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

Bioconjug Chem. 2023 Aug 16;34(8):1447-1458. doi: 10.1021/acs.bioconjchem.3c00223. Epub 2023 Jul 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral
  • Dextrans / chemistry
  • Epitopes
  • Humans
  • Influenza A virus*
  • Influenza Vaccines*
  • Influenza, Human* / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics

Substances

  • Dextrans
  • Influenza Vaccines
  • Epitopes
  • Viral Matrix Proteins
  • Antibodies, Viral