News & Views by KU Leuven: T cell-mediated protection in absence of virus neutralizing antibodies

Yeranddy A. Alpizar & Kai Dallmeier

Nature Microbiology

Published: January 23rd, 2025 (Commentary)

Researchers from KU Leuven published a commentary on a clinical trial conducted at Duke-NUS Medical School, Singapore published recently in the same journal. This study has the potential to change the way we should think about antiviral vaccines. The team from Singapore conducted a controlled human challenge study using licensed YF17D and chimeric JE/YF17D vaccines replicating earlier preclinical results, including from KU Leuven, that clearly demonstrate that such potent vaccines can induce T cells, a type of white blood cell, which may suffice to prevent subsequent viral infections without the need of specific virus neutralizing antibodies. Such neutralizing antibodies are traditionally seen as essential for immunity, as they bind to viruses and prevent them from infecting cells, this study challenges this notion.

Key Concepts

✅ T Cells Can Control Infection Without Antibodies: The highlighted findings showed that T cell responses, triggered by vaccination by either life vaccine, may be sufficient to control infection by the other, lowering viral loads and reducing symptoms, even without neutralizing antibodies.

✅ Complete Virus Clearance in Some Participants: Remarkably, some participants cleared the challenge virus completely, with no seroconversion, suggesting T cells alone provided sterilizing immunity at least in the controlled trial setting. 

✅ Previous YF17D Vaccination Offers Protection: Additionally, those previously vaccinated with YF17D had lower JE/YF17D viremia compared to those who had not been previously vaccinated, further highlighting T cell protection.

Implications for Future Vaccines:

These findings underscore the vital role of T cells in antiviral immunity and opens the door for next-generation vaccines that harness T cell responses alongside neutralizing antibodies. Such vaccines could offer broad protection, especially against rapidly mutating viruses where antibody-based immunity may be less effective. Moreover, future vaccine design, testing and approval should consider other parameters than currently dominating plain antibody testing, and be rather guided by the actual molecular and cellular mechanisms involved in protection.

🔗 Read the full publication here: https://doi.org/10.1038/s41564-024-01921-5

Alpizar YA, Dallmeier K. T cell-mediated protection in absence of virus neutralizing antibodies. Nat Microbiol. 2025 Feb;10(2):277-278. doi: 10.1038/s41564-024-01921-5. PMID: 39849084.