The DECODE project
Duration of the project
"Pius Brânzeu" Emergency Clinical County Hospital Timisoara, Center for
Gene and Cellular Therapies in Cancer - OncoGen
"Cantacuzino" National Medical-Military Research-Development Institute
Development of a prophylactic peptide vaccine for COVID-19 based on epitopes recognized by the immune system (DECODE)
The specific objectives
- The development of a candidate vaccine with proven efficiency against SARS-CoV-2 in advanced preclinical studies and of potential adjuvants able to potentiate the action of the vaccine and the immunization process, without inducing adverse effects;
- Development of studies in vivo, on animal models, in order to elucidate the etiopathogenic mechanisms of the SARS-CoV-2 virus and to combat them with the help of potential vaccines;
- Elaboration of the necessary documentation for phase I/II clinical studies in order to test potential vaccines.
The novelty of this project lies in the fact that the vaccine is based on the use of immunogenic synthetic long peptides (synthetic long peptides - SLP), obtained from the S protein structure of the SARS-CoV-2 virus, which specifically activate T helper lymphocytes, cytotoxic T lymphocytes and B lymphocytes, in a manner dependent on the population phenotype (major histocompatibility system molecules – MHC class I and class II).
The OncoGen Centre was included on April 4, 2020, in the list of institutions developing a vaccine against SARS-CoV-2, by the World Health Organization (WHO).
Fig. 1. Mode of action on the immune system level of the proposed vaccine
The most optimistic projections for controlling the COVID-19 pandemic include a combination of measures that have proven effective in the past: social transmission control measures, new antiviral drugs to treat symptoms, and the development of a vaccine to prevent infection in people at risk or the development of severe forms of the disease. Antiviral drugs will limit the burden on the health system, and population screening will allow individuals who show immunity to be kept active, but disease transmission will only be stopped by the development and administration of a vaccine.
It is not yet known whether a vaccine against SARS-CoV-2 will confer long-term or short-term immunity because much remains to be deciphered related to the pathogenesis of this viral infection and the immune system's reaction to the virus. Unlike influenza viruses, the coronavirus does not accumulate mutations as frequently and has only one key point of interaction with host cells, the S protein, which is the target of most proposed vaccine strategies. Therefore, there is reason to believe that a vaccine could act effectively and usefully. The coronavirus pandemic has caused global economic destabilization and a recession comparable to the Great Depression of the 1930s, from which we can only begin to recover once we ensure the immunity of the population that can thus be reintegrated into active economic life. Immunity can only be ensured by effectively vaccinating the entire population that has not been infected. Alternatively, the virus will become seasonally endemic over time, causing disease, sometimes fatal, until the natural immunity of the population is acquired, which will thus be periodically incapacitated. Even if, at the earliest, an anti-SARS-CoV-2 vaccine will be available in 18 months, it is necessary to completely remove the gloomy specter that this epidemic generates on the health system and the conduct of normal social and economic activities.
The closest we can expect a vaccine to be available is no earlier than 18 months because protocols must be followed to ensure the effectiveness and safety of a potential therapy in humans. First, a part of the virus must be chosen to be recognized by the immune system and initiate a protective reaction; this viral protein must also not differ between circulating variants of the virus and confer protection for all and most of the population. Once this immunogen is selected, it must be tested on isolated human cells and laboratory animals to demonstrate that it is non-toxic and has a positive immune-stimulating effect.
Most of the vaccination strategies against SARS-CoV-2 infection that are currently in development use pre-existing platforms such as non-replicating viral vectors, DNA, RNA, inactivated virus or protein subunits. The vaccine proposed by the "Pius Brânzeu" Timișoara County Emergency Clinic Hospital (OncoGen Center) in partnership with the "Cantacuzino" National Institute of Medical-Military Research uses synthetic long peptides (SLPs), a vaccination strategy derived from oncology therapy, which will stimulate the appearance of an immune response by T lymphocytes, especially cytotoxic T lymphocytes, capable of destroying virally infected cells. Long synthetic vaccine peptides are fragments of the S (spike) protein of SARS-CoV-2, selected specifically for the immunophenotype of the Romanian population. Second, our long synthetic peptide strategy stimulates humoral immunity and the emergence of protective antibodies against SARS-CoV-2.
The partnership between the OncoGen Center within the Emergency County Clinical Hospital "Pius Brânzeu" Timișoara and the National Institute of Medical-Military Research "Cantacuzino" resulted in the winning of this research project through a national competition within the SOLUTIONS 2020 program, a competition in which we participated for to obtain the funding necessary to carry out the in vitro studies (on cells) and in vivo (on an animal model) necessary for the development of a vaccine against SARS-CoV-2 applicable to humans, in the desire to stop, through modern vaccinology methods, the current pandemic.
Fig. 2. Graphical map of the synthetic long peptides (SLPs) components of the SARS-CoV-2 vaccine