Could laser-facilitated epicutaneous vaccination for SARS-CoV-2 be an alternative to intramuscular injection?

Common immunization routes for coronavirus disease 2019 (COVID-19) vaccine candidates range from intramuscular, nasal and oral to intradermal.

Now, scientists at the University of Salzburg and Pantec Biosolutions AG have developed a laser-facilitated epicutaneous immunization against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. The model has induced angiotensin-converting enzyme 2 (ACE2) blocking antibodies in mice.

The study, published on the pre-print bioRxiv* server, shows another potential effective route to administer vaccines against SARS-CoV-2, the virus that causes COVID-19. Finding more ways to introduce vaccines can help combat the pandemic.

Epicutaneous immunization

As the pandemic continues to spread, many countries have already rolled out their immunization plans. To date, there are about 251 vaccines developed against SARS-CoV-2 infection. Of these, 70 vaccines are undergoing human trials to determine safety and efficacy.

Most of the COVID-19 vaccines developed are administered intramuscularly, while others can be given orally, intradermally, subcutaneously, and intranasally.

Epicutaneous immunization involves the introduction of biological material, drugs, or vaccines into the skin by shallow and bloodless piercing with small needles.

Currently, immunization through the skin gained attention as an alternative to traditional vaccine routes such as intramuscular or subcutaneous injections. The researchers developed a generation of skin micropores using infrared laser beams. The method is painless and bloodless, which can overcome the cornified outermost skin barrier and deliver large molecules like biologicals.

The method has been tested recently in healthy human adults utilizing epicutaneous patches that contain recombinant pertussis toxin. It showed promise to stimulate recall antibody responses, which was akin to the response induced by an injection of a commercial diphtheria-tetanus-acellular pertussis vaccine adjuvanted with alum.

The study

In the study, the researchers investigated whether laser-facilitated epicutaneous immunization with recombinant SARS-CoV-2 S1 spike protein could stimulate antibody responses that can prevent the spike from binding with the human cell ACE2 receptor.

For adjuvant action, the researchers used LT-B and CpG, which are known to be the most effective in inducing immune responses after epicutaneous immunization.

The mice immunized with the SARS-CoV-2 spike S1 protein exhibited high titers of specific blood immunoglobulin G (IgG) in two independent experiments. The LT-B markedly elevated IgG levels.

Meanwhile, the mice vaccinated with CpG-ODN 1826 adjuvant manifested the highest antibody titers of all the clusters. When the team increased the interval between vaccinations, there is no significant effect on the level of antibody response. Further, the CpG induced a faster immune response.

The titers can be boosted 5-fold when using the LT-B and more than 10-fold by CpG-ODN 1826. The serum antibodies produced can inhibit the interaction between the spike protein and the ACE2 human receptor.

After testing the skin immunization method with certain adjuvants, like the LT-B, it promoted mucosal immune responses. This shows that skin-based immunization with SARS-CoV-2 spike S1 protein can also stimulate antibody responses in the respiratory tract, the site primarily targeted by SARS-CoV-2.

Apart from inducing ACE2 inhibitory antibodies, laser-assisted epicutaneous immunization prompted spike-specific T-helper cells, which could cause long-term memory responses. This means that the vaccine can protect against SARS-CoV-2 for long periods, reducing the risk of re-infection.

To date, there are more than 111.75 million cases of COVID-19 globally. Of these, 2.47 million have died.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Angela Betsaida B. Laguipo

Angela is a nurse by profession and a writer by heart. She graduated with honors (Cum Laude) for her Bachelor of Nursing degree at the University of Baguio, Philippines. She is currently completing her Master's Degree where she specialized in Maternal and Child Nursing and worked as a clinical instructor and educator in the School of Nursing at the University of Baguio.