Next-Generation Lymph Node Targeting COVID-19 Vaccine Promises Enduring T Cell Immunity

A next-generation lymph node targeting COVID-19 vaccine has demonstrated a unique ability to elicit a high magnitude T Cell response to the SARS-CoV-2 virus along with potent neutralizing antibody induction in preclinical studies.

Since antibody responses to the SARS-CoV-2 virus are short-lived, balanced responses including potent and long-lived antiviral T cells could result in durable protection following the administration of ELI-005, a protein subunit vaccine for COVID-19 developed by Elicio Therapeutics (Cambridge, MA, USA). ELI-005 has two components. The first is ELI-004, an Amphiphile adjuvant containing a hydrophobic albumin-binding lipid linked to a hydrophilic immune stimulating CpG DNA oligonucleotide (AMP-CpG). This design achieves efficient lymph node targeting by the association AMP-CpG with tissue albumin after injection, since albumin naturally flows into nodes carrying AMP-CpG. The second component is the COVID-19 Spike protein receptor binding domain (RBD), which prior studies have shown to be a target of T cell and neutralizing coronavirus antibody responses.

The study showed that the ELI-005 vaccination with COVID-19 Spike RBD protein and ELI-004 (AMP-CpG) given at two-week intervals led to parallel responses balanced across both antibody and T cell mechanisms. Up to 25-fold higher numbers of T cells than benchmark vaccines were detected in peripheral blood (>40% of CD8) and sites that provide the first line of defense against COVID-19 including lung tissue (>70% CD8) and respiratory fluid. The ELI-005 vaccination induced 265-fold higher neutralizing antibody responses to coronavirus proteins than were present in convalescent COVID-19 patients Multifunctional CD4+ and CD8+ T cells reached the lung and were secreted into the respiratory fluid that provides the first line of defense against COVID-19. When aged mice were compared to younger animals, potent antibody and T cell responses were maintained. There was no sign of risk for vaccine-associated enhanced respiratory disease (VAERD). Since up to 10-fold dose-reduction of the COVID-19 protein component of ELI-005 maintained the immune response, correspondingly lower manufacturing effort would be needed to provide vaccine access for widespread application.

“Low T cell responses are a major challenge for COVID-19 vaccine development, and antibody response to natural infection is short-lived,” said Christopher Haqq, M.D., Ph.D., Elicio’s Executive Vice President, Head of Research and Development, and Chief Medical Officer. “We are excited to report that ELI-005 gave potent T cell responses alongside antibody induction 265-fold higher than in recovering COVID-19 patients. The completed GMP manufacturing and toxicology studies for ELI-004 in Elicio’s ELI-002 vaccine for KRAS driven cancers should facilitate rapid clinical translation for ELI-005.”

“Ten-fold reduction in the amount of COVID-19 antigen required for the ELI-005 vaccine may help efforts to deploy vaccination broadly,“ said Peter DeMuth, Ph.D., Elicio’s Founding Scientist and Vice President of Research. “The responses observed in aged mice are also compelling because they suggest the possibility to protect the elderly, particularly nursing home residents who suffer disproportionately from COVID-19.”

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Elicio Therapeutics