Immunization with deglycosylated H7N9 VLP enhances cross-strain protective antibody responses against avian influenza H7N9 variants in mice

Introduction The rapidly evolving avian influenza H7N9 virus remains a threaten to public health globally. There is an urgent need to develop broad-spectrum vaccines capable of eliciting functional cross-strain protective immunity against emerging viral variants. Methods N-linked glycosylation can shield critical residues from immune recognition. Here, a prototype virus-like particle (VLP) was constructed based on the antigenic sequences derived from A/Taiwan/1/2013 H7N9 virus. Glycosidase enzymes were utilized to trim the glycan molecules for generating monoglycosylated VLP (VLPmg) and nonglycosylated VLP (VLPng) derivates. The structural integrity, antigenicity, and immunogenicity of these VLPs were systematically evaluated. Results Both VLPmg and VLPng maintained hemagglutination activity and antigenicity like the fully glycosylated prototype VLP (VLPfg). Immunization with deglycosylated VLPs induced robust virus-specific antibodies and a balanced Th1/Th2 immune profile in mice, whereas the titers were comparable to that of VLPfg. Among them, VLPng induced higher hemagglutination inhibition and neutralizing antibody titers against different H7N9 virus strains, indicating improved cross-strain reactive antibody responses. Conclusion This study demonstrated the enzymatic deglycosylation of influenza H7N9 VLP improves the induction of broadly protective antibody responses in mice. The nonglycosylated H7N9 VLP represents a potential vaccine candidate to against the threat of antigenically divergent H7N9 virus variants.