Intranasal Nanovaccine Confers Homo‐ and Hetero‐Subtypic Influenza Protection

Abstract

Cross-protective and non-invasively administered vaccines are attractive and highly desired for the control of influenza. Self-assembling nanotechnology provides an opportunity for the development of vaccines with superior performance. In this study, an intranasal nanovaccine is developed targeting the conserved ectodomain of influenza matrix protein 2(M2e). 3-sequential repeats of M2e (3M2e) is presented on the self-assembling recombinant human heavy chain ferritin (rHF) cage to form the 3M2e-rHF nanoparticle. Intranasal vaccination with 3M2e-rHF nanoparticles in the absence of an adjuvant induces robust immune responses, including high titers of sera M2e-specific IgG antibodies, T-cell immune responses, and mucosal secretory-IgA antibodies in mice. The 3M2e-rHF nanoparticles also confer complete protection against a lethal infection of homo-subtypic H1N1 and hetero-subtypic H9N2 virus. An analysis of the mechanism of protection underlying the intranasal immunization with the 3M2e-rHF nanoparticle indicates that M2e-specific mucosal secretory-IgA and T-cell immune responses may play critical roles in the prevention of infection. The results suggest that the 3M2e-rHF nanoparticle is a promising, needle-free, intranasally administered, cross-protective influenza vaccine. The use of self-assembling nanovaccines could be an ideal strategy for developing vaccines with characteristics such as high immunogenicity, cross-protection, and convenient administration, as well as being economical and suitable for large-scale production.

Heterosubtypic influenza protection elicited by double-layered polypeptide nanoparticles in mice

“…Because our peptides include known specific epitopes only (MHC-I-restricted epitope NP 147 and MHC-II-restricted epitope NP 55 ), the resulting peptides can induce CD8 + CTL and CD4 + Th-1 responses. However, as proven by many studies, minimal antigenic epitopes are often poorly immunogenic (50).…”

Nanoparticle-Based Vaccines Against Respiratory Viruses

“…These N-nanorings are interesting for intranasal delivery of antigen due to their similarities with respiratory viruses in term of size and structure (sub-nucleocapsid-like superstructures). Other examples of SAPNs as potential nanovaccines against respiratory viruses include the capsid protein of the papaya mosaic virus (PapMV), the purified coronavirus spike protein and ferritin, which are selfassembling proteins that form rod-shaped and nearly spherical nanostructures, respectively (96,(130)(131)(132)(133)(134)(135)(136)(137)(138)(139)(140). Recently, assemblies composed of four tandem copies of M2e and headless HA proteins were prepared and stabilized by sulfosuccinimidyl propionate crosslinking, showing the possibility of generating protein nanoparticles almost entirely composed of the antigens of interest (141).…”

Designing self-assembled peptide nanovaccine against Streptococcus pneumoniae: An in silico strategy

“…In this regard, the sequences 271-290, and 331-350 were selected as universal T-helper epitopes in our study. The efficacy of nanovaccines were confirmed in different investigations, including influenza nanovaccine [57], chitosan nanoparticle against H1N1 influenza virus [58], and chaitosan-formulated polyepitope vaccine against pulmonary mycobacterial [59]. Another important approach for increasing the immunogenicity of peptide vaccine is the use of self-assembled peptide structures, including alpha helical or beta sheet motifs, which can obtain from natural or de novo structures.…”