A team led by Drs. Louis Falo and Andrea Gambotto at the University of Pittsburgh have reported a COVID-19 vaccine that is delivered on small patches with 100 soft plastic needles. The vaccine was generated using a fragment of the spike protein that coronaviruses use to bind receptors to get into cells. After the mice received the vaccine, serum from them was diluted 100-fold, and incubated on a plate coated in the COVID-19 spike protein fragment. The serum successfully detected the protein when the mice had been immunized for ≥ 2 weeks (it detected the protein on an ELISA plate coated with it). However, the following questions remain unclear:
- Are the antibodies generated using this vaccine actually capable of neutralizing the virus and preventing infection?
- Will a similar vaccine produce a useful antibody response in humans?
The COVID-19 work in this paper was tacked on at the end. The primary focus of this paper was on MERS vaccines, however. You may recall that MERS is another very dangerous coronavirus (34.4% case fatality rate). It hasn’t spread particularly far outside the Middle East, save for a 2015 outbreak in South Korea, and only 2,513 confirmed cases have been reported. However, the MERS virus still remains endemic in Saudi Arabia. There are long-term MERS experiments reported in this work (including a 55-week experiment showing the durability of the response to the vaccine), suggesting that this research has been underway for quite some time. It is likely that the work was begun when back when the MERS threat loomed large, prompting significant interest and funding in the work. Unfortunately, we tend to lose interest and stop funding important work when it’s not plastered all over the headlines we read, so the MERS work likely lost steam until the COVID-19 “money experiment” was tacked on to the end of this manuscript. In other news, we are still waiting for a Zika virus vaccine/treatment (though it will take several years even with lots of interest/money thrown at the problem)…
The researchers should be commended for their great speed in delivering these promising early results. The sequence of the COVID-19 spike protein has not been known for very long, and they were able to clone the gene into a plasmid (with and without an “RS09” peptide adjuvant tacked on), express and purify the protein from mammalian cells, characterize the protein, fabricate the vaccine, test it in mice, and run the ELISA. This was all done with a “skeleton crew” remaining at the University of Pittsburgh, which is almost entirely shut down save for a few research projects deemed to be essential.
The vaccine is certainly on an interesting platform. Dr. Falo’s start-up company, SkinJect, has been developing these patches for quite some time. The patch-based vaccine supposedly doesn’t hurt that much compared to metal needles. It doesn’t need to be refrigerated, is easy to manufacture quickly at a large scale (a small academic laboratory can put together a few hundred in short order), works after you sterilize it with gamma irradiation, and is easy to apply anywhere (you can immunize yourself). Based on the MERS data, the SkinJect platform raises a better antibody response than traditional injected vaccines, likely the intradermal delivery with a bit of inflammation provoked by the needles primes the immune system to respond effectively. It remains unclear how the COVID-19 patch-based would compare to a traditional injectable.
Ths was a impressive proof-of-concept rolled out in record time, but no one knows if the vaccine is actually effective, or if it will translate to humans. Still, these investigators are to be commended for their continued hard work and ingenuity at this difficult time.
Link to the paper (free of charge):
Kim, E. et al. “Microneedle array delivered recombinant coronavirus vaccines:
Immunogenicity and rapid translational development.” EBioMedicine (2020), https://doi.org/10.1016/j.ebiom.2020.102743.
Med School Beast 