HEVAR will develop herpes simplex virus type 1 (HSV-1)-based vectors for the generation and analysis of rotavirus-specific expression and display model vaccines.
Our approach is based on the possibility of engineering HSV-1-based vectors expressing and/or displaying rotavirus antigens, either individually or in combination, alone or together with immune-modulator genes.
Our goal is to evaluate the ability of these vectors to elicit protective immune responses against rotavirus infection in normal and transgenic mice, therefore helping to elucidate the contribution of individual rotavirus antigens, and of different components of the immune system, to the architecture of the immune response and to protection upon rotavirus challenge in this animal model.

HEVAR is a collaborative project involving four academic laboratories from four European countries (France, Switzerland, Germany, Italy) and four academic laboratories belonging to three South American countries (Argentine, Brazil, Uruguay). The overall scientific goal of HEVAR is to contribute to a better understanding of the immune biology of rotavirus infections using a novel generation of gene transfer vectors derived from herpes virus simplex type 1 (HSV-1), as a first step towards the development of innovative genetic vaccines to fight against these pathogens, which are the most common and important cause of severe dehydrating diarrhoea in young children of developing countries.

In addition to contributing to a better understanding of the immune biology of rotavirus infection and of evaluating the feasibility of using HSV-1 vectors as anti-rotavirus vaccines, the main deliverables of HEVAR will be a set of toolboxes containing a large collection of HSV-1-based and DNA-based vectors expressing human and mouse rotavirus antigens that will be evaluated in mice, which will be rendered accessible to any academic team wishing to use them for vaccine development or fundamental research on rotaviruses.

A last set of deliverables will consist in a series of scientific meetings and events required to achieve the transfer of knowledge and complex technology required to generate, produce, and evaluate, the HSV-1-based gene transfer vectors in South America, therefore, improving the human capital and the technological competence of these countries, as well as the reciprocal transfer to European teams of knowledge on the biology of rotavirus and other endemic viruses with high social cost in South America, as a way to strengthen the awareness to, and the understanding of, these neglected diseases.

Diarrhoea caused approximately 2 million deaths per year worldwide in the last decade and was responsible for an estimated 20% of mortality in children aged less than 4 years in developing countries. Rotaviruses are the most common cause of severe dehydrating diarrhoea in young children in these countries, accounting for 20% to 60% of hospitalized cases. Rotavirus infection and disease cannot be controlled by hygiene and sanitation measures and almost all children will be infected with rotavirus in the first years of life. An estimated 140 million diarrhoeal episodes, and a minimum of 450,000-600,000 deaths per year, with immense medical/societal costs, mainly in developing countries, highlights the urgent need for the development and deployment of an effective prophylactic anti-rotavirus vaccine, that would have universal application as part of childhood immunization programs.
The overall scientific goal of HEVAR is to contribute to a better understanding of the immune biology of rotavirus infections using a novel generation of gene transfer vectors, as a first step towards the development of innovative genetic vaccines to fight against these pathogens. To this end, HEVAR will develop herpes simplex virus type 1 (HSV-1)-based vectors for the generation and analysis of rotavirus-specific expression and display model vaccines. Our approach is based on the possibility of engineering HSV-1-based vectors expressing and/or displaying rotavirus antigens, either individually or in combination, alone or together with immune-modulator genes. Our goal is to evaluate the ability of these vectors to elicit protective immune responses against rotavirus infection in normal and transgenic mice, therefore helping to elucidate the contribution of individual rotavirus antigens, and of different components of the immune system, to the architecture of the immune response and to protection upon rotavirus challenge in this animal model. This project entails therefore a truly innovative procedure that will generate knowledge and technologies relevant for the ultimate development of a novel generation of prophylactic vector vaccines, rationally designed to prevent human rotavirus infections.
At the biotechnological level, the main deliverables of HEVAR will be a set of toolboxes containing a large collection of HSV-1-based and DNA-based vectors expressing mouse rotavirus antigens that will be already evaluated in mice, as above described. These toolboxes will also contain a set of vectors expressing human rotavirus antigens from strains with epidemiological significance in South America. All these tools will be rendered accessible to any academic team wishing to use them for vaccine development or fundamental research on rotaviruses.
A last set of deliverables will consist in transfer of knowledge and technology. This includes, on one hand, the transfer from European groups to South American partners, of the knowledge and complex technologies required to locally generate, produce, and evaluate, the HSV-1-based gene transfer vectors, therefore, improving the human capital and the technological competence of these countries. On the other hand, the South American partners will transmit to European teams their knowledge on the biology of rotavirus and other endemic viruses with high social cost in South America, therefore strengthening the awareness to, and the understanding of, these neglected diseases.