The ongoing coronavirus disease 2019 (COVID-19) pandemic continues to disrupt essential health services in 90 percent of countries today. The spike (S) protein found on the surface of the causative agent, the SARS-CoV-2 virus, has been the prime target for current vaccine research since antibodies directed against the S protein were found to neutralize the virus. However, as new variants emerge, mutations within the spike protein have given rise to potential immune evasion of the response generated by the current generation of SARS-CoV-2 vaccines. In this study, a modified, HexaPro S protein subunit vaccine, delivered using a needle-free high-density microarray patch (HD-MAP), was investigated for its immunogenicity and virus-neutralizing abilities. Mice given two doses of the vaccine candidate generated potent antibody responses capable of neutralizing the parental SARS-CoV-2 virus as well as the variants of concern, Alpha and Delta. These results demonstrate that this alternative vaccination strategy has the potential to mitigate the effect of emerging viral variants.

Pandemic preparedness requires vaccine platforms that are fast to produce, thermostable and suitable for broad deployment. DNA vaccines are well suited to this task but have historically suffered from poor immunogenicity when delivered by conventional intramuscular (IM) injection. Here, we evaluated high-density microarray patch (HD-MAP) delivery of a DNA vaccine encoding the influenza A/California/01/2009 (H1N1pdm09) haemagglutinin (HA) antigen. In vivo imaging of a luciferase reporter construct demonstrated earlier and higher expression following HD-MAP application compared to IM injection. HD-MAP delivery of the HA vaccine induced strong HA-specific IgG responses, whereas IM delivery did not. Upon challenge with a homologous H1N1 virus, all HD-MAP-vaccinated mice were protected from weight loss, while 50% of intramuscularly vaccinated mice met humane endpoints. These findings support the use of HD-MAPs to overcome delivery limitations of DNA vaccines and enhance their utility for future outbreak and pandemic response.