Developing translational research capacity: development of vaccines from concept to preclinical assessment (ConVAC)
The benefits of vaccination are undeniable at both individual and social level. As a major strategic direction in public health, vaccination takes these benefits far beyond individual protection against many infectious diseases, by eliminating / eradicating / reducing morbidity and complications associated with infectious diseases.
However, even if the benefits of vaccination are obvious, in a modern society where unfiltered information leads to a decline in trusting a vaccine, scientific arguments must be continuously updated to demonstrate their efficacy, safety and significant improvements. Additionally, the current trend to use a limited number of previously tested antigens available on the market can lead to maintaining a limited vaccine pressure on a subpopulation of microorganisms, which can lead to antigenic drift of circulating microorganisms and consequently reduced vaccine protection. As a result, the continuous development of new antigens is necessary, as well as the presence of adequate adjuvants for the low antigenicity of some microbial components in current vaccine formulations available on the market.
This consortium provides the necessary framework for vaccine development through studies involving better antigen characterization, optimization of its formulation, extension of immunogenicity characterization, protection assessment and, finally, documentation of non-clinical trials according to pharmaceutical regulations, with the main purpose of increasing and consolidating scientific performance in the field of vaccinology.
In addition, the objectives of the consortium will include the development and consolidation of laboratory-based animal studies completed with an accredited research and development service and the acquisition of new scientific skills in the field of vaccinology, through training and specialization of young researchers.
This consortium provides the necessary framework for the development of a vaccine through:
studies that will ensure the development of the antigen;
studies on the optimization of the formulation of this antigen;
developing new ways to characterize antigen-adjuvant complexes;
evaluating the protection given by antigen-adjuvant complexes;
assembling the documentation of non-clinical studies according to pharmaceutical regulations.
Some of the expected results of this project are:
new ways of producing, formulating and administering antigens with vaccine potential;
a common methodology for exploring and characterizing the structure and immunogenicity of vaccine candidate proteins;
testing methodologies including the development of new in vitro evaluation systems;
animal studies completed with an accredited research and development service;
scientific skills in the field of vaccinology through specialized training of young researchers.
Project 1 - Rational models for the selection of vaccine antigens and their structural evaluation:
The project systematizes the available information about the antigenic structure of proteins that are vaccine candidates and evaluates methods of production based on classical methods or genetic engineering methods. The methodology will be developed for the general framework but the verification will be done starting from the preliminary results obtained in the joint projects. The goal is to obtain and characterize a candidate / multiple antigen candidates and / or an adjuvant candidate.
Project 2 - In vitro experimental studies and evaluation of the structure - efficiency relationship in vaccine development:
The project aims to perform in vitro testing of antigens / adjuvants in cellular models, to monitor the differentiation of dendritic cells, to evaluate the immunomodulatory / adjuvant properties of vaccine components, along with those of the adjuvant. Although the project will include possible animal models, it will mostly focus on in vitro evaluation methods.
Project 3 - Development of in vivo study capacity to evaluate vaccine efficacy:
The project aims to further develop a methodology for in vivo testing (i.e. in animal models) of vaccines / vaccine-adjuvant complexes in order to obtain information about the potential efficacy of a vaccine.
Project 4 - Development of the preclinical methodology for a new vaccine / adjuvant:
The project aims to develop the methodology of pharmaceutical testing of the vaccine, to validate it in vivo models and to prepare the documentation required for the accreditation of the testing unit.
Fig. 1. Cryo-electron micrograph showing glycoprotein-coated viral particles.
Coordinator: "Cantacuzino" National Institute of Medical-Military Research and Development Bucharest
Partners: Institute of Biochemistry of the Romanian Academy (IBAR), "Ion Ionescu de la Brad" University of Agricultural Sciences and Veterinary Medicine Iasi, "Victor Babeș" National Research and Development Institute in Pathology and Biomedical Sciences (INCDVB) Bucharest
Project funded by the Ministry of Research and Innovation, CCCDI - UEFISCDI, project number PN-III-P1-1.2-PCCDI-2017-0529 / 62PCCDI / 2018, from PNCDI III.