Vaccinating into skin instead of muscles could mean many more people can be immunized

May 2021 Covid-19 Willem van Altena

Interview with dr. Anna Roukens, Infectiologist, Leiden University Medical Centre

The current COVID-19 vaccination campaign involves injecting the vaccine into muscle tissue, but injecting a smaller amount of vaccine in the skin might also provide good protection. A crowdfunding campaign has enabled Dutch infectious disease specialist Anna Roukens MD, PhD,  at the Leiden University Medical Centre (LUMC) to examine the safety and efficacy of vaccination delivery via the skin. It is the first research project of its kind worldwide, and it could have significant impact on managing the pandemic, because up to five times as many people may be vaccinated with the same amount of vaccine. The funding by the crowdfunding campaign not only facilitated an extension to the laboratory of professor of Virology Eric Snijder in Leiden, but has also enabled a great deal more coronavirus research to be conducted. In April, Anna Roukens,  has begun research on Moderna vaccine delivery via the skin.

Rabies and yellow fever

Intradermal or skin vaccination is a form of vaccination where the vaccine is delivered in a specific layer of the skin. Even though vaccines are most often injected into muscle tissue (typically into the upper arm), skin vaccination can be applied to vaccinations for certain infections, such as rabies and yellow fever. Thus far however, skin vaccination has hardly ever been tried out with mRNA-vaccines.

Dendritic cells

Skin vaccination specifically triggers the dendritic cells within the skin. These cells are capable of processing antigen material and present this to the T-cells of the immune system. Once the dendritic cells become activated, they migrate to the lymph nodes where they interact with T-cells and B-cells to initiate and shape an adaptive immune response.

Roukens explains the rationale behind the research at LUMC. “A huge problem is that there are currently not enough supplies to vaccinate everyone at the same time. With skin vaccination, we can vaccinate more people using the same amount of vaccine. This means people could get vaccinated sooner. Skin vaccination introduces a small amount of the vaccine to the dendritic cells within the skin. These are capable of processing the vaccine in a very efficient manner, triggering a powerful immune response from the T-cells. Ensuring delivery precisely to the dendritic cells means no vaccine gets wasted.”

More precision required

If skin vaccination saves so much vaccine, then why isn’t this method more universally applied?

Roukens: “Intramuscular vaccination uses more vaccine, but this is really only an issue when a vaccine is either very expensive, or whether there is a shortage and no way to ramp up vaccine fabrication, which is basically the scenario we are facing now. Also, intramuscular vaccination is easier and faster to administer. Skin vaccination requires a more precise administration.”

She continues: “We now want to find out whether the Moderna vaccine is also suitable for immunisation via the skin. We first plan to test its safety and will then work out how much vaccine is needed to provide good protection.” The choice for Moderna was made because Moderna has tested intradermal vaccination with one of their influenza mRNA-vaccines before.1 Also, the LUMC had doses of the vaccine available. It is normally very difficult to obtain vaccines for research, especially when a vaccine is in high demand as now is the case with the COVID-19 vaccines. If our small-scale tests go well, we will scale up our research, and we have asked the RIVM (the Dutch health authority) if more Moderna vaccine doses can be made available to that end.”

Mid-april, in-person testing with skin vaccination started on a small scale. Roukens: “Ten volunteers were inoculated with just 10% of the normal dosage, in order to establish whether skin vaccination of an mRNA vaccine did not cause any side effects. This was not the case, so a second phase of the trial is underway, in which 15 volunteers will receive 20% of the normal intramuscular dosage. “If these tests go well, we will commence a larger trial. Hopefully we will have our first results before summer.”

Tackling the pandemic

That might be too late for the Netherlands or Belgium where vaccinations are in full swing, and where the governments strive to have everyone who so chooses can be vaccinated before August. “We do not know whether our results will be available before the end of the vaccination campaigns. What we do expect, however, is more frequent coronavirus outbreaks. Moreover, almost no vaccines have been administered in poor countries yet. So we are definitely not done with vaccinations yet. If intradermal vaccination with the Moderna vaccine is effective, it may prove to be an important step in tackling the pandemic.”


1. Feldman RA, Fuhr R, Smolenov I, et al. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine;2019 May 31;37(25):3326-3334. doi: 10.1016/j.vaccine.2019.04.074. Epub 2019 May 10.

2. Clinical trials register information on the LUMC trial ‘Establishing the safety, tolerability and immunogenicity of intradermal delivery of mRNA SARS-CoV-2 vaccine in healthy adults’: