A proprietary lymph node targeting adjuvant for COVID-19 has elicited high magnitude T cell responses alongside potent neutralizing antibody induction; the studies are published in the February 5 issue of Science Advances. Significantly, the magnitude of T cell responses substantially exceeded prior observations in mouse models with benchmark COVID-19 vaccines.
ELI-005, Elicio Therapeutics’ novel SARS-CoV-2 vaccine, has two components. The first is ELI-004, an Amphiphile (AMP) adjuvant containing a hydrophobic albumin-binding lipid linked to a hydrophilic immune stimulating CpG DNA oligonucleotide (AMP-CpG). This design achieves unprecedented efficiency in lymph node targeting as a result of AMP-CpG binding to tissue albumin after injection, leading to the complex flowing through lymphatics into nodes and delivering the immunogenic AMP-CpG payload directly to key immune cells. 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 B cell mediated neutralizing coronavirus antibody responses in humans.
Highlights of the research in Science Advances include:
- Up to 25-fold higher numbers of T cells than benchmark vaccines 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
- Induction of 265-fold higher neutralizing antibody responses to coronavirus protein antigens than were present in convalescent COVID-19 patients
- Durable responses with no decline in T cell or antibody levels 6 weeks after completion of the vaccine regimen
- Consistent potency in aged as well as young mice
- Dose sparing potential with 10-fold lower doses of the viral protein antigen needed to generate potent immune responses
Inside lymph nodes, key crosstalk occurs between cells presenting vaccine antigens and the T and B cells that carry out the immune response. Therefore, AMP adjuvants may promote the effectiveness of communication between immune cells resulting in improved vaccine responses including enhanced magnitude and functionality. Importantly, the generation of T cell responses, through potent immune activation in the lymph nodes may provide critical breadth of response to allow for extended immune memory, more robust protection against newly emerging viral variants, and favorable durability of response which have been associated with T cell mediated protection in the event of waning antibody levels.
“These proof-of-concept findings that AMP adjuvants improve vaccine responses open the door to develop improved, more durable treatments for infectious diseases and cancers. The dose-sparing effect could reduce the amount of material needed, speeding availability for population-wide COVID-19 immunization. Also exciting, the favorable storage conditions could simplify vaccine distribution by eliminating a need for freezers. Completed manufacturing of ELI-004 AMP-CpG adjuvant will facilitate rapid advancement of ELI-005 into clinical trials,” said Christopher Haqq, M.D., Ph.D., Elicio’s Executive Vice President, Head of Research and Development, and Chief Medical Officer.
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 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 IND application.
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 and immunology, with years of vaccine research, 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, ELI-002, targeting KRAS-driven cancers will begin initial patient studies in solid tumor patients in the first half of 2021. 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.wpengine.com.
Elicio Therapeutics: Merina Zeller, 617-482-0042, firstname.lastname@example.org