Differences in epitope‐specific antibodies to pertussis toxin after infection and acellular vaccinations

Abstract

Objectives Pertussis toxin (PT) is a component of all acellular pertussis vaccines. PT must be detoxified to be included in acellular vaccines, which results in conformational changes in the functional epitopes of PTs. Therefore, induced epitope‐specific antibodies to PT may vary after vaccinations or natural infections, and this information could reveal biomarkers implicated for protection and successful immunisation. Methods Pertussis toxin epitope‐specific antibodies in sera from 152 vaccinated children and 72 serologically confirmed patients were tested with a blocking ELISA, based on monoclonal antibodies that target protective PT epitopes. Results All study groups induced considerable antibody titres to subunit 1 (S1). Of interest, S3 7E10‐specific antibodies were present in patients, but not after vaccinations (P < 0.001). The impact of glutaraldehyde treatment of PT was visible on epitope 1D7 (S1), whereas epitopes 1B7 (S1) and 10D (S1) were more preserved. Antibodies to these epitopes were higher after three primary vaccine doses than after a single booster dose. Conclusion The high amount of 7E10‐specific antibodies in patients suggests this epitope might be functionally relevant in protection. The overall characteristics of epitope‐specific antibodies are influenced by infection or vaccination background, by the used detoxification method of PT and by the amount of the toxin used in immunisation.

Evaluation of Anti-PT Antibody Response after Pertussis Vaccination and Infection: The Importance of Both Quantity and Quality

“…The connection between antibody-mediated neutralization of specific PT epitopes and protection from disease by human antibodies has not been studied extensively. Thus far, a deficit of vaccination-induced epitope-specific antibodies in comparison to infection was reported in studies by Sutherland et al, and Knuutila et al, by competitive ELISAs towards epitopes 1B7 and 1D7 in S1,11E6 in S23, and 7E10 in S3, which were identified with Mabs originally isolated from mouse [ 5 , 31 , 106 , 107 , 108 ]. After infection, antibodies binding the epitope recognized by the 7E10 Mab in particular appeared in substantial amounts and correlated with the overall anti-PT IgG titers, whereas children who received ACVs had much lower and non-correlative levels of 7E10-like antibodies regardless of dose amounts or detoxification treatment [ 31 ].…”

“…A similar observation regarding the 11E6 epitope was established in both studies. The presence of S1 epitopes was more vaccine-dose dependent: single doses of ACVs had fewer epitope-specific antibodies than infection, whereas three consecutive ACV doses in babies induced at least an equal amount of S1 antibodies as infection [ 31 , 106 ].…”

“…No extensive epitope mapping exists today for antibody response in humans. For example, we have rather poor insight if ACVs skew the immune response to non-protective epitopes [ 31 ]. Likewise, WCV-induced epitope-specific antibody responses have not been studied [ 116 ].…”

“…These methods include, e.g., the neutralization of leukocytosis-promoting activity, antibody-mediated opsonophagocytosis [ 26 ], and importantly the measurement of the neutralization capacity of anti-PT antibodies, which can be evaluated by the antibodies’ ability to prevent the clustering of Chinese hamster ovary cells [ 27 , 28 , 29 ]. Other general aspects, such as the affinity of antibodies and their specific binding locations to PT, may act as contributive factors in the antibodies’ potency to neutralize and clear out the toxin [ 30 , 31 ]. In addition, it is crucial to understand the true nature of the machinery to produce these antibodies such as B cell populations, including memory B cells (Bmem), behind the antibody production and how they change during the lifespan [ 32 , 33 ].…”