Vaccination with Deglycosylated Modified Hemagglutinin Broadly Protects against Influenza Virus Infection in Mice and Ferrets

Limin Zhang; Junyu Chen; Chenguang Shen; Guosong Wang; Zhen Lu; Dian Zeng; Ying Gao; Huiqing Chen; Ningshao Xia; Yixin Chen

doi:10.3390/vaccines10081304

Vaccination with Deglycosylated Modified Hemagglutinin Broadly Protects against Influenza Virus Infection in Mice and Ferrets

Vaccines (Basel). 2022 Aug 11;10(8):1304. doi: 10.3390/vaccines10081304.

Authors

Limin Zhang¹, Junyu Chen², Chenguang Shen³, Guosong Wang², Zhen Lu², Dian Zeng¹, Ying Gao¹, Huiqing Chen¹, Ningshao Xia^{1

2}, Yixin Chen^{1

2}

Affiliations

¹ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, China.
² State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361102, China.
³ Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.

Abstract

Recent efforts have been directed toward the development of universal influenza vaccines inducing broadly neutralizing antibodies to conserved antigenic supersites of Hemagglutinin (HA). Although several studies raise the importance of glycosylation in HA antigen design, whether this theory can be widely confirmed remains unclear; which influenza HA with an altered glycosylation profile could impact the amplitude and focus of the host immune response. Here, we evaluated the characteristics and efficacy of deglycosylated modified HA proteins, including monoglycosylated HA (HA_mg), unglycosylated HA (HA_ug), and fully glycosylated HA (HA_fg), without treatment with H3N2 Wisconsin/67/2005. Our results showed that HA_ug could induce a cross-strain protective immune response in mice against both H3N2 and H7N9 subtypes with better antibody-dependent cellular cytotoxicity (ADCC) than the HA_mg- and HA_fg-immunized groups, which suggested that highly conserved epitopes that were masked by surface glycosylation may be exposed and thus promote the induction of broad antibodies that recognize the hidden epitopes. This strategy may also supplement the direction of deglycosylated modified HA for universal influenza vaccines.

Keywords: Hemagglutinin; deglycosylation modification; glycosylation; universal influenza vaccine.

Abstract

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