A synthetic delivery vector for mucosal vaccination.

Area of Science:

• Vaccinology
• Immunology
• Protein Chemistry

Background:

• mRNA vaccines showed success against COVID-19 but have limitations.
• Current vaccines show modest CD8+ T cell responses and lack mucosal immunity.
• Mucosal immunity is crucial for preventing viral spread in the general population.

Purpose of the Study:

• To develop a novel dendritic cell-targeting mucosal vaccination vector.
• To create a synthetic delivery tool for enhanced vaccine efficacy.
• To generate STxB variants for antigen coupling and mucosal immunization.

Main Methods:

• Efficient chemical synthesis and in vitro folding of homopentameric STxB protein.
• Generation of STxB variants with bioorthogonal handles for antigen conjugation.
• Intranasal administration of STxB-antigen conjugates in a mouse model.

Main Results:

• Synthetic STxB exhibited comparable biophysical and intracellular trafficking to recombinant STxB.
• Chemically coupled STxB variants successfully delivered SARS-CoV-2 and HPV antigens.
• Intranasal vaccination induced robust mucosal immunity, including resident memory CD8+ T cells and IgA antibodies.

Conclusions:

• A novel synthetic antigen delivery tool, STxB, was developed for mucosal vaccination.
• This approach overcomes limitations of mRNA vaccines by inducing strong mucosal immunity.
• The synthetic STxB vector holds significant potential for addressing urgent medical needs in infectious disease prevention.