Antibody avidity to pertussis toxin after acellular pertussis vaccination and infection

ABSTRACT

Pertussis toxin (PT) is a unique virulence factor of Bordetella pertussis, and therefore a key component of acellular pertussis vaccines. Although immunity after infection seems to persist longer than after vaccination, the exact mechanisms are not fully known. In this study the overall binding strength (avidity) of anti-PT IgG antibodies was compared after acellular booster vaccination and infection, as a parameter to evaluate long-lasting protection.

Danish and Finnish serum samples from a total of 134 serologically confirmed patients and 112 children who received acellular booster vaccines were included in this study. The concentration of anti-PT IgG was first determined by ELISA, followed by two separate ELISAs to evaluate antibody avidity: either with a dilution series of urea as a bond-breaking agent of antibody and antigen binding and a constant anti-PT IgG concentration between the samples or with a constant dilution ratio of sera and detergent. In addition to urea, the use of diethylamine and ammonium thiocyanate as disruptive agents were first compared between each other.

A strong Spearman correlation (R > 0.801) was noted between avidity and concentration of anti-PT IgG antibodies if a constant serum dilution method was used, and avidity was noted to be higher in patients in comparison to vaccinees in Denmark, but not in Finland. However, no correlation between antibody concentration and avidity was found if a constant anti-PT IgG concentration was used (R = −0.157). With this method, avidity after vaccination was significantly higher in comparison to that after infection in both Danish and Finnish subjects (p < 0.01). A shorter time since the latest booster vaccination was found to affect avidity positively on the next PT-antigen exposure with either vaccination or infection.

KEYWORDS:

• Pertussis
• pertussis toxin
• avidity
• ELISA
• vaccination

Acknowledgments

The purified PT antigen was kindly provided by GlaxoSmithKline, Belgium. Joonatan Mäkelä (Department of Life Sciences, University of Turku) is acknowledged for his technical support in assay development.

This study was conducted as a part of the PERISCOPE (pertussis correlates of protection Europe) project. The PERISCOPE project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement number 115910. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme; the European Federation of Pharmaceutical Industries and Associations; and the Bill & Melinda Gates Foundation.

Author contributions

Aapo Knuutila: Data curation; Investigation; Methodology; Writing-original draft. Tine Dalby: Investigation; Resources; Methodology; Writing-review & editing. Niina Ahvenainen: Data curation; Investigation; Methodology; Writing-review & editing. Alex-Mikael Barkoff: Investigation; Methodology; Writing-review & editing. Charlotte Sværke Jørgensen: Data curation; Resources; Writing-review & editing. Kurt Fuursted: Data curation; Resources; Writing-review & editing. Jussi Mertsola: Investigation; Resources; Funding acquisition; Writing-review & editing. Qiushui He: Investigation; Methodology; Funding acquisition; Resources; Data curation; Writing-original draft; Writing-review & editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was partly funded by InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530) and Tampereen Tuberkuloosisäätiö [grant number 26005475]. A.K. was paid by a grant from the Alfred Kordelin Foundation (grant decision 28th October 2020) and Juhani Aho foundation for medical research (2020); IMI2 Horizon2020 .