Gold Nanoparticle–M2E Conjugate Coformulated with Cpg Induces Protective Immunity Against Influenza A Virus

Abstract

Aim: This study aimed to develop a novel influenza A vaccine by conjugating the highly conserved extracellular region of the matrix 2 protein (M2e) of influenza A virus to gold nanoparticles (AuNPs) and to test the vaccine in a mouse influenza challenge model. Materials & methods: Citrate-reduced AuNPs (diameter: 12 nm) were synthesized, and characterized by transmission electron microscopy and dynamic light scattering. M2e was conjugated to AuNPs through thiol–gold interactions to form M2e–AuNP conjugates. Particle stability was confirmed by UV–visible spectra, and M2e conjugation was further characterized by x-ray photoelectron spectroscopy. Mice were immunized with M2e–AuNPs with or without CpG (cytosine-guanine rich oligonucleotide) as an adjuvant with appropriate control groups. Sera was collected and M2e-specific immunoglobulin (IgG) was measured, and immunized mice were challenged with PR8-H1N1 influenza virus. Results: M2e-capped AuNPs could be lyophilized and stably resuspended in water. Intranasal vaccination of mice with M2e–AuNP conjugates induced M2e-specific IgG serum antibodies, which significantly increased upon addition of soluble CpG as adjuvant. Upon challenge with lethal PR8, mice vaccinated with M2e-AuNP conjugates were only partially protected, while mice that received soluble CpG as adjuvant in addition to M2e–AuNP were fully protected. Conclusion: Overall, this study demonstrates the potential of using the M2e–AuNP conjugates with CpG as an adjuvant as a platform for developing an influenza A vaccine.

Oral delivery of nanoparticle-based vaccines

“…Gold NPs conjugated with different antigenic peptides and polymers (poly acrylic acids and chitosan) are stable in acidic solutions [116,118]. It has been shown that gold NPs conjugated to antigenic peptide, matrix 2 protein, induced an antigen-specific IgG response when administered thorough nasal mucosal routes [122]. They were also efficient for boosting the immune response induced by intramuscularly vaccination of DNA making it suitable as a novel immunoadjuvant [123].…”

Biomimetic gold nanocomplexes for gene knockdown: Will gold deliver dividends for small interfering RNA nanomedicines?

“…For example, Helmut et al conjugated AuNPs to trypsin-NH 2 via immobilization through 1-ethyl-3-(3-dimethylaminopropylcarbodiimide/N-hydroxysuccinimide (EDC/NHS) bioconjugation onto functional carboxylic AuNPs (AuNP-S-Spacer-COO -) to generate AuNPs-trypsin with an amide linkage [82]. In addition, Tao et al synthesized M2e-conjugated AuNPs via thiol-gold interactions, which could be lyophilized and stably re-suspended in water [83]. M2e is the highly conserved extracellular region of the matrix 2 protein of the influenza A virus.…”

Use of a synthetic foot-and-mouth disease virus peptide conjugated to gold nanoparticles for enhancing immunological response

“…Although not containing adjuvants, the proposed experimental vaccine offered better protection than did its commercial counterparts. Subsequently, AuNPs have been used to generate antibodies and design experimental vaccines (both peptide and carbohydrate) against influenza A virus [26,27], transmissible gastroenteritis virus [28], West Nile virus [29], the respiratory syncytial virus [30], as well as against tuberculosis [31,32] and other bacterial infections [33][34][35][36][37]. In addition, AuNPs are being used in the development of experimental vaccines against tumors [38,39].…”