An Experimental Medicine Decipher of a Minimum Correlate of Cellular Immunity

Summary

We hypothesize that a high CD4+ and CD8+ T cell count will reduce viremia upon challenge with a structurally heterologous virus, and correspondingly result in reduced magnitude of host response to challenge infection. Primary Objective: To compare, after challenge with a structurally heterologous vaccine, the differences in levels of viremia between healthy adults who received primary vaccination with either YF17D vaccine, chimeric JE-YF17D vaccine, or inactivated JE vaccine. 58 subjects will be randomised into 1 of 2 arms (Arm B1 and Arm B2) in a 1:1 ratio, in a double-blind fashion. Subjects in Arm B1 will receive JE-YF17D vaccine (Imojev, Sanofi Pasteur) on Day 0 followed by YF17D vaccine (Stamaril, Sanofi Pasteur) on Day 28. Subjects in Arm B2 will receive Stamaril on Day 0 followed by Imojev on Day 28. Arm B3 will be conducted as a separate single-arm open label design in 14 subjects. Subjects in Arm B3 will receive inactivated JE vaccine (Ixiaro, Valneva) on Day 0 followed by Stamaril on Day 28. The rationale for these three study arms is as follows: Arm B1 will show the impact low levels of viremia, and the resultant low levels of virus-specific CD4+ and CD8+ T cells, would have on YF17D infection. In contrast, YF17D vaccination in Arm B2 would produce high levels of viremia, and in turn high levels virus-specific T cells, thus likely ameliorating JE-YF17D infection. Arm B3 will serve as the control arm, as vaccination with inactivated JE vaccine would not produce any YF17D-specific T cell response. Notably, the first vaccination in Arms B1 and B2 would also provide the viremia response in the absence of virus-specific T cells, which would serve as a reference point to interpret the outcome of the second vaccination.

Timeline

Start

2022-09-28

Primary completion

2025-10

Completion

2025-10

Publications

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• Kalimuddin S, Tham CYL, Chan YFZ, Hang SK, Kunasegaran K, Chia A, Chan CYY, Ng DHL, Sim JXY, Tan HC, Syenina A, Ngoh AQ, Hamis NZ, Chew V, Leong YS, Yee JX, Low JG, Chan KR, Ong EZ, Bertoletti A, Ooi EE. Vaccine-induced T cell responses control Orthoflavivirus challenge infection without neutralizing antibodies in humans. Nat Microbiol. 2025 Feb;10(2):374-387. doi: 10.1038/s41564-024-01903-7. Epub 2025 Jan 10.
• Kalimuddin S, Chan YFZ, Sessions OM, Chan KR, Ong EZ, Low JG, Bertoletti A, Ooi EE. An experimental medicine decipher of a minimum correlate of cellular immunity: Study protocol for a double-blind randomized controlled trial. Front Immunol. 2023 Mar 10;14:1135979. doi: 10.3389/fimmu.2023.1135979. eCollection 2023.

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