Microneedle coronavirus vaccine triggers immune response in mice

At a Glance When delivered to mice using microneedles, an experimental vaccine for COVID-19 caused antibody production against the disease within two weeks.

Long-term results from the animal experiments are pending, but the researchers have begun the process of obtaining permission for human clinical trials.

UPMC

On March 11, 2020, the World Health Organization designated COVID-19, the disease caused by the novel coronavirus SARS-CoV-2, an international pandemic. By April 6, the disease had infected over a million people around the world. More than 70,000 have died. Treatments and vaccines for COVID-19 are urgently needed to reverse the tide of this pandemic.

After the identification of SARS-CoV-2, the genome sequence of the new coronavirus was rapidly released to the public by scientists in China. Several weeks later, NIH-funded scientists produced a detailed picture of the part of the virus, called the spike protein, that allows it to infect human cells. This spike protein is currently the target of several vaccine development efforts.

Researchers led by Drs. Louis Falo, Jr. and Andrea Gambotto from the University of Pittsburgh have been working to develop vaccines for other coronaviruses, including the one that causes Middle East Respiratory System (MERS). They adapted the system they had been developing to produce a candidate MERS vaccine to rapidly produce an experimental vaccine using the SARS-CoV-2 spike protein.

The study was funded by NIH’s National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and National Cancer Institute (NCI). It appeared online on April 1, 2020, in EBioMedicine, a Lancet journal.

The team developed a method for delivering their MERS vaccine into mice using a microneedle patch. Such patches resemble a piece of Velcro, with hundreds of tiny microneedles made of sugar. The needles prick just into the skin and quickly dissolve, releasing the vaccine. Since the immune system is highly active in the skin, delivering vaccines this way may produce a more rapid and robust immune response than standard injections under the skin.

When delivered by microneedle patch to mice, three different experimental MERS vaccines induced the production of antibodies against the virus. These responses were stronger than the responses generated by regular injection of one of the vaccines along with a powerful immune stimulant (an adjuvant). Antibody levels continued to increase over time in mice vaccinated by microneedle patch—up to 55 weeks, when the experiments ended.

Using knowledge gained from development of the MERS vaccine, the team made a similar microneedle vaccine targeting the spike protein of SARS-CoV-2. The vaccine prompted robust antibody production in the mice within two weeks.

The vaccinated animals haven’t been tracked for enough time to see if the long-term immune response is equivalent to that observed with the MERS vaccines. The mice have also not yet been challenged with SARS-CoV-2 infection. However, the findings are promising in light of results from the similar MERS vaccine.

The components of the experimental vaccine could be made quickly and at large-scale, the researchers say. The final product also doesn’t require refrigeration, so it could be produced and placed in storage until needed. The team has now begun the process of obtaining approval from the U.S. Food and Drug Administration to launch a phase 1 trial within the next several months.

Much work still needs to be done to explore the safety and efficacy of this candidate vaccine. “Testing in patients would typically require at least a year and probably longer,” Falo says. “This particular situation is different from anything we’ve ever seen, so we don’t know how long the clinical development process will take.”