Preclinical data from a lymph node targeted COVID-19 vaccine candidate showed potent CD8 and CD4 T Cells in lung tissue and respiratory fluid
CAMBRIDGE, MA, USA I August 19, 2020 IElicio Therapeutics, a next generation immunotherapy company, today published results of preclinical studies of ELI-005, a protein subunit vaccine for COVID-19. Findings include a unique ability to elicit a high magnitude T Cell response to COVID-19 alongside potent neutralizing antibody induction. Since antibody responses to COVID-19 are short-lived, balanced responses including potent and long-lived antiviral T cells could result in durable protection following ELI-005 administration. ELI-005 research highlights:
- 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
- Induced 265-fold higher neutralizing antibody responses to coronavirus proteins than were present in convalescent COVID-19 patients
- No sign of risk for vaccine-associated enhanced respiratory disease (VAERD), with ELI-005 providing a Th1 T cell (interferon gamma, tumor necrosis factor alpha) and Th1 antibody (IgG2bc) response profile
- When aged mice were compared to younger animals, potent antibody and T cell responses were maintained;
- 10-fold lower doses of the viral protein antigen maintained potent immune responses, suggesting that ELI-005 could reduce the material needed for population wide COVID-19 immunization
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. 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. 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.”
About ELI-004:
ELI-004 (AMP-CpG) is an Amphiphile modified TLR-9 agonist. ELI-004 “hitchhikes” on endogenous albumin until it reaches antigen presenting cells in the draining lymph nodes to potently stimulate immune activation and support expansion of adaptive immune responses. ELI-004 has previously demonstrated at least 10-fold improved lymph node delivery, leading to substantially enhanced immune cell delivery and immune responses versus conventional CpG and other benchmark adjuvants. ELI-004 has demonstrated eradication and cures in multiple preclinical cancer models and activity against infectious diseases including HPV and, in this study, COVID-19. Elicio Therapeutics expects to file Investigational New Drug (IND) Applications for ELI-004 as part of their ELI-002 in 2020.
About Elicio Therapeutics
Elicio Therapeutics is advancing the Amphiphile technology across immunotherapy platforms to defeat cancers and infectious diseases. By combining expertise in materials science, immunology, and immuno-oncology, Elicio is engineering potent Amphiphile immunotherapies that precisely target and fully engage the lymph nodes, the site in our bodies where the immune response is orchestrated. Elicio is engineering lymph node targeted cell therapy activators, immunomodulators, adjuvants and vaccines for an array of aggressive cancers and infectious diseases. Elicio’s lead Amphiphile vaccine targeting KRAS-driven cancers will begin initial patient studies in solid tumor patients in 2020. The Amphiphile platform emerged from laboratories of Darrell Irvine, Howard Hughes Investigator and Professor of Biomedical Engineering in the Koch Institute of Integrative Cancer Research at MIT. For more information, please visit https://elicio.com.
SOURCE: Elicio Therapeutics
Post Views: 24
Preclinical data from a lymph node targeted COVID-19 vaccine candidate showed potent CD8 and CD4 T Cells in lung tissue and respiratory fluid
CAMBRIDGE, MA, USA I August 19, 2020 IElicio Therapeutics, a next generation immunotherapy company, today published results of preclinical studies of ELI-005, a protein subunit vaccine for COVID-19. Findings include a unique ability to elicit a high magnitude T Cell response to COVID-19 alongside potent neutralizing antibody induction. Since antibody responses to COVID-19 are short-lived, balanced responses including potent and long-lived antiviral T cells could result in durable protection following ELI-005 administration. ELI-005 research highlights:
- 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
- Induced 265-fold higher neutralizing antibody responses to coronavirus proteins than were present in convalescent COVID-19 patients
- No sign of risk for vaccine-associated enhanced respiratory disease (VAERD), with ELI-005 providing a Th1 T cell (interferon gamma, tumor necrosis factor alpha) and Th1 antibody (IgG2bc) response profile
- When aged mice were compared to younger animals, potent antibody and T cell responses were maintained;
- 10-fold lower doses of the viral protein antigen maintained potent immune responses, suggesting that ELI-005 could reduce the material needed for population wide COVID-19 immunization
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. 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. 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.”
About ELI-004:
ELI-004 (AMP-CpG) is an Amphiphile modified TLR-9 agonist. ELI-004 “hitchhikes” on endogenous albumin until it reaches antigen presenting cells in the draining lymph nodes to potently stimulate immune activation and support expansion of adaptive immune responses. ELI-004 has previously demonstrated at least 10-fold improved lymph node delivery, leading to substantially enhanced immune cell delivery and immune responses versus conventional CpG and other benchmark adjuvants. ELI-004 has demonstrated eradication and cures in multiple preclinical cancer models and activity against infectious diseases including HPV and, in this study, COVID-19. Elicio Therapeutics expects to file Investigational New Drug (IND) Applications for ELI-004 as part of their ELI-002 in 2020.
About Elicio Therapeutics
Elicio Therapeutics is advancing the Amphiphile technology across immunotherapy platforms to defeat cancers and infectious diseases. By combining expertise in materials science, immunology, and immuno-oncology, Elicio is engineering potent Amphiphile immunotherapies that precisely target and fully engage the lymph nodes, the site in our bodies where the immune response is orchestrated. Elicio is engineering lymph node targeted cell therapy activators, immunomodulators, adjuvants and vaccines for an array of aggressive cancers and infectious diseases. Elicio’s lead Amphiphile vaccine targeting KRAS-driven cancers will begin initial patient studies in solid tumor patients in 2020. The Amphiphile platform emerged from laboratories of Darrell Irvine, Howard Hughes Investigator and Professor of Biomedical Engineering in the Koch Institute of Integrative Cancer Research at MIT. For more information, please visit https://elicio.com.
SOURCE: Elicio Therapeutics
Post Views: 24
