Tag Archives: Shaomin Tian

Microneedle vaccine patch outperforms needle

Vaccine patch sounds a lot friendlier than ‘needle’ and in the hoopla about vaccine hesitation I have to wonder if the fact that some people don’t like or are deeply fearful of needles is being overlooked.

Perhaps this or some other vaccine patch* will be ready for use in time for the next pandemic. From a September 24, 2021 news item on ScienceDaily,

Scientists at Stanford University and the University of North Carolina [UNC] at Chapel Hill have created a 3D-printed vaccine patch that provides greater protection than a typical vaccine shot.

The trick is applying the vaccine patch directly to the skin, which is full of immune cells that vaccines target.

The resulting immune response from the vaccine patch was 10 times greater than vaccine delivered into an arm muscle with a needle jab, according to a study conducted in animals and published by the team of scientists in the Proceedings of the National Academy of Sciences [PNAS].

A September 23, 2021 University of North Carolina at Chapel Hill news release (also on EurekAlert but published Sept. 24, 2021), which originated the news item, describes the patch in greater detail (Note: Links have been removed),

Considered a breakthrough are the 3D-printed microneedles lined up on a polymer patch and barely long enough to reach the skin to deliver vaccine.

“In developing this technology, we hope to set the foundation for even more rapid global development of vaccines, at lower doses, in a pain- and anxiety-free manner,” said lead study author and entrepreneur in 3D print technology Joseph M. DeSimone, professor of translational medicine and chemical engineering at Stanford University and professor emeritus at UNC-Chapel Hill.

The ease and effectiveness of a vaccine patch sets the course for a new way to deliver vaccines that’s painless, less invasive than a shot with a needle and can be self-administered. 

Study results show the vaccine patch generated a significant T-cell and antigen-specific antibody response that was 50 times greater than a subcutaneous injection delivered under the skin

That heightened immune response could lead to dose sparing, with a microneedle vaccine patch using a smaller dose to generate a similar immune response as a vaccine delivered with a needle and syringe.

While microneedle patches have been studied for decades, the work by Carolina and Stanford overcomes some past challenges: through 3D printing, the microneedles can be easily customized to develop various vaccine patches for flu, measles, hepatitis or COVID-19 vaccines.

Advantages of the vaccine patch

The COVID-19 pandemic has been a stark reminder of the difference made with timely vaccination. But getting a vaccine typically requires a visit to a clinic or hospital.

There a health care provider obtains a vaccine from a refrigerator or freezer, fills a syringe with the liquid vaccine formulation and injects it into the arm.

Although this process seems simple, there are issues that can hinder mass vaccination – from cold storage of vaccines to needing trained professionals who can give the shots.

Meanwhile vaccine patches, which incorporate vaccine-coated microneedles that dissolve into the skin, could be shipped anywhere in the world without special handling and people can apply the patch themselves.

Moreover, the ease of using a vaccine patch may lead to higher vaccination rates.

How the patches are made

It’s generally a challenge to adapt microneedles to different vaccine types, said lead study author Shaomin Tian, researcher in the Department of Microbiology and Immunology in the UNC School of Medicine.

“These issues, coupled with manufacturing challenges, have arguably held back the field of microneedles for vaccine delivery,” she said.  

Most microneedle vaccines are fabricated with master templates to make molds. However, the molding of microneedles is not very versatile, and drawbacks include reduced needle sharpness during replication.

“Our approach allows us to directly 3D print the microneedles which gives us lots of design latitude for making the best microneedles from a performance and cost point-of-view,” Tian said.

The microneedle patches were 3D printed at the University of North Carolina at Chapel Hill using a CLIP prototype 3D printer that DeSimone invented and is produced by CARBON, a Silicon-Valley company he co-founded.

The team of microbiologists and chemical engineers are continuing to innovate by formulating RNA vaccines, like the Pfizer and Moderna COVID-19 vaccines, into microneedle patches for future testing.

“One of the biggest lessons we’ve learned during the pandemic is that innovation in science and technology can make or break a global response,” DeSimone said. “Thankfully we have biotech and health care workers pushing the envelope for us all.”

