What is this publication about?

Researchers used a repeated controlled human infection (CHI) with the parasitic worm Schistosoma mansoni to better understand how the immune system develops during worm infections. They compared the immune response of volunteers in a controlled human infection study with that of naturally infected Ugandan individuals, exploring how sex of the worm (exposure to female or male larvae) shapes the immune response.

The main advantage of using a CHI model is the ability to have precise information on the infection dose, sex, and timing. Using all this information, researchers were able to closely follow immune changes to reinfection over time. Some of the key findings from this study include:

• Among the infected CHI volunteers, those who were sequentially exposed to the male and then the female larvae showed a heightened and more acute immune reaction, likely due to potential egg production and/or proteins associated with the female worm.

• The immune response of the volunteers exposed to male larvae only was most similar to the immune response during natural infection (which usually involves both male and female larvae) in the individuals in Uganda.

• The repeated CHI model did not result in protective immunity against re-infection.

Why is this important?

By comparing a controlled human infection model and natural infection in endemic regions, the researchers have demonstrated how immune responses can develop during repeated S. mansoni infection/treatment cycles.

Beyond advancing scientific understanding, CHI models can also provide important information to assess the efficacy of potential future vaccines against worm infections. Understanding the differences in immune responses between non-endemic CHI and endemic infection is critical for inferring how translatable vaccine studies conducted in non-endemic CHI are to the endemic setting. In this study, for example, the researchers demonstrated that worm-specific responses after repeated CHI with male larvae broadly resemble those of naturally infected endemic participants. However, immunological differences remain, highlighting the importance of transferring the CHI model to an endemic area. This kind of research would be a critical next step toward gaining a holistic understanding of how prior exposure, co-infections, immune regulation, and repeated treatment may influence host responses.

How can this make a difference?

This study advances the understanding of the immunology of schistosome (re)infection in humans. In parasitic worm infections, immunity generally develops slowly, and re-infections are common, especially in endemic regions where there is repeated exposure. A better understanding of how immunity develops and which factors influence this process helps researchers develop new treatment or prevention tools, including vaccines.

Infections with parasitic worms continue to cause a massive health burden: more than a billion people suffer from the debilitating effects of infections with such parasites, including schistosomes and hookworms. Vaccines, as an extremely powerful public health intervention with a highly cost-effective impact, could help control and eliminate parasitic worm infections.