Generation and characterisation of vaccines against WHO R&D Blueprint priority viruses using a Sendai Virus vaccine vector platform.

Nipah virus (NiV), Rift Valley fever virus (RVFV), and Crimean-Congo haemorrhagic fever virus (CCHFV) are zoonotic viruses considered by the WHO to be top priority public health risks for which safe and effective vaccines are urgently needed. These viruses infect a range of different species, including livestock and humans, causing substantial health and economic consequences. We developed reverse genetics technology for a paramyxovirus that facilitates its use as a vector for vaccine antigens. This paramyxovirus can infect many different cell types from different species, including mucosal epithelium, making it highly suitable for use as a vaccine vector. This project will exploit our paramyxovirus reverse genetics technology to generate and characterise novel vaccines against these top public health priority viruses. The project will provide an excellent opportunity for training in molecular virology and paramyxovirus reverse genetics, vaccine antigen design, vaccine characterisation in vitro, and design and execution of vaccine immunogenicity studies in appropriate animal models. This will include excellent training in B and T cell immunology to study immune responses to vaccine antigens. It would be suitable for individuals with research experience in virology, molecular biology, immunology and/or vaccinology, with degrees (BSc/MSc) in a relevant biological sciences degree, medicine or veterinary medicine.

Nipah virus (NiV), Rift Valley fever virus (RVFV), and Crimean-Congo haemorrhagic fever virus (CCHFV) are zoonotic viruses considered top priority public health risks by the WHO for which safe and effective vaccines are urgently needed.

NiV in found south and south-east Asia. It infects humans and pigs, causing devastating respiratory and encephalitic diseases in humans. Fruit bats are a common reservoir and NiV is often transmitted to humans and pigs through fruit bat droppings. Vaccines for humans and pigs will be important in controlling NiV.

RVFV in found in sub-Saharan Africa and the Arabian Peninsula. It is transmitted primarily through mosquitoes, with livestock being a major reservoir. Diseases range from mild flu-like syndromes to severe haemorrhagic fever and encephalitis. Vaccines have been developed for livestock, albeit with side effects, such as abortions in pregnant livestock. Therefore, effective and safe vaccines for both livestock and humans are needed.

CCHFV is found in Africa, Middle East, Asia and some European countries. It infects humans, livestock, wild mammals and birds. It is primarily a tick-borne virus, but transmission may also result from direct contact with infected blood and tissues from humans or livestock. Symptoms range from mild flu-like symptoms to sever haemorrhagic fever and multi-organ failure. There are no vaccines against CCHFV.

Because of their current impact and potential for devasting expansion to other populations around the world, NiV, RVFV and CCHFV are considered by the WHO to be top priority public health risks for which safe and effective vaccines are needed. To address this, our project will exploit our reverse genetics technology for a paramyxovirus to generate novel vaccine candidates against these devastating viruses. This paramyxovirus can infect different cell types from different species, including mucosal epithelial cells. Importantly, it is not known to cause disease in livestock or humans, making it suitable for use in both. Its cell tropisms make it suitable for parenteral or mucosal delivery.

We previously used this paramyxovirus to generate vaccine candidates against human and bovine respiratory viruses, which induced strong antibody responses in mice. This provided proof-of-principle demonstrating the potential to exploit this virus as a vaccine vector. In preliminary studies, we have generated vaccines against NiV using this paramyxovirus, which efficiently expresses NiV vaccine antigens in vitro. This project will extend the NiV work to RVFV and CCHFV antigens, which will be inserted into our paramyovirus vector using our reverse genetics technology. The resultant viruses will be characterised in vitro to confirm expression of the appropriate vaccine antigens and in vivo to determine their ability to induce protective immune responses in appropriate animal models.

The project will provide an excellent training in molecular virology, paramyxovirus reverse genetics, vaccine antigen design, vaccine characterisation, and design and execution of vaccine studies in appropriate animal models. This will include excellent training in B and T cell immunology to study adaptive immune responses. It would be suitable for individuals with research experience in virology, molecular biology, immunology and/or vaccinology, with degrees (BSc/MSc) in a relevant  biological sciences degree, medicine or veterinary medicine.