Type: Vaccine based on Heat’s gp96 platform, designed to induce a multi-epitope specific memory CD8 T-cell response that protects against multiple, distinct coronavirus strains and against potential future mutations of SARS-CoV-2 and other coronaviruses. The vaccine is secreted from allogeneic cells expressing full-length protein S.
Status: Researchers from Heat and the University of Miami on August 24 posted a preprint at bioRxiv reporting positive preclinical results for gp96-Ig-S. The vaccine effectively stimulated a robust cellular immune response against protein S, and generated powerful, protein S polyepitope-specific CD4+ and CD8+ T cell responses in both lung interstitium and airways.
Specifically, gp96-Ig-S significantly increased the frequency of systemic and tissue-specific CD8+ T-cells by conferring cellular immunity; primed potent effector memory CD8+ T cell responses and tissue resident memory CD8+ T cells localized in the lungs; and elicited a robust immune response directed against the Spike protein of SARS-CoV-2, generating both helper CD4+ T-cells and cytotoxic CD8+ T cells.
The vaccine also induced the secretion of cytokines (IFN-gamma, IL-2, TNF-alpha) from CD8+ and CD4+ T cells in both the spleen and lungs, and induced high frequencies of S-protein specific (against S1 and S2 epitopes) CD8+ T cells in the respiratory airways of human leukocyte antigen (HLA)-A2-02-01 transgenic mice—“providing encouraging translational data that the vaccine is likely to work in humans,” the researchers wrote.”
“Our COVID-19 vaccine is designed to drive predominantly T cell immunity along with antibody responses and innate immunity. As a result, we believe our vaccine has the potential to be used as either a standalone vaccine, or in combination with these other approaches to enhance efficacy,” Heat CEO Jeff Wolf said in a statement released August 13.
In July, Heat said its COVID-19 vaccine showed in-vivo proof-of-concept of immunogenicity in animal models, including expansion of human-HLA-restricted T-cells against immunodominant epitopes of SARS-CoV-2 Spike protein. Testing demonstrated expansion of antibody-supporting CD4+, and virus killing CD8+ T-cells in the lungs of the animals.
In addition, stimulation of anti-viral killer CD8+ T-cells in human HLA-A2-positive transgenic mice provides encouraging pre-clinical data to support human trials, stated Natasa Strbo MD, DSc, Assistant Professor of Microbiology and Immunology at the University of Miami Miller School of Medicine and co-developer of Heat’s gp96 platform.
In May, Heat said it will partner with Waisman Biomanufacturing, part of the University of Wisconsin, to manufacture Heat’s COVID-19 vaccine for preclinical testing planned for this quarter, as well as a planned Phase I trial. Earlier in May, Heat said it was applying for grants to support clinical development of the vaccine, and was advancing collaboration discussions
In March, Heat said it will collaborate with University of Miami Miller School of Medicine to develop a proprietary UM COVID-19 point-of-care diagnostic test—more than two weeks after the partners agreed to develop a vaccine targeting SARS-CoV-2.
Heat says its approach is designed to activate a potent immune response, without the potential for genomic integration of foreign DNA or viral vector instability possible with attenuated viral vaccines. The company has cited the antiviral activity in the lungs generated in its NIH- and U.S. Department of Defense (DOD)-funded mice and primate trials, in which it used its gp96 platform to generate vaccines against SIV/HIV, malaria, zika and other infectious diseases.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: