On July 6, 2022 Elicio Therapeutics, a clinical stage biotechnology company developing a pipeline of novel immunotherapies for the treatment of cancer and other diseases, reported that it presented preclinical data demonstrating its Amphiphile (AMP) platform adjuvant AMP-CpG combined with cell surface-associated viral protein EBV gp350 and EBVpoly protein, elicits a robust and durable immune response to Epstein-Barr virus (EBV) (Press release, Elicio Therapeutics, JUL 6, 2022, View Source [SID1234616503]). EBV gp350 is expressed on the outside of the virus and on the cells producing the virus, making it a major target for neutralizing antibodies and CD4+ T cells, while EBVpoly protein contains multiple epitopes for CD8+ T cells. The data was presented at the 2022 Keystone Symposia on Viral Immunity Basic Mechanisms and Therapeutic Applications virtually and in-person at the Keystone Resort in Keystone, CO from June 29-July 2, 2022. The electronic poster is accessible here.

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EBV is a herpesvirus responsible for the well-known mononucleosis infections ("mono") and has also been implicated in multiple lymphoid and epithelial cancers. EBV targets both B cells and epithelial cells and utilizes their molecular machinery to replicate the viral genome. The virus causes B cells to differentiate into memory B cells, which then can move into the circulatory system, or become latent until a trigger causes reactivation. Approximately 95%[1] of the adult population worldwide is infected with EBV which persists for the life of the individual, however, there is currently no approved vaccine.

"Vaccines against EBV have historically been difficult to develop because of the associated viral latency, persistence and immune modulation properties which enable it to evade effective antibody targeting," said Lisa McNeil, Ph.D., Head of Translational Medicine at Elicio Therapeutics. "These data reinforce what we’ve seen in previous studies with our AMP platform, demonstrating the potent and durable immune responses elicited by delivering a therapeutic payload direct to the lymph nodes, the control center of the immune system. By targeting the most abundant glycoprotein expressed on the virus with the AMP-CpG adjuvant, in a mouse model mimicking human-specific immune responses to viral infection, we were able to induce neutralizing antibodies and strong T cell responses. This holds great promise for prevention of EBV associated diseases and controlling the spread of latently infected B cells."

The EBV vaccine is based on the research of Dr. Rajiv Khanna, Professor, Senior Scientist and Coordinator of QIMR Berghofer’s Centre for Immunotherapy and Vaccine Development. Professor Khanna said, "I am encouraged by the data demonstrating the potential of the AMP-CpG adjuvant combined with the EBV proteins to not only activate but supercharge the immune system as shown by the high frequencies of polyfunctional gp350-specific CD4+ T cells and EBVpoly-specific CD8+ T cells induced in this model."

Poster Presentation Details

Title: A Lymph Node Targeted Engineered Subunit Antigen and Molecular Adjuvant Vaccine Promotes Potent Cellular and Humoral Immunity to Epstein Barr Virus in HLA-expressing Mice

Highlights from the Poster

EBVpoly is a polyepitope protein developed at QIMR Berghofer Medical Research Institute that includes 20 CD8+ T cell epitopes from EBV latent and lytic antigens with broad coverage against multiple HLA types.
AMP-CpG delivers adjuvant directly to lymph nodes, boosting the immune response to protein antigens.
Vaccination with AMP-CpG combined with EBV gp350 and EBVpoly proteins rapidly induced potent gp350-specific IgG and EBV neutralizing antibody responses in HLA transgenic mice.
AMP-CpG immunization induced high frequencies of polyfunctional gp350-specific CD4+ T cells and EBVpoly-specific CD8+ T cells.
The potent humoral and cellular immunity induced by AMP-CpG was durable, with responses maintained for >7 months.
The broad coverage against multiple viral determinants and the AMP-CpG adjuvant are likely to provide better protection against primary EBV infection while the strong T cell responses will be critical in controlling the spread of latently infected B cells and the development of EBV-associated diseases, such as malignancies and multiple sclerosis.
About the Amphiphile Platform

Our proprietary Amphiphile, or AMP, platform delivers investigational immunotherapeutics directly to the "brain center" of the immune system – the lymph nodes. We believe this site-specific delivery of disease-specific antigens, adjuvants and other immunomodulators may efficiently educate, activate and amplify critical immune cells, potentially resulting in induction and persistence of potent adaptive immunity required to treat many diseases. In preclinical models, we have observed lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function and durability. We believe our AMP lymph node-targeted approach will produce superior clinical benefits compared to immunotherapies that do not engage the lymph nodes.

Our AMP platform, originally developed at the Massachusetts Institute of Technology, or MIT, has broad potential across cancers, infectious diseases and other disease indications to advance a number of development initiatives through internal activities, in-licensing arrangements or development collaborations and partnerships.

The Amphiphile platform is thought to deliver immunotherapeutics directly to the lymph nodes by latching on to the protein albumin, found in the bloodstream, as it travels to lymphatic tissue. In preclinical models, we have observed lymph node-specific engagement driving therapeutic immune responses of increased magnitude, function and durability.