14 Jan Duke-NUS Study Finds T-Cells Protect Against Acute Viral Infection
MedicalResearch.com Interview with:
Prof. Ooi Eng Eong
Professor Ooi Eng Eong
Emerging Infectious Diseases Programme
Duke-NUS Medical School
and Shirin Kalimuddin
Assistant Professor and Senior Consultant
Department of Infectious Diseases
Singapore General Hospital and a faculty member of the
Emerging Infectious Diseases Programme at
Duke-NUS Medical School
MedicalResearch.com: What is the background for this study?
Response: The recent pandemic taught us the importance of T cells to protect against COVID-19, especially severe disease. Indeed, where SARS-CoV-2 antibody titres have been too low to neutralise new variants of concern, there is now sizeable evidence that T cells can serve as the correlate of protection against symptomatic infection. However, most working on developing or applying vaccines to prevent diseases such as dengue, continue to focus on measuring antibodies. The goal of this study was thus to determine the extent to which T cells, in the absence of neutralising antibodies, can control infection and hence disease.
We thus took advantage of two other viruses that are genetically related to dengue virus, with licensed vaccines that allow us to probe the effectiveness of T cells in controlling infection. The two vaccines are the live attenuated yellow fever vaccine and the Japanese encephalitis/yellow fever chimeric vaccine. The latter vaccine was constructed using the yellow fever vaccine as the genetic backbone but bearing the genes that encode the Japanese encephalitis viral membrane and envelope proteins. As neutralising antibodies target the envelope protein, vaccination with one vaccine would produce antibodies that would not neutralise the second vaccine. However, the T cell response, which mostly target the other proteins that remain common in both vaccine strains, would be identical.
MedicalResearch.com: What are the main findings?
Response: We found that T cells produced by yellow fever vaccination, when present at high levels , controlled Japanese encephalitis vaccine infection, even to the point of complete aviremia and no seroconversion to Japanese encephalitis. What was remarkable was that this T cell-mediated viral control occurred without neutralising antibodies. Aviremia and lack of seroconversion, conventionally interpreted as sterilising immunity, has until now been universally attributed to neutralising antibodies.
MedicalResearch.com: What should readers take away from your report?
Response: T-cell immunity should not be neglected when designing and evaluating vaccines. This is particularly pertinent for viral diseases such as dengue where vaccine-induced neutralising antibodies may wane and not only be inadequate for protection, but potentially also enhance disease.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: T cells protect against acute viral infection.
MedicalResearch.com: Is there anything else you would like to add? Any disclosures?
Response: We need to develop simple, scalable and quality-assured T cell assays for use in vaccine studies.
Citation: Kalimuddin, S., Tham, C.Y.L., Chan, Y.F.Z. et al. Vaccine-induced T cell responses control Orthoflavivirus challenge infection without neutralizing antibodies in humans. Nat Microbiol (2025). https://doi.org/10.1038/s41564-024-01903-7
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Last Updated on January 14, 2025 by Marie Benz MD FAAD