Defining the role of cross-protective antibodies in protection against emerging viruses at the species and sub-species level

RNA viruses, such as paramyxoviruses and coronaviruses, continually evolve in response to external stimuli such as antibody selection pressure. This evolution is aided by the high error rates of the viral RNA polymerases of these viruses. Error prone replication, rapid replication and large epidemics/pandemics also contribute to the general accumulation of many synonymous nucleotide changes in the genome and non-synonymous protein changes with neutral effects on phenotype. Discriminating between phenotypically relevant amino acid changes and those that are non-functional is vital, especially in identifying mutations that could confer infection in new hosts, and for the design and application of vaccines. Within this project we will examine how variation in the viral glycoproteins (vGP) of two important groups of viruses, beta-coronaviruses and Henipaviruses affects their neutralisation by established and/or experimental vaccines. Focusing on the ongoing SARS-CoV-2 pandemic we will investigate whether existing vaccines can provide robust immunity to emerging/established variants. On a broader scale, we will examine the breadth of immunity offered by Henipavirus-based vaccines and whether neutralising antibody responses to these vaccines are capable of neutralising different species within the same genera. Building on these results we will characterise the epitopes involved to define the molecular mechanisms underpinning this neutralisation, building a detailed understanding of intra-species and inter-species protection. These data will inform vaccine design to protect livestock from future known or unknown Henipavirus outbreaks and to prevent onward transmission to humans. BBSRC priority areas: This research will address the BBSRC priority areas of animal health, collaborative research and research that informs public policy. As part of the Genotype to Phenotype UK (G2P-UK) Consortium, we will investigate the ability of SARS-CoV-2 variants and related beta-coronaviruses to infect mammalian hosts that could act as reservoirs for sustained SARS-CoV-2 transmission in human and animal populations. We will also assess the effectiveness of SARS-CoV-2 vaccines against emerging or established variants in collaboration with G2P-UK and Public Health England (PHE), with the aim of informing public health strategies. In addition, Henipaviruses have been shown to cross the species barrier and cause pathology in humans and animals, both naturally and experimentally. In particular, Nipah virus, has been identified by the World Health Organisation as a priority zoonotic pathogen that requires research and development. We therefore propose to develop a cross-protective vaccine that could prevent future outbreaks and sustained transmission of Henipaviruses (known or unknown) that pose a major threat to agriculture, livestock and public health.