Horizons research projects

Study details 

Gonorrhoea is the second most common sexually transmitted infection worldwide, with disproportionately high rates in Māori, Pacific Peoples and young adults in Aotearoa New Zealand. Up to half of infections in females are asymptomatic, increasing the risk of untreated disease, infertility and ongoing transmission.  

Current diagnosis relies on laboratory-based nucleic acid amplification tests (NAATs), which can take up to a week, delaying treatment and creating barriers to care. Additionally, rising antibiotic resistance in Neisseria gonorrhoeae (gonococcus) further highlights the need for rapid and accurate diagnostics. 

We propose developing a rapid point-of-care lateral flow assay targeting lipid oligosaccharide (LOS), a conserved and highly expressed gonococcal surface antigen involved in virulence. Our approach uses nanobodies (single-domain antibodies derived from camelids), which are highly stable, specific and well suited for portable diagnostics. We have already identified LOS-binding nanobodies and will optimise these for a low-cost assay capable of detecting both symptomatic and asymptomatic gonorrhoea infections quickly, in low resource settings.  

A nanobody-based detection scheme can be translated to different pathogens if the nanobody sequence is changed. The methodology established here, and in a related project developing carbon-based nanobody diagnostics for Norovirus, can be applied to develop nanobodies against any conserved antigen, enabling broad diagnostic development for infectious organisms. We will disseminate not only the results of our project but also the capability in developing this technology. 

Research Design and Methodology 

This project builds on a 6-month Te Niwha funded project. Using both synthetic nanobody libraries and llama immunisation approaches, we identified nanobodies that recognise conserved regions of gonococcal LOS. Synthetic libraries were screened using phage display against the conserved 2C7 LOS epitope, leading to the identification and affinity maturation of lead nanobody candidates. To improve recognition of native LOS, additional screening rounds alternating between purified LOS and the 2C7 peptide identified four lead nanobodies with cross-reactivity to both targets. However, further characterisation revealed weak binding to purified gonococcal LOS.  In parallel, a biological nanobody library was generated through llama immunisation and phage display in collaboration with the University of Zurich, which identified an additional four nanobody binders from diverse antibody gene families. Here we will characterise lead nanobodies from the llama immunisation for stability, specificity, and diagnostic suitability. \

Nanobodies will be expressed in Escherichia coli and purified using our existing protocols. Binding affinities to both 2C7 and LOS will be tested via established ELISAs and confirmed in higher resolution by z or isothermal titration calorimetry. Nanobodies will also be tested for stability and binding under various physiological conditions including temperature, pH, and salt to determine limitations for use in a lateral flow test.

Binding to clinical N. gonorrhoeae isolates (in collaboration of AI Broomhead) will be assessed using ELISAs, flow cytometry and confocal microscopy. Specificity testing will include screening against commensal Neisseria species to assess cross-reactivity.  

Contingency plan: Although unlikely given pre-screening conducted in Zurich obtained binders, if none of the lead nanobodies bind LOS/2C7 with high affinity we will go back to the original immune library (from the llama immunisation) and use phage display to screen for LOS binders. 

We will characterise the three-dimensional structure of our lead nanobody(s) bound to LOS and/or 2C7 to inform binding improvements and molecular modelling. With collaborators at Cardiff University (Prof Dafydd Jones), we will perform molecular dynamics simulations to determine sites for conjugation of the nanobody to planar surfaces to obtain information about the most optimal conjugation orientations for preserving detection sensitivity. These interdisciplinary approaches will ensure the limits of detection are as a low as possible for future devices.  

At the end of the one-year project we anticipate having a conjugation ready nanobody that can be used for prototype testing with clinical samples. 

Most antibiotics are prescribed in primary care settings such as GP clinics, making it a critical environment for tackling the serious issue of antimicrobial resistance. A new research project will build on work funded by Te Niwha, which developed Te Whata Kura national antibiotic guidelines that are now being used around the country in both hospital and community settings. 

Study details

In Aotearoa New Zealand there are large inequities in infectious disease incidence and outcomes. Increasing antimicrobial resistance (AMR) magnifies the risk of infectious disease, threatening successful treatment and prevention  

With 95% of antibiotic prescribing occurring in primary care, appropriate antibiotic prescribing is a critical intervention point to address health inequities and support antimicrobial stewardship (AMS). However, prescribers currently lack practical, equity-centred approaches to monitor and support consistent, appropriate prescribing. 

In 2025, a Te Niwha-funded project resulted in the development of Te Whata Kura national antibiotic guidelines. The availability of national guidelines on a single platform provides a consistent benchmark to support appropriate antibiotic prescribing, AMS and equity. 

This Horizon project aims to build on previous research and advance AMS and equity through innovations to support consistent and appropriate antibiotic prescribing and primary care. 

One innovation is a framework to embed cultural safety in antibiotic and other clinical guidelines. Uptake and usage of Te Whata Kura guidelines have exceeded expectations. However, while antibiotic guidelines provide evidence-based recommendations, they do not guarantee best practice prescribing and equity. 

Cultural safety provides a framework to support critical reflection on clinical guideline development processes, content, and use to support excellent care and health equity. Previous qualitative research exploring whānau Māori perspectives on antibiotic guidelines use identified an expectation for culturally safe guidelines that are responsive to people and context.  

The second innovation is an evidence-and user-informed data sharing approach that utilises storytelling. Research has shown that sharing quantitative data alone with prescribers seldom results in sustainable behaviour change. Storytelling is an emergent approach that seeks to contextualise and communicate data effectively through the inclusion of narrative or stories. The concept is broad and ranges from comparative data sharing accompanies by messaging promoting behaviour change, to using narrative and patient stories to make data feedback even more memorable, engaging and emotionally resonant. 

Primary care and prescriber insights will inform development of an antibiotic prescribing data sharing prototype that meets their needs, integrates storytelling, and is compatible with primary care data structures.