Emerging viruses often pose a threat to human populations due to the lack of pre-existing immunity. The WHO has prioritised groups of viruses for vaccine research and development, particularly viruses with pandemic potential. We have been investigating the effectiveness of vaccines against two of these priority groups of viruses, betacoronaviruses and henipaviruses, at an intraspecies and genus-wide level. In this study, the effectiveness of COVID-19 vaccines were examined in an older adult cohort to understand the antigenicity of SARS-CoV-2 variants. This analysis was further expanded to understand whether pre-existing immunity against SARS-CoV-2 can provide cross-protection against other betacoronaviruses, particularly sarbecoviruses, which are phylogenetically similar to SARS-CoV-2. For the henipaviruses, bio-banked sera from a pig immunisation study were analysed, whereby animals received homologous prime-boosts of Nipah virus and Hendra virus-based vaccines. Cross-reactive antibodies were detected against all the henipaviruses tested, but cross-neutralising antibodies only against Nipah and Hendra virus. Immunisation of mice with Nipah virus and the more distantly related Ghanaian bat henipavirus immunogens showed a degree of cross-neutralisation using homologous and heterologous vaccination regimes, but did not confer protection in a hamster challenge model. However, hamsters did exhibit evidence of reduced pathology and virus infiltrates in tissue sections of the brain, lungs and spleen with homologous prime-boost vaccination with a Ghanaian bat henipavirus subunit vaccine. This data suggests that pre-existing immunity against one virus may provide cross-protection against related viruses, but the utility of these vaccines may become limited with more distantly related viruses. This highlights the requirement for broad and novel vaccine development strategies against emerging viruses in any outbreak scenario.