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

Publisher: BioMed Central Country of Publication: England NLM ID: 100968551 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2334 (Electronic) Linking ISSN: 14712334 NLM ISO Abbreviation: BMC Infect Dis Subsets: MEDLINE

Original Publication: London : BioMed Central, [2001-

Bordetella pertussis/*immunology ; Diphtheria-Tetanus-acellular Pertussis Vaccines/*immunology ; Whooping Cough/*prevention & control; Antigens, Bacterial/immunology ; Bacterial Outer Membrane Proteins/immunology ; Diphtheria-Tetanus-acellular Pertussis Vaccines/administration & dosage ; Diphtheria-Tetanus-acellular Pertussis Vaccines/adverse effects ; Virulence Factors, Bordetella/immunology ; Animals ; Antibodies, Anti-Idiotypic ; Antibodies, Bacterial ; Dose-Response Relationship, Immunologic ; Female ; Hemagglutinins ; Humans ; Immunization, Secondary ; Immunogenicity, Vaccine ; Mice ; Mice, Inbred C57BL ; Pertussis Toxin ; Republic of Korea

Background: Tetanus-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.
Methods: Four-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.
Results: Anti-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.
Conclusions: A 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.

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Keywords: Diphtheria-tetanus-acellular pertussis vaccine; Efficacy; Immunogenicity; Mice; Safety

0 (Antibodies, Anti-Idiotypic)
0 (Antibodies, Bacterial)
0 (Antigens, Bacterial)
0 (Bacterial Outer Membrane Proteins)
0 (Diphtheria-Tetanus-acellular Pertussis Vaccines)
0 (Hemagglutinins)
0 (Virulence Factors, Bordetella)
0 (anti-IgG)
63GD90PP8X (pertactin)
EC 2.4.2.31 (Pertussis Toxin)

Date Created: 20170406 Date Completed: 20170628 Latest Revision: 20220331

20260130

PMC5381055

10.1186/s12879-017-2369-x

28376777