Assessment of safety and efficacy against Bordetella pertussis of a new tetanus-reduced dose diphtheria-acellular pertussis vaccine in a murine model

Abstract

BackgroundTetanus-reduced dose diphtheria-acellular pertussis (Tdap) vaccination during adolescence was introduced in response to the resurgence of pertussis in various countries. A new Tdap vaccine was manufactured in Korea as a countermeasure against a predicted Tdap vaccine shortage. This study was performed to evaluate the immunogenicity, safety, and protection efficacy against Bordetella pertussis of the new Tdap vaccine in a murine model.MethodsFour-week-old BABL/c mice were used for assessment of immunogenicity and protection efficacy. A single dose of primary diphtheria-tetanus-acellular pertussis (DTaP) vaccine was administered, followed by a single dose of Tdap booster vaccine after a 12-week interval. Anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), and anti-pertactin (PRN) IgG titers were measured before primary vaccination, and before and after booster vaccination. An intranasal challenge test was performed after booster vaccination to determine protection efficacy. To assess safety, mouse weight gain test and leukocytosis promotion test were performed using 4-week-old ddY female mice.ResultsAnti-PT and anti-FHA IgG titers after booster vaccination were significantly higher than those before booster vaccination with either the new vaccine or a commercially available Tdap vaccine (P = 0.01 for all occasions). After booster vaccination, no significant difference was observed between the two vaccines in antibody titers against pertussis antigens (P = 0.53 for anti-PT IgG, P = 0.91 for anti-FHA IgG, P = 0.39 for anti-PRN IgG). In the intranasal challenge test, inoculated B. pertussis was eradicated 7 days after infection. On days 4 and 7 after infection, colony counts of B. pertussis were not significantly different between the new and positive control vaccine groups (P = 1.00). Mean body weight changes and leukocyte counts of the new vaccine, positive control, and negative control groups were not significantly different 7 days after vaccination (P = 0.87 and P = 0.37, respectively). All leukocyte counts in the new vaccine group were within a mean ± 3 standard deviations range.ConclusionsA murine model involving a single dose primary DTaP vaccination followed by a single dose Tdap booster vaccination can be used for non-clinical studies of Tdap vaccines. The new Tdap vaccine manufactured in Korea exhibited comparable immunogenicity, protection efficacy, and safety with a commercially available Tdap vaccine.

The Adjuvant Bordetella Colonization Factor A Attenuates Alum-Induced Th2 Responses and Enhances Bordetella pertussis Clearance from Mouse Lungs

“…on days 0 and 28 with 1/5 the human dose of Boostrix alone or mixed with 30 g BcfA and then were challenged intranasally with Bp536 on days 12 to 14 postboost. We selected this dose of aPV since it has been used by others to test vaccine-induced immune responses in mice (20)(21)(22)(23). Bacterial colonies in the lungs were enumerated on days 1, 4, 7, and 14 postchallenge.…”

Immunogenicity of a New Enhanced Tetanus-reduced Dose Diphtheria-acellular Pertussis (Tdap) Vaccine Against Bordetella Pertussis in a Murine Model

“…Since 2000, a serological study in Korea has con rmed incidents of pertussis infection with higher certainty than reported earlier, and small-scale pertussis outbreaks have occurred once every 3 years since 2009, leading to the requirement for Tdap vaccination. In 2010, GC Pharma, a national company, started developing Tdap and DTaP vaccines; and our laboratory, the Vaccine Bio Research Institute, conducted animal-based studies [11,12] and performed clinical trials [13] using the Tdap booster vaccine. In animal studies, GC Pharma's new Tdap vaccine, GC3111, was compared with Boostrix™, a commercially available product in Korea.…”

“…In animal studies, GC Pharma's new Tdap vaccine, GC3111, was compared with Boostrix™, a commercially available product in Korea. The humoral immunity was assessed after a single dose of DTaP vaccine followed by Tdap booster vaccine [12], and CMI was assessed after two doses of DTaP vaccine followed by Tdap booster vaccine [11]. After two animal studies and clinical trials, GC Pharma complemented GC3111 to improve the anti-FHA antibody response.…”

“…All mice were vaccinated with one-fourth of the human dose (0.125 mL) via intramuscular (quadriceps muscle) injection and immunized with two doses of primary diphtheria-tetanus-acellular pertussis (DTaP) vaccine (provided by GC Pharma) at 3-week intervals, except for the negative control group, which was vaccinated with saline before booster vaccination. The study was conducted according to previous murine model studies at our laboratory at the Vaccine Bio Research Institute [11][12]. All Tdap vaccine components were equivalent to PT 8 μg, FHA 8 μg, and PRN 2.5 μg.…”

Enzyme-linked immunosorbent assay for detecting anti-pertussis toxin antibody in mouse

“…In Korea, legislation for the vaccination of diphtheria-tetanus-pertussis vaccine was established in 1954, and the diphtheria, tetanus toxoids, whole-cell pertussis (DTwP) vaccine was used for vaccination until the early 1980s. A two-pertussis antigen (pertussis toxoid [PT] and filamentous hemagglutinin [FHA])-containing diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine, which was developed in Japan, was introduced and used in Korea [2]. In the late 1990s, a three-component DTaP vaccine containing PT, FHA, and pertactin was introduced in Korea.…”