Antibodies Recognizing Protective Pertussis Toxin Epitopes Are Preferentially Elicited by Natural Infection versus Acellular Immunization

Abstract

Despite more than 50 years of vaccination, disease caused by the bacterium Bordetella pertussis persists, with rates increasing in industrialized countries over the past decade. This rise may be attributed to several factors, including increased surveillance, emergence of vaccine escape variants, waning immunity in adults, and the introduction of acellular subunit vaccines, which include chemically detoxified pertussis toxin (PTd). Two potently protective epitopes on pertussis toxin (PTx) are recognized by the monoclonal antibodies 1B7 and 11E6, which inhibit catalytic and cell-binding activities, respectively. In order to determine whether the PTx exposure route affects antibody responses to these epitopes, we analyzed sera from 30 adults with confirmed pertussis exposure and from 30 recently vaccinated adults for specific anti-PTx antibody responses and in vitro CHO cell neutralization titers. While overall titers against PTx and the genetically detoxified variant, PTg, containing the R9K and E129G substitutions, were similar in the two groups, titers against specific epitopes depended on the exposure route. Natural infection resulted in significantly higher titers of anti-PTx-subunit 1, 1B7-like, and 11E6-like antibodies, while acellular vaccination resulted in significantly higher titers of antibodies recognizing PTd. We also observed a correlation between in vitro protection and the presence of 1B7-like and 11E6-like antibodies. Notably, chemical detoxification, as opposed to genetic inactivation, alters the PTx tertiary and quaternary structure, thereby affecting conformational epitopes and recognition of PTx by 1B7 and 11E6. The lower levels of serum antibodies recognizing clinically relevant epitopes after vaccination with PTd support inclusion of PTg in future vaccines.Pertussis vaccines, widely introduced as an inactivated whole-cell vaccine in 1950, have been responsible for a dramatic decline in pertussis-related morbidity and mortality but have been unable to eradicate disease despite 95% coverage in many areas. Disturbingly, rates of confirmed pertussis cases in industrialized countries have increased steadily

Phl p 1–Specific Human Monoclonal IgE and Design of a Hypoallergenic Group 1 Grass Pollen Allergen Fragment

“…Only one of the Abs recognized the C-terminal fragment of Phl p 1, which is immunodominant in humans, and it recognized an epitope different from those recognized by human IgE, as defined by alanine scanning mutagenesis. This suggests that there may be differences in epitopes targeted by Abs derived from naturally developed repertoires and Abs produced by immunization, as previously reported in several other systems (43)(44)(45)(46)(47). Such differences could potentially be explained by a combination of biological processes and technical variations.…”

The Bordetella Adenylate Cyclase Repeat-in-Toxin (RTX) Domain Is Immunodominant and Elicits Neutralizing Antibodies

“…Finally, to determine whether humans show a similar bias toward RTX recognition, we tested nine serum samples from humans exposed to B. pertussis, selected randomly from a larger collection (62). All nine sera recognized RTX 751 at a similar level as full-length ACT, whereas sera from only one individual bound CAT 400 (Fig.…”

Antibody nanoparticle dispersions formed with mixtures of crowding molecules retain activity and In Vivo bioavailability

“…To determine the concentration of active 1B7 in serum samples, a standard ELISA approach was used with the following modifications as previously reported 18,40 . ELISA plates were coated with PTx at 1.5 μg/ml in PBS.…”