Search

Nipah virus is an emerging zoonotic pathogen that causes disease outbreaks in South-East Asia with high case fatality rates. It is considered to be a public health risk and there are limited medical countermeasures for treatment or prevention, and as a Biosafety Level 4 pathogen, limited places able to work with Nipah virus. Animal models are required for the evaluation of medical countermeasures. Female hamsters, in groups of three or six were infected IP with a sixlog10 range doses of Nipah virus Malaysia. Hamsters were weighed daily and checked every four hours. Animals were scored on the condition of coat, posture, eyes, respiration, activity and neurological signs. Hamsters were monitored for 14 post-infection. Organ samples were taken for histopathological analysis and for viral load determination. Immunohistochemistry was performed with anti-Nipah virus glycoprotein antibody. Hamsters were susceptible to infection with NiV-M by the IP. route at all challenge doses. Animals started showing signs of infection and succumbing to disease in a dose-dependent manner, succumbing between days 4 and 9. The progression of clinical signs was rapid. Viable virus could not be detected in any of the organs, or in the blood of any of the eight animals that survived the infection. No viable virus was recovered from six of the animals that succumbed to infection. Where viable virus was recovered, it was predominantly in the spleen, brain or lung. No pathological changes were observed in the brain whislt many pathological changes were observed in the lungs. Immunohistochemistry showed NiV was localised to the lung blood vessel endothelial cells in animals that succumbed. We demonstrated that, similar to previously known data, the hamster is susceptible to Nipah virus. We have shown that disease progressed rapidly, and that the lungs were the main site for viral replication and pathological changes. © Crown copyright (2022), Dstl. [ABSTRACT FROM AUTHOR]

• A novel dual route vaccination using the MERS-CoV RBD sub-unit has been developed. • Murine antisera induced to the RBD protein , were neutralising in vitro. • MERS-CoV susceptibility was induced in naïve mice with Ad5hDPP4. • Passive transfer of anti-RBD sera protected susceptible mice. • Protected mice had a significantly reduced viral titre (P = 0.02) in their lungs. Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. The murine antisera induced were fully-neutralising in vitro for two separate clinical strains of the MERS coronavirus (MERS-CoV). To test the neutralising capacity of these antisera in vivo , susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. Subsequent challenge of the recipient transduced mice by the intra-nasal route with a clinical isolate of the MERS-CoV resulted in a significantly reduced viral load in their lungs, compared with transduced mice receiving a negative control antibody. The murine antisera used were derived from mice which had been primed sub-cutaneously with a recombinant fusion of RBD with a human IgG Fc tag (RBD-Fc), adsorbed to calcium phosphate microcrystals and then boosted by the oral route with the same fusion protein in reverse micelles. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV. [ABSTRACT FROM AUTHOR]