Second-gen COVID vaccine in development
NANTES, France—Building on demonstrated success with a vaccine targeting non-small cell lung cancer, French biotech OSE Immunotherapeutics has developed a promising prophylactic approach to combat SARS-CoV-2. Their candidate, called CoVepiT, leverages the company’s expertise in increasing memory immune response activated by leukocytes, rather than harnessing an antibody response.
According to their paper “Tissue-resident memory CD8 T-cell responses elicited by single injection of a multi-target COVID-19 vaccine,” which was recently published on BioRxiv, the vaccine technology uses artificial intelligence algorithms to increase T memory cell responses.
Alexis Peyroles, CEO of OSE, says, “We are rapidly advancing our fight against COVID-19, a major public health issue, with a vaccine program especially designed for people at risk, including older adults and immunocompromised populations. Initial preclinical results were strengthened by a parallel human ex-vivo study conducted in two clinical centers. Based on [this] positive data, we look forward to evaluating CoVepiT’s efficacy in a Phase 1 clinical study expected to be initiated by the end of 2020/early 2021.”
OSE is currently in Phase 3 trials validating that its own Memopi epitope (neo-epitope) optimization technology can successfully induce a T-cell response that offers long-term protective immunity in the oncology space. The methodology employs “sentinel” cells present in barrier tissues such as the respiratory tract and the lungs. This barrier tissue effectively serves as the interface between the external world and the body. When the sentinels, or memory leukocytes, encounter danger at the barrier, they migrate into the cell to initiate the immune response. What makes the OSE approach function is the activation of those cells that “remember” the peptides of the virus as it approaches, which can then eliminate infected cells before significant virus replication. Because of the nature of its attack on the body, this same technology can be applied to fight SARS-CoV-2.
“The CoVepiT program is based on a clinically validated technology now shown to induce tissue-resident memory T lymphocytes (Trm) sentinel response against multiple parts of SARS-CoV-2, suggesting it provides a long-term protective immunity, as opposed to transient protection provided by neutralizing antibodies,” explained Nicolas Poirier, chief scientific officer of OSE. “In addition, this vaccine is designed to anticipate ongoing recurrent virus mutation and evolution, further adding to its long-term protective potential.”
In seeking to take the successful oncology approach into the realm of COVID-19, OSE studied the immune systems of patients who had recovered from the virus—those with moderate, severe or asymptomatic presentations of COVID-19, as well as MERS, a previous coronavirus. They were able to identify the path of the virus as well as a small peptide of the virus that was recognized by the lymphocytes of the convalescing survivors.
After mapping this hallmark of the immune system of cured patients, the team analyzed 46,000 different sequences of the virus from all over the world. In preparing their trial vaccine, they were careful to screen out the mutations found in small, regional hotspots to drive a broadly effective response. However, the methodology does allow for further mutation of the virus. Scientists have watched the coronavirus evolve for 15 years, and logically believe that it will continue to do so while conserving existing peptides as well, making CoVepiT nimble enough to attack future iterations.
“We’ve shown that we can quickly modify the technology [from cancers] to COVID. Tomorrow, we can change a peptide using the same technology and drawing on what was learned from healed COVID and MERS patients,” asserts Poirier.
The first generation of COVID-19 vaccine trials may have lacked effectiveness because of the virus’s ability to escape the weapon and mutate, a feature of many cancerous tumors as well. In the advanced trials for the non-small cell lung cancer vaccine, the researchers are aiming at five different targets within the tumor. In the COVID trials, they are targeting 11, so if the virus mutates in one target, there remain 10 more potential successes. This multi-target approach promises high potential on its own, or in conjunction with the many antibody approaches currently in development.
“We are building a second-generation vaccine built for the long term, using learning from the first generation. We do not target antibody response, we target a 2-lymphocyte response,” Poirier concludes. “Our approach may also complement an antibody approach—perhaps with a first vaccine for antibodies and a second 2-lymphocyte vaccine for longer-term immunity.”