Rotavirus infections are the most common and important cause of severe dehydrating diarrhoea in young children of developing countries. Development of new vaccines is an ongoing issue to effectively prevent and tackle emergence of these infections. A European consortium approached rotavirus vaccination from a different perspective. The project ‘Herpesvirus-based vaccines against rotavirus infections’ (HEVAR) aimed to develop and evaluate innovative genetic anti-rotavirus vaccines based on HSV-1 vectors. To achieve that, project partners tested a large collection of HSV-1–based and DNA-based vectors expressing mouse, monkey and human rotavirus antigens. HEVAR was a collaborative effort between four European and four South American groups. European partners ensured transfer of knowledge and technology regarding HSV-1–based gene transfer vectors to South America. A local platform for HSV-1 vector production in South America was set up accompanied by appropriate personnel training. Reciprocally, European teams learned about the biology of rotavirus and other endemic viruses with high social cost in South America. Experimentally, consortium members cloned the genes encoding the four structural proteins (VP2, VP4, VP6 and VP7) and one non-structural protein (NSP4) from 4 different rotavirus strains in HSV-1–based vectors. The expression profiles of these vectors and the properties of the expressed rotavirus proteins were characterised in infected cells. Subsequent evaluation of the vectors in animal models revealed that they could elicit significant antibody and cellular-specific responses. A series of experiments were conducted to compare the relative efficacy of different routes of immunisation, and to characterise the nature of the humoral responses. Some of the raised antibodies displayed neutralising activity and also a significant level of protection was observed against challenge with live virus, especially when expressing combinations of rotavirus proteins. HEVAR project results clearly demonstrated the feasibility of HSV-1–based vector vaccines to immunise against rotaviruses. It remains to be determined how this immunisation approach compares to existing vaccines.
Discover other articles in the same domain of application
Largest-ever IMI Immunology Project 3TR: Accelerating Precision Medicine for Immune-Mediated Diseases
31 October 2019