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A Cross-Reactive Monoclonal Antibody Against Neuraminidases of Both H9N2 and H3N2 Influenza Viruses Shows Protection in Mice Challenging Models.

ABSTRACT: Neuraminidases (NAs) of H9N2 avian influenza virus (AIV) and H3N2 human seasonal influenza virus (HSIV) share similar antigenic structures. However, there are few reports on epitopes shared by these two NAs. We previously reported a monoclonal antibody (mAb) 1G8 against the NA of H9N2 AIV with neuraminidase inhibition (NI) ability. In this study, 1G8 was shown to cross-react with and inhibit the NA of H3N2 HSIV. In a passive transfer experiment, 1G8 provided protection to mice challenged with rescued H1N2 viruses carrying H9N2 NA or H3N2 NA. Mutation at amino acid position 199 was also selected and proved to be crucial for H3N2 HSIV to escape from mAb 1G8. Moreover, we found that residue 199 contributed to inducing broad protective antibodies without the influence of the N-linked glycosylation at amino acid position 200 in NAs. Residues as residue 199, which are not shielded by glycosylation modification, would form ideal epitopes for developing universal vaccine and protective antibodies.

SUBMITTER: Wang F

PROVIDER: S-EPMC8503672 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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A Cross-Reactive Monoclonal Antibody Against Neuraminidases of Both H9N2 and H3N2 Influenza Viruses Shows Protection in Mice Challenging Models.

Wang Fei F Wan Zhimin Z Wu Jinsen J Wang Yajuan Y Fu Hui H Shao Hongxia H Qian Kun K Gao Wei W Ye Jianqiang J Qin Aijian A

Frontiers in microbiology 20210927

Neuraminidases (NAs) of H9N2 avian influenza virus (AIV) and H3N2 human seasonal influenza virus (HSIV) share similar antigenic structures. However, there are few reports on epitopes shared by these two NAs. We previously reported a monoclonal antibody (mAb) 1G8 against the NA of H9N2 AIV with neuraminidase inhibition (NI) ability. In this study, 1G8 was shown to cross-react with and inhibit the NA of H3N2 HSIV. In a passive transfer experiment, 1G8 provided protection to mice challenged with re ...[more]

PMID: 34646249

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Project description:Background/Objective: Highly pathogenic (HP) H5Nx and low-pathogenicity (LP) H9N2 avian influenza viruses (AIVs) pose global threats to the poultry industry and public health, highlighting the critical need for a dual-protective vaccine. Methods: In this study, we generated a model PR8-derived recombinant H5N2 vaccine strain with hemagglutinin (HA) and neuraminidase (NA) genes from clade 2.3.2.1c H5N1 and Y439-like H9N2 viruses, respectively. To enhance the immunogenicity of the recombinant H5N2 vaccine strain, N-glycans of the HA2 subunit, NA, and M2e were modified. Additionally, we replaced M2e with avian M2e to enhance the antigenic homogeneity of AIVs for better protection. We also replaced PR8 PB2 with 01310 PB2, which is the PB2 gene derived from an LP H9N2 avian influenza virus, to eliminate pathogenicity in mammals. The productivity of the model vaccine strain (rvH5N2-aM2e-vPB2) in embryonated chicken eggs (ECEs), its potential risk of mammalian infection, and the immunogenicity associated with different inactivation methods (formaldehyde (F/A) vs. binary ethyleneimine (BEI)) were evaluated. Results: The rvH5N2-aM2e-vPB2 strain demonstrated high productivity in ECEs and exhibited complete inhibition of replication in mammalian cells. Furthermore, compared with using F/A inactivation, inactivation using BEI significantly enhanced the immune response, particularly against NA. This enhancement resulted in increased virus neutralization titers, supporting its efficacy for dual protection against H5Nx and H9N2 avian influenza viruses. Furthermore, we demonstrated that M2e-specific immune responses, difficult to induce with inactivated vaccines, can be effectively elicited with live vaccines, suggesting a strategy to enhance M2e immunogenicity in whole influenza virus vaccines. Conclusions: Finally, the successful development of the model rH5N2 vaccine strain is described; this strain provides dual protection, has potential applicability in regions where avian influenza is endemic, and can be used to promote the development of versatile H5N2 recombinant vaccines for effective avian influenza control.

Dataset Information

A Cross-Reactive Monoclonal Antibody Against Neuraminidases of Both H9N2 and H3N2 Influenza Viruses Shows Protection in Mice Challenging Models.

Publications

A Cross-Reactive Monoclonal Antibody Against Neuraminidases of Both H9N2 and H3N2 Influenza Viruses Shows Protection in Mice Challenging Models.

Similar Datasets

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