Efficient, adjuvant-free mucosal vaccination via IgA feedback loop

Technology Description

The IgA feedback loop is a natural regulatory mechanism of the mucosal immune system, whereby a portion of sIgAs patrolling the lumen is continually re-internalized by retro-transcytosis through the epithelium to the submucosal lymphatic tissue. If these sIgAs are loaded with an antigen, they are recognized as an immunostimulatory signal, leading to the production of further sIgAs and IgGs against the antigen. Previous mucosal vaccination methods that exploited retro-transcytosis have relied on externally produced sIgAs, which are effective on a small scale but cost-prohibitive on a larger scale. The present invention leverages the vast pool of naturally occurring sIgAs present in the mucosa by utilizing a vaccine conjugate consisting of an IgA-binder and the antigen of choice. The IgA-binder can be either an antigen against which most (if not all) individuals have sIgAs (e.g., SARS-CoV2 spike protein), or a universal IgA-binder that recognizes the IgAs’ conserved Fc-portion. The former approach offers high affinity and specificity, while the latter approach may have weaker and less specific binding but utilizes the entire pool of sIgAs present.

Upon binding of the vaccine conjugate to the sIgAs, a portion of the newly formed sIgA::vaccine complexes is transported to the mucosal immune cells, where it triggers a robust immune response against the antigen of interest. In vivo proof of concept has been demonstrated in mice vaccinated against the SARS-CoV2 spike protein (alpha vs. omicron). In both cases, the highest IgA and IgG titers were found in saliva, BALF, and serum (refer to Fig.). Notably, the IgA and IgG titers achieved with the present invention were consistently higher than those achieved with a standard protocol that employs an adjuvant.