VIU-1005

The ongoing SARS-CoV-2 pandemic continues to be a major health burden globally, especially in resource-limited areas. Continued research into more effective and accessible vaccines is required to reduce the burden of disease. Here, we use an emerging vaccine delivery system, the high-density microarray patch (HD-MAP) to deliver a plasmid DNA vaccine (Delta 6P) encoding for the SARS-CoV-2 spike protein. HD-MAP delivery of this vaccine resulted in robust IgG responses in mice against multiple domains of the spike protein. The cellular response to vaccination was also measured, and comparative analysis showed that relative to intramuscular vaccination, HD-MAP vaccination elicited spike-specific CD4⁺ T and CD8⁺ T cell responses that were largely comparable, but the number of polyfunctional CD4⁺ T cells was higher in the HD-MAP group. Collectively, this work suggests that HD-MAP delivery of the Delta 6P vaccine is effective against SARS-CoV-2, warranting further investigation.

SARS-CoV-2 spike-based vaccines are used to control the COVID-19 pandemic. However, emerging variants have become resistant to antibody neutralization and further mutations may lead to full resistance. We tested whether T cells alone could provide protection without antibodies. We designed a T cell-based vaccine in which SARS-CoV-2 spike sequences were rearranged and attached to ubiquitin. Immunization of mice with the vaccine induced no specific antibodies, but strong specific T cell responses. We challenged mice with SARS-CoV-2 wild-type strain or an Omicron variant after the immunization and monitored survival or viral titers in the lungs. The mice were significantly protected against death and weight loss caused by the SARS-CoV-2 wild-type strain, and the viral titers in the lungs of mice challenged with the SARS-CoV-2 wild-type strain or the Omicron variant were significantly reduced. Importantly, depletion of CD4+ or CD8+ T cells led to significant loss of the protection. Our analyses of spike protein sequences of the variants indicated that fewer than one-third presented by dominant HLA alleles were mutated and that most of the mutated epitopes were in the subunit 1 region. As the subunit 2 region is conservative, the vaccines targeting spike protein are expected to protect against future variants due to the T cell responses.