Single dose of multi-clade virus-like particle vaccine protects chickens against clade 2.3.2.1 and clade 2.3.4.4 highly pathogenic avian influenza viruses

Abstract

Virus-like particles (VLPs) are recognized as an alternative vaccine platform that provide effective protection against various highly pathogenic avian influenza viruses (HPAIVs). Here, we developed multi-clade VLPs expressing two HAs (a chimera of clade 2.3.2.1c and clade 2.3.4.4c HA) within a single vector. We then compared its protective efficacy with that of a monovalent VLP and evaluated its potency against each homologous strain. Chickens vaccinated with the multi-clade VLP shed less virus and were better protected against challenge than birds receiving monovalent vaccines. Single vaccination with a multi-clade VLP resulted in 100% survival, with no clinical symptoms and high levels of pre-challenge protective immunity (7.6–8.5 log2). Moreover, the multi-clade VLP showed high productivity (128–256 HAU) both in the laboratory and on a large scale, making it cheaper than whole inactivated vaccines produced in eggs. However, the PD50 (protective dose 50%) of the multi-clade VLP against clades 2.3.2.1c and 2.3.4.4c was < 50 PD50 (28 and 42 PD50, respectively), and effective antibody response was maintained for 2–3 months. This multi-clade VLP protects against both clades of HPAI viruses and can be produced in high amounts at low cost. Thus, the vaccine has potential as a pandemic preparedness vaccine.

Investigation of Avian Influenza H5N6 Virus-like Particles as a Broad-Spectrum Vaccine Candidate against H5Nx Viruses

“…In addition to generating broad-spectrum VLPs with single HA as vaccine candidate, scientists had also proposed some other strategies for VLP-based vaccine development. Kang et al exploited multi-clade VLPs carrying two HAs derived from two clades, clade 2.3.2.1c and clade 2.3.4.4c, within a single vector, and found that multi-clade VLPs not only show high productivity but also induced effective antibodies [ 14 ]. In contrast to variable surface antigens of HA and NA, the ion channel protein, Matrix protein 2 ectodomain (M2e), represents an alternative antigen target for AVI vaccine, since M2e protein has a relatively conserved sequence and plays a critical role in virus assembly and budding during replication.…”

“…Since the immune response to CFA, IFA and commercial oil-based adjuvants such as Montanide ISA 70VG, 71VG, 760VG, GEL01, etc., were in a large variation [ 28 ], the use of CFA and IFA might not be able to exactly mimic the clinical situations. We used CFA and IFA for the purpose of evaluating immune response between H5N6-VLPs and H5N6 protein, while ISA 71 VG and Montanide ISA VG70 oil adjuvant might be a better choice to compare the results with others [ 14 , 30 ].…”

“…For example, Wu et al fused a conserved M2e protein at the N-terminus of HA, or at the N-terminus of NA in the H5N1 VLP, to protect against heterosubtypic H1N1 and H5N1 [ 13 ]. Kang et al have expressed two HAs derived from a different clade of AIVs to enhance robust immune response [ 14 ]; however, expression of multiple genes in one vector may also contribute to assembly instability due to the tandem repetition of similar sequences [ 15 ]. In this study, we supposed that the conformation of VLP presenting the HA and NA may be similar to the native virions that induced antibodies and will be able to target the HA, which can effectively inhibit viral replication.…”

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

“…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).…”

Neuraminidase in Virus-like Particles Contributes to the Protection against High Dose of Avian Influenza Virus Challenge Infection

“…Virus-like particles (VLPs) are highly immunogenic vaccine platforms and efficacies forms of VLP-based vaccines are actively being investigated against a wide array of infectious diseases, including avian influenza. To date, several studies demonstrated that avian influenza HA-expressing VLP vaccines can induce protection [6][7][8][9]. Neuraminidase (NA) is another glycoprotein expressed on the surface of influenza viruses and a strong correlation between the NA antigen and protection can be drawn [10].…”