The US government is funding four groups developing technologies to administer COVID-19 vaccines via skin patches or pills. The Biomedical Advanced Research and Development Authority (BARDA) has provided about $2.5 million in total to Esperovax, the University of Connecticut, Vaxess Technologies, and Verndari.

The sum is small compared with the billions of dollars that BARDA has committed to vaccine companies such as AstraZeneca, Moderna, and Pfizer, which are testing their COVID-19 vaccines in large clinical studies. Yet the investment suggests BARDA is interested in vaccines that do not rely on needles, syringes, and medical glass.

This summer, drug company executives warned that potential shortages of these materials could delay the distribution of vaccines. Once the vaccines are available, already-stretched medical professionals may find millions of people at their doors waiting for shots. Patch- and pill-based vaccines, in contrast, could be shipped directly to people via mail and self-administered.

The University of Connecticut, Vaxess, and Verndari are all using microneedles to deliver viral proteins into the skin, where they should induce an immune response. UConn received $433,000, Vaxess got $749,000, and Verndari got $698,000.

The patches will contain the SARS-CoV-2 spike protein—the basis of nearly all COVID-19 vaccines. The patches are intended to be shelf-stable and release the spike protein into the body slowly over a few weeks. In theory, that could eliminate the need for repeated vaccinations. The most advanced COVID-19 vaccines require two shots given about a month apart.

Esperovax, which received $607,000 from BARDA, is taking a different approach. Its experimental pill-based vaccine uses baker’s yeast engineered to secrete lipid particles that contain messenger RNA encoding the spike protein. These particles are intended to stimulate the immune cells of the gut.

None of these groups has ever made a commercial vaccine. Vaxess, the most advanced and well funded, previously tested its microneedle patch in a Phase I study of an influenza vaccine. Earlier this year, Vaxess said its first COVID-19 vaccine would not be ready for launch until October 2021 at best.