DECODE Project

Development of a prophylactic peptide vaccine for COVID-19 based on immune recognized epitopes (DECODE)

PROJECT DETAILS (PDF)

Funding contract No 11Sol/2020

Timeframe: 2020-2021

Funding: 3.500.000 RON (State Budget through the Executive Unit for Financing Higher Education, Research, Development and Innovation)

Programme: Increasing the competitiveness of the Romanian economy through research, development and innovation (PNCDI III) – Solutions 2020 – 1 – Development of new technologies, drugs and vaccines for the prevention of SARS-CoV-2.

Coordinator: OncoGen Centre, “Pius Brânzeu” Emergency Clinical County Hospital Timișoara

Partner: “Cantacuzino” National Institute for Medical and Military Research and Development

Specific objectives:

(1) Develop a candidate vaccine with proven efficacy against SARS-CoV-2 in advanced preclinical studies and potential adjuvants able to potentiate the action of the vaccine and the immunization process without inducing adverse effects;

(2) Development of in vivo studies in animal models to elucidate the aetiopathogenic mechanisms of SARS-CoV-2 and to combat them with potential vaccines;

(3) Development of documentation for Phase I/II clinical trials to test potential vaccines.

The novelty of this project is that the vaccine is based on the use of synthetic long peptides (SLPs), derived from the SARS-CoV-2 S protein structure, which specifically activate T helper, T cytotoxic and B lymphocytes in a population phenotype-dependent manner (major histocompatibility system molecules – MHC class I and class II).

The OncoGen Centre has been 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 of the proposed vaccine on the immune system

The most optimistic projections for controlling the COVID-19 pandemic include a combination of measures that have proven effective in the past: social measures to control transmission, new antiviral drugs to treat symptoms, and the development of a vaccine to prevent people at risk from becoming infected or developing severe forms of the disease. Antiviral drugs will limit the burden on the health system, and population screening will keep individuals with immunity alive, but disease transmission will be stopped only by the development and administration of a vaccine.

It is not yet known whether a vaccine against SARS-CoV-2 will confer immunity in the long or short term because much remains to be deciphered about the pathogenesis of this viral infection and the immune system’s response 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 destabilisation and a recession comparable to the Great Depression of the 1930s, from which we can only begin to recover once the population is immune and can be reintegrated into active economic life. Immunity can only be ensured by effective vaccination of the entire population that has not been infected. Alternatively, the virus will over time become endemic, seasonal, causing disease, sometimes lethal, until the natural immunity of the population is acquired and the population is periodically incapacitated. Even if, at the earliest, an anti-SARS-CoV-2 vaccine will be available in 18 months’ time, it is necessary for the complete removal of the grim spectre that this epidemic is generating on the health system and the conduct of normal social and economic activities.

The earliest we can expect a vaccine to be available is no earlier than 18 months because protocols must be followed to ensure the efficacy and safety of a potential human therapy. First, a part of the virus must be chosen that is recognised by the immune system and initiates a protective response; this viral protein must also not differ between circulating variants of the virus and confer protection for all and the majority 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-boosting effect.

Most of the vaccination strategies against SARS-CoV-2 infection that are currently in development use pre-existing platforms such as non-replicative viral vectors, DNA, RNA, inactivated virus or protein subunits. The vaccine proposed by the “Pius Brânzeu” Timisoara Emergency Clinical Hospital (OncoGen Centre) in partnership with the “Cantacuzino” National Institute for Medical and Military Research uses long synthetic peptides (SLPs), a vaccination strategy derived from cancer therapy, which will stimulate an immune response by T lymphocytes, especially cytotoxic T lymphocytes, capable of destroying virally infected cells. The synthetic long vaccine peptides are fragments of the SARS-CoV-2 S protein (spike), selected specifically for the immunophenotype of the Romanian population. Secondarily, our long synthetic peptide strategy stimulates humoral immunity and the emergence of protective antibodies against SARS-CoV-2.

The partnership between the OncoGen Centre of the “Pius Brânzeu” Emergency County Clinical Hospital in Timișoara and the “Cantacuzino” National Institute for Medical and Military Research resulted in the winning of this research project through a national competition within the SOLUTIONS 2020 programme, a competition in which we participated to obtain the necessary funding to carry out in vitro (on cells) and in vivo (on animal models) studies needed to develop a vaccine against SARS-CoV-2 with human applicability, in the desire to stop the current pandemic using modern vaccinology methods.

Fig. 2. Graphic map of long synthetic peptides (SLPs) components of the SARS-CoV-2 vaccine