Humoral Response to the Acetalated Dextran M2e Vaccine is Enhanced by Antigen Surface Conjugation

Abstract

The influenza A virus causes substantial morbidity and mortality worldwide every year and poses a constant threat of an emergent pandemic. Seasonal influenza vaccination strategies fail to provide complete protection against infection due to antigenic drift and shift. A universal vaccine targeting a conserved influenza epitope could substantially improve current vaccination strategies. The ectodomain of the matrix 2 protein (M2e) of influenza is a highly conserved epitope between virus strains but is also poorly immunogenic. Administration of M2e and the immunostimulatory stimulator of interferon genes (STING) agonist 3′3′-cyclic guanosine−adenosine monophosphate (cGAMP) encapsulated in microparticles made of acetalated dextran (Ace-DEX) has previously been shown to be effective for increasing the immunogenicity of M2e, primarily through T-cell-mediated responses. Here, the immunogenicity of Ace-DEX MPs delivering M2e was further improved by conjugating the M2e peptide to the particle surface in an effort to affect B-cell responses more directly. Conjugated or encapsulated M2e co-administered with Ace-DEX MPs containing cGAMP were used to vaccinate mice, and it was shown that two or three vaccinations could fully protect against a lethal influenza challenge, while only the surface-conjugated antigen constructs could provide some protection against lethal challenge with only one vaccination. Additionally, the use of a reducible linker augmented the T-cell response to the antigen. These results show the utility of conjugating M2e to the surface of a particle carrier to increase its immunogenicity for use as the antigen in a universal influenza vaccine.

Clinical and Preclinical Methods of Heat-Stabilization of Human Vaccines

“…Additionally, some of these materials can also stabilize the vaccine elements outside the cold chain. Several types of formulations exist that encapsulate vaccine elements into a polymeric matrix or lipid particle (Figure ); they can also be covalently bound to the surface. , Vaccine elements are most commonly encapsulated into spherical particles that are (polymeric nano/microparticles [NPs]), nucleic acid complexing LNPs, or virosomes). Virosomes are liposomes containing virus elements (e.g., proteins, inactivated viruses) that have lipid-anchored antigens on the surface of the particles .…”