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.

Conditions

• Infectious Disease
• Yellow Fever
• Japanese Encephalitis
• Viral Infection

Interventions

BIOLOGICAL

Stamaril

Stamaril is licensed by the Health Sciences Authority (HSA), Singapore. The vaccine are manufactured by Sanofi Pasteur and sourced from Sanofi Pasteur's local distributor.

BIOLOGICAL

Imojev

Imojev is licensed by the Health Sciences Authority (HSA), Singapore. The vaccine are manufactured by Sanofi Pasteur and sourced from Sanofi Pasteur's local distributor.

BIOLOGICAL

Ixiaro

Ixiaro is licensed by the Health Sciences Authority (HSA), Singapore. The Ixiaro vaccines are manufactured by Valneva and sourced from local distributor, Aenon Pharmaceuticals SEA Pte Ltd.

Sponsors & Collaborators

• Duke-NUS Graduate Medical School

  collaborator OTHER

• Singapore General Hospital

  lead OTHER

Principal Investigators

• Shirin Kalimuddin, MRCP (UK) · Singapore General Hospital

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

21 Years

Max Age

45 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-09-28

Primary Completion

2025-10-31

Completion

2025-10-31

Countries

• Singapore

Study Locations