Pertussis or whooping cough is a human respiratory tract infection caused by Bordetella pertussis bacteria. Despite extensive vaccinations, pertussis incidence has increased during the last decades. The reasons behind this resurgence are not entirely understood. Multiple factors may influence the resurgence, such as improved diagnostic methods, the adaptation of circulating B. pertussis strains, the waning of vaccination-induced immunity, and asymptomatic pathogen transmission.

The shift from whole-cell to acellular pertussis vaccines (aPV) has been speculated as one of the reasons for the quickly waning vaccination-induced immunity. The reduced reactogenicity of the aPVs is achieved by chemically treating the vaccine components. The treatments alter the structure of the vaccine antigens and may affect the functional properties of antibodies generated after vaccination.

Currently, no internationally established immunological correlates of protection exist for evaluating pertussis vaccine-induced protection. This study compared the antibody responses to pertussis toxin (PT) after aPV and infection. PT is an exotoxin that can elicit many biological activities and is included in all current aPVs. Binding strength, binding location, and the neutralizing activity of these antibodies were evaluated with newly developed immunoassays for patient and vaccination samples in Finnish, Danish, and Dutch populations.

Infection and aPV-derived antibodies recognized different epitopes of PT. The binding strength of antibodies was higher after aPVs compared to infection. Elevated concentrations of PT-neutralizing antibodies remained one year after aPV. These characteristics were influenced by the detoxification method of PT, amount of PT included in aPV, number of vaccination doses received, existing immunological memory of PT, and recency of the latest vaccination. The studied antibody characteristics may contribute as potential correlates of protection and thus aid the evaluation of the next generation of vaccines, vaccination programs, and diagnostics.