A ground-breaking study involving Kenyan sex workers has shone a light into the immune response to gonorrhoea, paving the way for more effective vaccines.
microarray candidate illustration of a raw microarray scan Each spot is an antibody reacting with a specific antigen or protein from the bacterium. Image Credit: The University of Manchester
Carried out by scientists at the Universities of Manchester and Oxford working in collaboration with the KEMRI/Wellcome Trust Unity in Kenya, the study is published in the journal Nature Communications and funded by the Wellcome Trust.
The findings come amid recent reports showing Gonorrhoea - a sexually transmitted disease - is becoming increasingly resistant to antibiotics and could become untreatable in the future.
People infected with gonorrhoea may experience pain or burning though, if untreated, they may go on to develop more serious problems including infertility, systemic infection and increased risk of HIV/AIDS.
There are now multidrug resistant strains of the Neisseria gonorrhoeae (Ng) bacterium - which causes gonorrhoea - making many antibiotics ineffective as first-line treatments.
The bacterium has a range of mechanisms to dampen immune responses, meaning there is insufficient immunological ‘memory’ to combat subsequent infections.
Attempts to develop a vaccine against gonorrhoea have been largely unsuccessful; however, in 2017 a study showed that vaccination against a related bacterium Neisseria meningitidis (Nm) led to a reduction in the incidence of gonorrhoea.
Although the efficacy of the Nm vaccine against Ng was limited, it provided an important clue to making an effective Ng vaccine.
Working with a marginalized community of sex workers in coastal Kenya who have high exposure to gonorrhoea, Prof Ed Sanders and his team in Kenya conducted a trial of an Nm vaccine to examine their immune responses.
Prof Jeremy Derrick and the team in Manchester then identified the pattern of antibody responses in the vaccine recipients and compared them to individuals infected with gonorrhoea.
To unpick the complicated antibody responses, the Manchester team fabricated a ‘microarray’- a library of the different components, or antigens, which could react with the antibodies induced by the Nm vaccine.
Using this powerful technology, the complex profiles of antibodies against the different components were determined for each vaccinee, or each infected individual.
Comparison of the profiles revealed a detailed picture of the antibody responses to the vaccine, and showing how they differ to those following infection.
The project lead Professor Chris Tang from The University of Oxford said: “This work takes an important step along the road to developing Ng vaccines, as we have a better idea of which responses are generated by partially protective vaccination compared with infection.”
This study has wide implications about revisiting vaccine design for other bacterial pathogens using these new methods, including those where antimicrobial resistance is a problem.
We hope that the application of these technologies will enable progress towards vaccines against other pathogens.”
Prof Jeremy Derrick, The University of Manchester
Source:
Journal reference:
Stejskal, L., et al. (2024). Profiling IgG and IgA antibody responses during vaccination and infection in a high-risk gonorrhoea population. Nature Communications. doi.org/10.1038/s41467-024-51053-x.
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