COVID-19 is no longer a public health emergency of international concern, according to the World Health Organization, but the virus is still a threat. We also continue to see new regulatory milestones for COVID-19 tests as well as innovation around vaccine delivery.

Vaxxas' COVID-19 patch

A needle-free COVID-19 vaccine candidate delivered using a high-density microarray patch (HD-MAP) is showing promise in a phase I human trial, according to Brisbane, Australia-based Vaxxas. The core technology was initially developed at The University of Queensland.

The COVID-19 vaccine involves HD-MAP delivery of HexaPro, a second-generation version of the spike protein used in all major FDA approved COVID-19 vaccines, which was modified to be more stable and immunogenic than its predecessor, giving potential coverage of all known SARS-CoV-2 variants, the company said. The HD-MAP COVID-19 vaccine patches were well tolerated, with no serious or severe adverse events. Analysis of samples from day 28 show the HD-MAP COVID-19 vaccine increased relevant antibody levels by 8-fold on average, and the antibody responses indicated a dose dependent trend.

“We are very encouraged by the compelling early data and rapid progress of our needle-free COVID-19 vaccine candidate,” said Vaxxas CEO David L. Hoey. “We believe our patch-based delivery of a next generation spike protein has the potential to offer best-in-class protection against COVID-19 along with cost-effective distribution without the need for extensive refrigeration.”

The phase I clinical trial is designed to assess the safety, tolerability, and immunogenicity of the HD-MAP COVID-19 vaccine candidate in 44 healthy adults between the ages of 18 and 50, who have had three doses of an authorized COVID-19 vaccine prior to enrollment in this study, with the last dose at least four months prior to participating. The study was fully enrolled, and all participants have now completed the final step in the study. In addition to the above measured outcomes, the trial is also designed to gather signals related to antibody and T-cell responses, including mucosal responses, to dosing with the patch-delivered vaccine candidate.

Preclinical research published in Science Advances and Vaccine, undertaken with The University of Queensland and other collaborators, demonstrated that HexaPro delivered using Vaxxas’ HD-MAP resulted in enhanced virus neutralizing antibody and T-cell responses against all major variants of concern, including alpha, beta, gamma, delta, and omicron, when compared to needle and syringe vaccination with HexaPro.

Vaxxas' HD-MAP technology uses an ultra-high-density array of projections – invisible to the naked human eye – applied to the skin as a patch sitting inside a small applicator device. When applied to the skin, the patch delivers vaccine to the abundant immune cells immediately below the skin surface. This approach can enhance the efficiency and effectiveness of resulting immune responses of vaccines, according to the company.

Vaxxas uses dry-coating technology to apply an active and stable vaccine onto the projections which offers the potential to eliminate the need for vaccine refrigeration during storage and transportation – reducing the resource and logistics burden of maintaining the refrigerated “cold chain.” Ease of use of the HD-MAP could enable simplified administration, potentially encompassing self-administration.

To create the COVID-19 vaccine candidate, Vaxxas' HD-MAP is coated with HexaPro vaccine and integrated into a single-use applicator, ready-for-vaccination. HexaPro is a highly stabilized protein designed to mimic the structure of the spike protein on the surface of the coronavirus to train the human immune system to recognize and fight SARS-CoV-2 infection. HexaPro is the most advanced spike protein from UTA’s world-renowned vaccine development team.

In extensive laboratory testing published in PLoS Med, Vaxxas’ HD-MAP delivered vaccines have been shown to be stable and remain active when stored and transported at room temperature and demonstrate greater safety and protection, along with a potential for a lower dose, when compared to needle and syringe delivery of vaccine antigens, including the HexaPro SARS-CoV-2 spike protein.

Vaxxas has completed three human clinical studies with its HD-MAP involving more than 300 participants, demonstrating safety and enhanced immune response of vaccine administration by HD-MAP. Two additional human clinical studies with a further 200 participants are currently underway.

CEPI backs aVaxziPen device

Oslo, Norway-based Coalition for Epidemic Preparedness Innovations (CEPI) and Oxford, UK-based aVaxziPen, have joined forces to develop two new vaccines using aVaxziPen's needle-free vaccine delivery system. These vaccines, one based on proteins and the other on mRNA, aim to eliminate the need for frozen storage. By doing so, the organizations say they can enhance fair access to vaccines.

CEPI said it will initially invest up to $1.6 million to evaluate the stability, delivery, and preclinical effectiveness of mRNA and protein-based vaccines developed using aVaxziPen's platform. If successful, CEPI and aVaxziPen may continue their partnership by selecting vaccine candidates that meet vaccination needs in low- and middle-income countries for Phase 1 clinical trials.

"This collaboration is a significant step toward disrupting the vaccine market and expanding vaccine coverage worldwide, particularly in underserved populations," said Robin Cohen, chief business officer at aVaxziPen.

Currently, mRNA vaccines require freezing because their fragile mRNA molecules can easily degrade. Once thawed, these vaccines must be used quickly. Removing the need for frozen storage would make shipping, storing, and distributing mRNA vaccines much easier and more cost-effective, particularly in low-resource settings, according to CEPI and aVaxziPen. Although protein-based vaccines do not typically require frozen storage, they still need to be kept between 2-8°C. Developing a protein vaccine that remains stable at temperatures up to 40°C for at least 1-2 months would simplify the delivery of these vaccines, even in remote regions, the organizations noted.

aVaxziPen has developed a solid-dose vaccine delivery platform that addresses these challenges. The company's pen applicator device is designed to protect mRNA and proteins from degradation, potentially eliminating the need for frozen storage for mRNA vaccines and cold-chain storage for protein-based vaccines. The company said it achieves this through its unique solid-dose formulation technology, which creates a stable and reliable vaccine formulation.

The company also touts other advantages of its applicator device. The device does not require specialized medical training, and it is reusable for up to 1,000 doses, according to aVaxziPen.

"Our mission at CEPI is to ensure equitable access to vaccines," said Anand Ekambaram, executive director of manufacturing and supply chain at CEPI. "aVaxziPen's innovative vaccine delivery technology requires minimal training, reduces the need for expensive cold-chain storage, and facilitates easier distribution and administration. These innovations will help improve access to life-saving vaccines in resource-limited settings during future outbreaks or pandemics."