CpG 1018® adjuvant enhances Tdap immune responses against Bordetella pertussis in mice

Bordetella pertussis is the causative agent of whooping cough (pertussis), a severe respiratory disease that can be fatal, particularly in infants. Despite high vaccine coverage, pertussis remains a problem because the currently used DTaP and Tdap vaccines do not completely prevent infection or tran...

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Bibliographic Details
Published in:Vaccine 2022-08, Vol.40 (35), p.5229-5240
Main Authors: DeJong, Megan A., Wolf, M. Allison, Bitzer, Graham J., Hall, Jesse M., Sen-Kilic, Emel, Blake, Jeanna M., Petty, Jonathan E., Wong, Ting Y., Barbier, Mariette, Campbell, John D., Bevere, Justin R., Damron, F. Heath
Format: Article
Language:English
Subjects:
Adjuvants
Animal models
Antibodies
Antigens
Bordetella pertussis
CpG 1018
Gene expression
Hemagglutinins
Immune clearance
Immune response
Immunogenicity
Immunoglobulin G
Lymphocytes T
Opsonization
Pathogens
Pertussis
Pertussis mouse model
Pertussis toxin
Phenotypes
Phenotyping
Respiratory diseases
Respiratory tract
Tdap
Tetanus
Toxins
Vaccines
Virulence
Whooping cough
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Summary:Bordetella pertussis is the causative agent of whooping cough (pertussis), a severe respiratory disease that can be fatal, particularly in infants. Despite high vaccine coverage, pertussis remains a problem because the currently used DTaP and Tdap vaccines do not completely prevent infection or transmission. It is well established that the alum adjuvant is a potential weakness of the acellular vaccines because the immunity provided by it is short-term. We aimed to evaluate the potential of CpG 1018® adjuvant to improve antibody responses and enhance protection against B. pertussis challenge in a murine model. A titrated range of Tdap vaccine doses were evaluated in order to best identify the adjuvant capability of CpG 1018. Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), or the whole bacterium were increased due to the inclusion of CpG 1018. In B. pertussis intranasal challenge studies, we observed improved protection and bacterial clearance from the lower respiratory tract due to adding CpG 1018 to 1/20th the human dose of Tdap. Further, we determined that Tdap and Tdap + CpG 1018 were both capable of facilitating clearance of strains that do not express pertactin (PRN-), which are rising in prevalence. Functional phenotyping of antibodies revealed that the inclusion of CpG 1018 induced more bacterial opsonization and antibodies of the Th1 phenotype (IgG2a and IgG2b). This study demonstrates the potential of adding CpG 1018 to Tdap to improve immunogenicity and protection against B. pertussis compared to the conventional, alum-only adjuvanted Tdap vaccine.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2022.07.030