Immunogenicity of a New Enhanced Tetanus-reduced Dose Diphtheria-acellular Pertussis (Tdap) Vaccine Against Bordetella Pertussis in a Murine Model
Background
The necessity of the tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccine in adolescence and adults has been emphasized since the resurgence of small-scale pertussis in Korea and worldwide due to the waning effect of the vaccine and variant pathogenic stains in the late 1990s. GreenCross Pharma (GC Pharma), a Korean company, developed the Tdap vaccine GC3111 in 2010. Recently, they enhanced the former vaccine GC3111 to reinforce the antibody response against filamentous hemagglutinin (FHA). In this study, the immunogenicity and efficacy of the enhanced Tdap vaccine were compared and evaluated between the former Tdap vaccine GC3111 and the commercially available Tdap vaccine in a murine model.
Methods
Balb/C mice were primed with two doses of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine followed by a single booster Tdap vaccine at 6 weeks using the commercially available Tdap vaccine or 2 Tdap vaccines from GC Pharma (GC3111, enhanced GC3111). Humoral response was assessed 1 week before and 2 and 4 weeks after Tdap booster vaccination. The INF-γ (Th1), IL-5 (Th2), and IL-17 (Th17) cytokines were assessed 4 weeks after booster vaccination by stimulation with three simulators: heat inactivated Bordetella pertussis (hBp), vaccine antigens, and hBp mixed with antigens. An intranasal challenge test was performed 4 weeks after booster vaccination.
Results
The enhanced GC3111 generated a humoral response to filamentous hemagglutinin (FHA) that was comparable to that of the commercial vaccine. Regarding cell-mediated immunity, cytokine secretion differed among the three simulators. However, no difference was found between the groups. All the vaccinated groups indicated a Th1/Th2 response. The mean value of INF-γ in the control and study groups (simulated with hBp mixed with antigens) was 12,551.69, and the mean value of IL-5 (simulated with antigens) was 1,782.47 pg/mL. On Day 5 post-intranasal challenge, B. pertussis colonies were absent in the lungs in all groups.
Conclusions
Our results confirmed the immunogenicity of GC Pharma’s Tdap vaccine; enhanced GC3111 was equivalent to the presently used commercial vaccine in terms of humoral response as well as cell-mediated cytokine expression.
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This is a list of supplementary files associated with this preprint. Click to download.
Additional file 1: Table S1. Raw data of cell mediated cytokine immune response by cytokine ELISA kit.
Additional file 1: Table S1. Raw data of cell mediated cytokine immune response by cytokine ELISA kit.
Additional file 2: Table S2. B. pertussis clearance was evaluated. The colony forming cells from lungs were counted two times.
Additional file 2: Table S2. B. pertussis clearance was evaluated. The colony forming cells from lungs were counted two times.
Posted 16 Dec, 2020
On 01 Dec, 2020
On 01 Dec, 2020
On 01 Dec, 2020
On 30 Nov, 2020
Immunogenicity of a New Enhanced Tetanus-reduced Dose Diphtheria-acellular Pertussis (Tdap) Vaccine Against Bordetella Pertussis in a Murine Model
Posted 16 Dec, 2020
On 01 Dec, 2020
On 01 Dec, 2020
On 01 Dec, 2020
On 30 Nov, 2020
Background
The necessity of the tetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccine in adolescence and adults has been emphasized since the resurgence of small-scale pertussis in Korea and worldwide due to the waning effect of the vaccine and variant pathogenic stains in the late 1990s. GreenCross Pharma (GC Pharma), a Korean company, developed the Tdap vaccine GC3111 in 2010. Recently, they enhanced the former vaccine GC3111 to reinforce the antibody response against filamentous hemagglutinin (FHA). In this study, the immunogenicity and efficacy of the enhanced Tdap vaccine were compared and evaluated between the former Tdap vaccine GC3111 and the commercially available Tdap vaccine in a murine model.
Methods
Balb/C mice were primed with two doses of the diphtheria-tetanus-acellular pertussis (DTaP) vaccine followed by a single booster Tdap vaccine at 6 weeks using the commercially available Tdap vaccine or 2 Tdap vaccines from GC Pharma (GC3111, enhanced GC3111). Humoral response was assessed 1 week before and 2 and 4 weeks after Tdap booster vaccination. The INF-γ (Th1), IL-5 (Th2), and IL-17 (Th17) cytokines were assessed 4 weeks after booster vaccination by stimulation with three simulators: heat inactivated Bordetella pertussis (hBp), vaccine antigens, and hBp mixed with antigens. An intranasal challenge test was performed 4 weeks after booster vaccination.
Results
The enhanced GC3111 generated a humoral response to filamentous hemagglutinin (FHA) that was comparable to that of the commercial vaccine. Regarding cell-mediated immunity, cytokine secretion differed among the three simulators. However, no difference was found between the groups. All the vaccinated groups indicated a Th1/Th2 response. The mean value of INF-γ in the control and study groups (simulated with hBp mixed with antigens) was 12,551.69, and the mean value of IL-5 (simulated with antigens) was 1,782.47 pg/mL. On Day 5 post-intranasal challenge, B. pertussis colonies were absent in the lungs in all groups.
Conclusions
Our results confirmed the immunogenicity of GC Pharma’s Tdap vaccine; enhanced GC3111 was equivalent to the presently used commercial vaccine in terms of humoral response as well as cell-mediated cytokine expression.
Figure 1
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