Additional study authors include Cassie Caudill, Jillian L. Perry, Kimon lliadis,  Addis T. Tessema and Beverly S. Mecham of UNC-Chapel Hill and Brian J. Lee of Stanford.  

Here’s a link to and a citation for the paper,

Transdermal vaccination via 3D-printed microneedles induces potent humoral and cellular immunity by Cassie Caudill, Jillian L. Perry, Kimon Iliadis, Addis T. Tessema, Brian J. Lee, Beverly S. Mecham, Shaomin Tian, and Joseph M. DeSimone. PNAS September 28, 2021 118 (39) e2102595118; DOI: https://doi.org/10.1073/pnas.2102595118

This paper appears to be open access.

*I have featured vaccine patches here before, this December 16, 2016 post (Australia’s nanopatch: a way to eliminate needle vaccinations) is one of many stretching back to 2009.

Nanotechnology-enabled dengue virus vaccine

Here’s news of work-in-progress for a dengue virus vaccine and, possibly, a Zika virus vaccine too. From a Nov. ??, 2016 University of North Carolina news release,

Scientists at the UNC School of Medicine are working to develop a nanoparticle vaccine to protect against the four serotypes of dengue virus, which infects more than 350 million people across the globe each year.

Aravinda de Silva, PhD, professor of microbiology and immunology, and a post-doctoral researcher Stefan Metz, PhD, recently published the latest on their vaccine development efforts in PLOS Neglected Tropical Diseases.

The nanoparticle platform was produced with PRINT (Particle Replication in Non-wetting Templates) technology. Joseph DeSimone, PhD, the Chancellor’s Eminent Professor of Chemistry and a joint professor in the Department of Pharmacology at UNC, developed PRINT, a nano-molding technique, in 2004.

Rather than using a killed or attenuated virus to develop a vaccine for dengue, de Silva’s lab is focusing on “expressing the E protein and attaching it to nanoparticles to induce good immune responses,” Metz said.

The nanoparticle vaccine platform can be safer to certain populations than vaccines that use either live or killed virus, he said.

One of the many complexities about developing a successful dengue vaccine, Metz explained, is that there are four serotypes of the virus, which means researchers need to develop a vaccine that provides immunity against all four serotypes.

“There are currently several vaccines in trial and development for dengue,” Metz said. “One vaccine has gone through all three clinical trial phases and has been licensed in some countries. Although these vaccines produce good antibody responses, a large part of the population still wasn’t protected from each of the serotypes.

“With dengue, you need to vaccinate people against all four serotypes at once in order to protect people. That’s why we’re combing the different serotypes.”

In their most recent study, de Silva and Metz focused their efforts on the second serotype. Now, they’re moving forward with the same studies for serotypes one, three and four.

“In the study, we express the E protein, which is found on the surface of the virus particle,” Metz explained. “This protein is organized in a very complex way, and this complex organization exposes isotopes that are important to induce protective immune response.”

De Silva and Metz were recently named to a global research consortium to tackle Zika, and they’re using the same nanoparticle vaccine platform as they work to develop a Zika vaccine.

“Globally, if you look at the numbers, dengue is still a much bigger problem than Zika,” Metz said, noting that an estimated 25,000 people die from dengue infections each year. “If you get dengue, you might not even notice it. If you do get clinical symptoms during a first infection of dengue, you might feel like you have a feverish flu. A lot of people don’t even know it because if you’re not feeling well for a couple days, you don’t necessarily think that it’s caused by a dengue virus infection.

“However, if you were infected by the first serotype and you had a secondary infection with a different serotype, that’s when the more severe diseases can come up – stress syndromes, hemorrhagic diseases – those can be fatal diseases,” Metz said. “There are thousands and thousands of people dying from those diseases each year.”

Here’s a link to and a citation for the paper,

Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses by Stefan W. Metz, Shaomin Tian, Gabriel Hoekstra, Xianwen Yi, Michelle Stone, Katie Horvath, Michael J. Miley, Joseph DeSimone, Chris J. Luft, Aravinda M. de Silva. PLOS http://dx.doi.org/10.1371/journal.pntd.0005071  Published: October 20, 2016

This paper is open access.