Researchers developing a controlled human infection model (CHIM) for oropharyngeal gonorrhea used a predefined genomics-plus-clinical workflow to reduce a pool of 5,881 Neisseria gonorrhoeae isolates to 86 eligible candidates, then selected five strains to advance to phenotypic testing. Most exclusions reflected clinically significant antimicrobial resistance or limited contemporary global relevance, aligning selection with safety and vaccine-evaluation goals.
To begin, the team specified eight criteria integrating clinical history, phenotypes, and whole-genome data to ensure that candidate strains were globally relevant, suitable for assessing current and future vaccines, and unlikely to cause disseminated disease or carry clinically significant resistance. They applied this framework to adult clinical isolates collected in Victoria, Australia from Jan 1 to Dec 31, 2017 and from July 1, 2019 to June 30, 2021. This step screened out 5,795 of 5,881 isolates, leaving 86 strains spanning five multilocus sequence types and six multiantigen sequence types, many represented by single isolates.
Next, investigators prioritized breadth and representation. From the 86 candidates, they chose five isolates that covered phylogenetically distinct groups and included strains obtained from different anatomic sites. These five will undergo detailed phenotypic characterization before a single challenge strain is finalized for the CHIM.
Contagion spoke with study investigator Eloise Williams, MBBS, BMedSci, MPHTM, FRACP, FRCPA, in the following email Q&A. She discusses which criteria were most critical for balancing participant safety with clinical relevance, how antimicrobial resistance (AMR) shapes strain exclusion for CHIM development, and next steps toward final challenge strain selection and first-in-human studies.
Contagion: You applied eight selection criteria to over 5800 isolates, ultimately narrowing to 86 candidates and then five strains. Which criteria do you consider most critical for balancing participant safety with clinical relevance?
Williams: “The key safety criteria were absence of AMR and absence of genomic determinants associated with disseminated gonococcal infection. These are critical for participant safety for a first-in-human oropharyngeal gonorrhoea challenge model. Our clinical relevance criteria enabled us to have confidence that the strains selected had contemporary global clinical relevance, providing confidence in the generalisability of the findings arising from the gonorrhoea CHIM.”
Contagion: Your analysis highlights the importance of AMR in strain exclusion. Based on your findings, how significant is the AMR challenge for advancing controlled human infection models in gonorrhoea research?
What You need To Know
For first-in-human oropharyngeal CHIM, excluding strains with clinically significant antimicrobial resistance and genomic markers of disseminated infection is essential for participant safety.
A predefined, eight-criterion workflow integrating clinical history, phenotype, and whole-genome data identifies strains that reflect current global circulation and are suitable for evaluating present and future vaccines.
Shortlisted strains representing distinct phylogenetic groups and anatomic sources will undergo detailed phenotypic characterization before a single challenge strain is finalized, with CHIM launch targeted after ethics approval.
Williams: “Exclusion of strains with AMR was a key safety criterion for our strain selection. However, the challenge of gonorrhoea AMR is a key motivator for our research team, as it highlights the critical need novel treatment and prevention strategies for gonorrhoea, which we aim to advance using this gonorrhoea CHIM.”
Contagion: Looking ahead, what are the next steps in moving from this genomics-based selection to final challenge strain development and eventual CHIM studies?
Williams: “The final challenge strain development is well underway, with the results of final strain selection and cell bank manufactures [manufacture] expected by the end of 2025. We aim to undertake our first CHIM study in 2026 after our study protocol has received approval by our local human research ethics committee.”
The approach addresses a key gap in gonorrhea research. Oropharyngeal infection contributes meaningfully to transmission and resistance, yet its pathogenesis remains poorly defined. By making strain selection transparent and systematic, the model aims to accelerate prevention and therapeutic strategies while keeping participant safety central.
Limitations include the single-region source of isolates, which may constrain generalizability, and the possibility that resistance and relevance filters could exclude emerging variants of interest. Clinical behavior of the shortlisted strains in a challenge context is not yet known and will be clarified in the phenotypic phase.
Reference
Williams E, Low SJ, Pollock GL, et al. Selecting candidate Neisseria gonorrhoeae strains for oropharyngeal gonorrhoea human challenge: a genomics-based analysis of clinical isolates. Lancet Microbe. 2025;6(9):101105. doi:10.1016/j.lanmic.2025.101105
