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Highly conserved hemagglutinin peptides of H1N1 influenza virus elicit immune response.

ABSTRACT: In the current study, two highly conserved (>?90%) H1N1 hemagglutinin peptides STDTVDTVLEKNVTVTHSVNL (H1) and KVNSVIEKMNTQFTAVGKEF (H2) containing multiple T-cell epitopes have been assessed for their immunogenic potential in vitro, subjecting peripheral blood mononuclear cells from healthy volunteers to repetitive stimulation of chemically synthesised H1 and H2 peptides, and measuring their interferon (IFN)-? level (ELISA) and proliferation (MTT assay). Further, these peptides were analysed for their binding affinity with 18 different human leukocyte antigen (HLA) class I and II by means of molecular docking. All seven samples tested for H1- and H2-induced IFN-? secretion were found to have enhanced IFN-? production. Six (H1) and five (H2) samples have shown proliferative response compared to unstimulated cells. Peptide-induced IFN-? secretion and proliferation in healthy samples represent the immunogenic potential of these peptides. Further, molecular docking results reveal that the peptides have comparable binding energy to that of native bound peptide for both HLA classes which indicates that these peptides have the capability to be presented by different HLA molecules required for T-cell response. Hence, these conserved immunogenic hemagglutinin peptides are potential candidates for influenza vaccine development.

SUBMITTER: Lohia N

PROVIDER: S-EPMC6242801 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Project description:Despite the availability of seasonal vaccines and antiviral medications, influenza virus continues to be a major health concern and pandemic threat due to the continually changing antigenic regions of the major surface glycoprotein, hemagglutinin (HA). One emerging strategy for the development of more efficacious seasonal and universal influenza vaccines is structure-guided design of nanoparticles that display conserved regions of HA, such as the stem. Using the H1 HA subtype to establish proof of concept, we found that tandem copies of an alpha-helical fragment from the conserved stem region (helix-A) can be displayed on the protruding spikes structures of a capsid scaffold. The stem region of HA on these designed chimeric nanoparticles is immunogenic and the nanoparticles are biochemically robust in that heat exposure did not destroy the particles and immunogenicity was retained. Furthermore, mice vaccinated with H1-nanoparticles were protected from lethal challenge with H1N1 influenza virus. By using a nanoparticle library approach with this helix-A nanoparticle design, we show that this vaccine nanoparticle construct design could be applicable to different influenza HA subtypes. Importantly, antibodies elicited by H1, H5, and H7 nanoparticles demonstrated homosubtypic and heterosubtypic cross-reactivity binding to different HA subtypes. Also, helix-A nanoparticle immunizations were used to isolate mouse monoclonal antibodies that demonstrated heterosubtypic cross-reactivity and provided protection to mice from viral challenge via passive-transfer. This tandem helix-A nanoparticle construct represents a novel design to display several hundred copies of non-trimeric conserved HA stem epitopes on vaccine nanoparticles. This design concept provides a new approach to universal influenza vaccine development strategies and opens opportunities for the development of nanoparticles with broad coverage over many antigenically diverse influenza HA subtypes.

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Highly conserved hemagglutinin peptides of H1N1 influenza virus elicit immune response.

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