable to that elicited by booster with other VLP vaccination (32,36,39,45). However, for ultimately being proposed as a critical alternative to the traditional ovoculture vaccines in poultry, some challenges still need to be addressed for the VLP vaccine, mainly including optimization of the manufacturing processes to achieve higher antigen yields, minimization of the downstream processing cost of vaccine manufacturing as well as enhancements of broad protection against multiple variants and subtypes of influenza virus.…”

“…Furthermore, VLP vaccines can provide excellent protection against homologous, heterologous, and heterosubtypic virus infections (9,(17)(18)(19), attributing to its strong ability to stimulate a comprehensive immune response, including humoral, mucosal, and cellular immunities (20)(21)(22)(23)(24). Numerous studies have been conducted to generate poultry VLP vaccines and the majority of these studies centered on production of H5 VLP in various expression systems, including baculovirus (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37), silkworm pupae (38,39), and mammalian 293T cells (40), for chicken or duck use. In addition, VLP candidates against other subtypes, such as the H6 and H7 subtypes, were also generated for chicken vaccination, including plant expression system for H6 VLP (41,42), chicken H7 VLP generated from baculovirus (43), and silkworm pupae (44), as well as Escherichia coli (45).…”

Supplementation of H7N9 Virus-Like Particle Vaccine With Recombinant Epitope Antigen Confers Full Protection Against Antigenically Divergent H7N9 Virus in Chickens

“…Avian influenza VLPs retain the structural and antigenic properties of native viruses but lack the genetic material, which is a better selection as vaccine antigen for the development of influenza vaccine. Influenza VLPs have been generated in various production platforms, including plant cells ( 39 , 40 ), hepatitis B virus core (HBc) ( 41 , 42 ), insect cells ( 11 , 43 ), and mammalian cells ( 44 ). Commercially, the method for producing influenza VLPs using a baculovirus expression vector system (BEVS) is safe and low cost.…”

“…Thus, the preparation approach of an influenza vaccine based on VLPs is preferable (9,10). The insect cellbaculovirus expression vector system (IC-BEVS) is widely used for the development of influenza VLP subunit vaccines owing to its unique advantages, including excellent safety, short production times, and straightforward scale-up (11)(12)(13). The production of VLPs based on insect cell suspension cultured in a bioreactor system is low cost and high yield (12,14).…”

The relationship among avian influenza, gut microbiota and chicken immunity: an updated overview

“…Successful invasion of the mucous layer, AIV primarily targets the respiratory and intestinal epithelia, resulting in the rapid killing of infected cells ( Kaufmann et al, 2001 ; Huang et al, 2021 ). The viral RNA is identified by different pattern recognition receptors ( PRR ) of the innate immune system, leading to the production of proinflammatory cytokines such as type-I interferons ( IFN ), chemokines, and eicosanoids ( Iwasaki and Pillai, 2014 ).…”