Consensus M2e peptide conjugated to gold nanoparticles confers protection against H1N1, H3N2 and H5N1 influenza A viruses

Abstract

The extracellular domain of influenza A ion channel membrane matrix protein 2 (M2e) is considered to be a potential candidate to develop a universal influenza A vaccine. However poor immunogenicity of M2e presents a significant roadblock. We have developed a vaccine formulation comprising of the consensus M2e peptide conjugated to gold nanoparticles (AuNPs) with CpG as a soluble adjuvant (AuNP-M2e+sCpG). We demonstrate that intranasal delivery of AuNP-M2e+sCpG in mice induces lung B cell activation and robust serum anti-M2e immunoglobulin G (IgG) response, with stimulation of both IgG1 and IgG2a subtypes. Using Madin-Darby canine kidney (MDCK) cells infected with A/California/04/2009 (H1N1pdm) pandemic strain, or A/Victoria/3/75 (H3N2), or the highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1) as immunosorbants we further show that the antibodies generated are also capable of binding to the homotetrameric form of M2 expressed on infected cells. Lethal challenge of vaccinated mice with A/California/04/2009 (H1N1pdm) pandemic strain, A/Victoria/3/75 (H3N2), and the highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1) led to 100%, 92%, and 100% protection, respectively. Overall, this study helps to lay the foundation of a potential universal influenza A vaccine.

Prospects for the use of spherical gold nanoparticles in immunization

“…Markers protein markers (kDa) Protein P Protein N (50-62) Protein M (25-35) Protein 17K and Bcl-2 expression. Tao et al (2017) also revealed an increase in the concentration of cytokines including interferon gamma and interleukin 1 in response to immunization AuNP-M2e + sCpG. But he mainly considered the reaction of splenocytes to a given complex (their reaction, which was expressed in the production of cytokines, on the effect of AuNP) was studied.…”

Promising approaches for the treatment and prevention of viral respiratory illnesses

“…22 Currently, naturally occurring particles are favored because of safety concerns, 100 even though synthetic polymers, such as poly lactic-co-glycolic acid, are in use, 101 and gold nanoparticles have shown promising results. 102 Self-assembling protein nanoparticles, such as ferritin cages and vaults, have also shown promising preclinical data. 103,104 Layer-by-layer peptide-fabricated vaccine containing alternately charged poly-L-glutamic acid and poly-L-lysine layers with RSV peptides added have been efficacious in animals.…”

Antiviral activity of Isatidis Radix derived glucosinolate isomers and their breakdown products against influenza A in vitro/ovo and mechanism of action

“…Currently, therapeutic strategies to lower the mortality rates mainly rely on vaccines and chemical drugs. But usage of vaccines has been often challenged by frequent mutation of the antigen and narrow spectrum (Tao et al, 2017;Zarubaev et al, 2015). On the other side, viral resistance and adverse effects restrict the clinic application of currently available anti-influenza virus drugs including neuraminidase inhibitors, M2 channel blockers and RNA synthesis inhibitors (Hayden and De Jong, 2011;Samson et al, 2013;Correia et al, 2015).…”