PepTC Vaccines Publishes Positive Preclinical Results for COVID-19 Peptide Vaccine That Shows ...
LONDON, Oct. 19, 2020 (GLOBE NEWSWIRE) -- PepTC Vaccines Limited, a subsidiary of Treos Bio Limited, today announced the publication of positive preclinical results of its investigational PolyPEPI-SCoV-2 peptide vaccine. The study was published on the preprint service bioRxiv website at https://www.biorxiv.org/content/10.1101/2020.10.16.339937v1 and has been submitted for publication in a peer-reviewed journal.
Scientists at PepTC Vaccines and its parent Treos Bio reported that PolyPEPI-SCoV-2 vaccine administered with Montanide ISA 51VG adjuvant was safe in two mouse models and elicited highly specific, TH1-biased CD8+ and CD4+ T cell responses against all four structural proteins of the virus. PolyPEPI-SCoV-2 vaccination also induced humoral responses, as measured by total mouse IgG for BALB/c and human IgG for CD34+ humanized mouse models. Binding antibodies can act in cooperation with the vaccine-induced CD8+ killer T cells against viral reservoirs to help rapid viral clearance.
Importantly, the study also showed that PolyPEPI-SCoV-2 defines natural CD8+ and CD4+ T cell responses observed in asymptomatic / mild COVID-19 patients one to five months after symptom onset. In tests of blood samples from 17 donors the PolyPEPI-SCoV-2-specific CD8+ T cell repertoire used for recovery from COVID-19 was extremely diverse: donors recognized on average seven different vaccine peptides out of nine; 87 percent of donors had multiple vaccine-specific T cells against three SARS-CoV-2 structural proteins and 53 percent against all four.
Most vaccine candidates currently in advanced clinical testing are using neutralizing antibody-focused technologies. However, the lessons learned from the SARS epidemic and COVID-19 convalescents indicate that while these vaccines may achieve transient protection, long-term control mediated by T cells is unlikely when only the spike of the virus, but no other structural proteins are targeted.
“The large majority of the SARS-CoV-2 vaccines currently under clinical development target only the spike protein of the virus,” said Eniko R. Toke, Ph.D., corresponding author on the study and Chief Scientific Officer of Treos Bio, who noted that the blood samples revealed that only 36 percent of convalescents’ PolyPEPI-SCoV-2 specific immunity was directed against the spike protein. The remaining 64 percent was almost equally distributed among the other structure proteins of the virus. “That suggests spike-protein based competitive vaccines may not harness the full potential of humans’ anti-SARS-CoV-2 immunity,” she said.
Peptide-based vaccines have had limited success to date, due in part to the lack of knowledge regarding the selection of immunogenic peptides. In the paper, the authors argue that such uncertainty is reduced by an understanding of how an individual’s genetic background responds to specific peptides.
PolyPEPI-SCoV-2 consists of nine synthetic peptides. The vaccine targets the four structural proteins of the SARS-CoV-2. PepTC Vaccine’s scientists designed the vaccine using PepTC’s parent Treos Bio’s T cell vaccine development platform. This is the same platform used by Treos Bio to develop its lead investigational clinical candidate PolyPEPI-1018, a precision vaccine to treat metastatic colorectal cancer. Treos Bio’s platform technology determines the best antigen targets for a specific disease or pathogen, but also makes a computational determination of the antigens to which the immune systems of individuals in large cohorts can respond.
In the case of SARS-COV-2, this can have significant implications for how people of different ethnicities respond to the vaccines. The disease course varies based on genetic diversity represented by race. Increased risk of infection as well as worse clinical outcomes are associated with people who are Black, Asian, or other non-Caucasian ethnic groups.
In silico testing of the PolyPEPI-SCoV-2 vaccine in diverse ethnic groups of 16,000 HLA genotyped subjects from a U.S. bone marrow donor database, resulted in an equally high proportion of subjects showing both CD8+ and CD4+ T cell responses against multiple peptides in each of 16 ethnic groups. PolyPEPI-SCoV-2 is predicted to produce a multi-antigenic immune response in more than 98 percent of subjects, globally.
“We are addressing the challenges of the heterogeneity of individuals’ immune response, the potential for structural variations in the infecting virus, and the observed phenomenon of long-term immunity to coronaviruses likely stemming from T cell activity,” said Dr. Christopher C. Gallen, Executive Chairman of PepTC’s parent Treos Bio. “Based on our clinical experience with our PolyPEPI peptide immunotherapy in metastatic colorectal cancer patients and our validated in silico human model, we believe that our approach has the potential to provide a broad and long-lasting immune response, independent of gender, age, or ethnicity, and be able to protect people worldwide against COVID-19.”
PepTC Vaccines expects to advance to human clinical studies for its investigational PolyPEPI-SCoV-2 vaccine during the fourth quarter of 2020. Pre-IND regulatory confirmations were obtained from FDA (US), MHRA (UK) and PEI (Germany). PepTC Vaccines expects to have preliminary trial results in the spring of 2021.
About Treos Bio Limited
Treos Bio, headquartered in London, uses data science and proprietary biomarkers to develop its precision peptide cancer immunotherapies, with substantially shortened development timelines and at low costs. Treos Bio’s off-the-shelf cancer immunotherapies are designed to exclude autoimmunity and to induce tumor-specific immune responses to be safer and more effective in patients who do not benefit from current immunotherapies. Treos’ novel biomarkers support the development of in vitro companion diagnostic tests to identify patients who are most likely to respond to treatment. The company is in clinical development of its PolyPEPI-1018 immunotherapy for metastatic colorectal cancer. It presented positive results from a Phase I/II study performed at the Mayo Clinic and at the University of Pisa in a poster presentation at ASCO in May 2020. It has also completed preclinical development of additional members of the PolyPEPI cancer immunotherapy family with companion diagnostics to select likely responders. These off-the-shelf therapies are designed for a general population of patients with ovarian-, breast-, bladder-, gastric- and lung cancers and melanoma. Treos’ patient-focused immunotherapy design also supports the development of immunotherapies for single individuals as well as for a defined population of individuals with a specific genetic background. More information can be found at www.treosbio.com.
About PepTC Vaccines Limited
PepTC Vaccines, a subsidiary of Treos, is focused on developing a broad and long-lasting global vaccine for COVID-19 (SARS-CoV-2). Patent applications have been filed on the PolyPEPI-SCoV-2 vaccine composition in April 2020. GMP manufacturing of 4,000 doses of PolyPEPI-SCoV-2 was completed in September 2020.PepTC Vaccines is progressing with a funding round to finance the Phase 1 and 2 clinical testing of PolyPEPI-SCoV-2. It anticipates commencing human clinical trials in the fourth quarter of 2020. More information can be found at www.peptc.com.
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