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Clinical Trial
. 2022 Jun 15;40(27):3721-3726.
doi: 10.1016/j.vaccine.2022.04.054. Epub 2022 May 13.

Phase 1/2 clinical trial of COVID-19 vaccine in Japanese participants: A report of interim findings

Satoshi Iwata  1 , Takuhiro Sonoyama  2 , Akari Kamitani  2 , Risa Shibata  2 , Tomoyuki Homma  3 , Shinya Omoto  3 , Kenji Igarashi  2 , Mari Ariyasu  4
Affiliations
Clinical Trial

Phase 1/2 clinical trial of COVID-19 vaccine in Japanese participants: A report of interim findings

Satoshi Iwata et al. Vaccine. .

Abstract

We initiated a randomized, placebo-controlled, phase 1/2 trial to evaluate the safety and immunogenicity of the S-268019-b recombinant protein vaccine, scheduled as 2 intramuscular injections given 21 days apart, in 60 randomized healthy Japanese adults. We evaluated 2 regimens of the S-910823 antigen (5 μg [n = 24] and 10 μg [n = 24]) with an oil-in-water emulsion formulation and compared against placebo (n = 12). Reactogenicity was mild in most participants. No serious adverse events were noted. For both regimens, vaccination resulted in robust IgG and neutralizing antibody production at days 36 and 50 and predominant T-helper 1-mediated immune reaction, as evident through antigen-specific polyfunctional CD4+ T-cell responses with IFN-γ, IL-2, and IL-4 production on spike protein peptides stimulation. Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted.

Keywords: COVID-19 vaccine; Cellular immunity; Clinical trial; Immunogenicity; Reactogenicity; Recombinant protein; Safety.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SI received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, and educational events from Astellas Pharma Inc., Japan Vaccine Co., Ltd., Meiji Seika Pharma Co., Ltd., Pfizer Japan Inc., and Taisho Toyama Pharmaceutical Co. Ltd. TS, AK, RS, TH, SO, KI, and MA are employees of Shionogi & Co. Ltd..

Figures

Fig. 1
Fig. 1
Vaccine regimen and key assessments.
Fig. 2
Fig. 2
Geometric mean titers in the placebo and vaccine groups for (A) anti-spike protein IgG and (B) neutralizing antibody responses. CI, confidence interval; GMT, geometric mean titer; LLOQ, lower limit of quantification. Data are presented as GMTs and 95% CIs. The bars represent the GMT and 95% CI; closed circles represent individual titers. Titer values reported as below the LLOQ are replaced by 0.5 × LLOQ.
Fig. 3
Fig. 3
Immunologic assays for (A) Percent CD4/CD8 cells positive for IFN-γ, IL-2, IL-4, and IL-5 at different time points for the study groups with mean (horizontal bar) and 95% confidence interval (vertical bar) and (B) IFN-γ spots per million PBMCs at different time points for the study groups with mean (triangle) and standard deviation (bar). IFN- γ, interferon gamma; IL, interleukin; PBMC, peripheral blood mononuclear cell.
Supplementary figure 1
Supplementary figure 1
Participant flow.
Supplementary figure 2
Supplementary figure 2
Geometric mean titers for neutralizing antibodies in human convalescent serum data from recovered COVID-19 patients. CI, confidence interval; COVID-19, Coronavirus disease 2019; GMT, geometric mean titer; LLOQ, lower limit of quantification; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. Data are presented as GMTs and 95% CIs. The bars represent the GMT and 95% CI; closed circles represent individual titers. Titer values reported as below the LLOQ are replaced by 0.5 × LLOQ.
Supplementary figure 3
Supplementary figure 3
Representative flow cytometry plots of cytokine-producing CD4+ and CD8+ T cells from a participant in the 10-μg dose cohort on Day 36 exposed to overlapping peptide pools of SARS-CoV-2 S and epitope peptides. IL, interleukin; IFN- γ, interferon gamma; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
See this image and copyright information in PMC

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