Impact of age and vaccination history on long-term serological responses after symptomatic B. pertussis infection, a high dimensional data analysis

Abstract

Capturing the complexity and waning patterns of co-occurring immunoglobulin (Ig) responses after clinical B. pertussis infection may help understand how the human host gradually loses protection against whooping cough. We applied bi-exponential modelling to characterise and compare B. pertussis specific serological dynamics in a comprehensive database of IgG, IgG subclass and IgA responses to Ptx, FHA, Prn, Fim2/3 and OMV antigens of (ex-) symptomatic pertussis cases across all age groups. The decay model revealed that antigen type and age group were major factors determining differences in levels and kinetics of Ig (sub) classes. IgG-Ptx waned fastest in all age groups, while IgA to Ptx, FHA, Prn and Fim2/3 decreased fast in the younger but remained high in older (ex-) cases, indicating an age-effect. While IgG1 was the main IgG subclass in response to most antigens, IgG2 and IgG3 dominated the anti-OMV response. Moreover, vaccination history plays an important role in post-infection Ig responses, demonstrated by low responsiveness to Fim2/3 in unvaccinated elderly and by elevated IgG4 responses to multiple antigens only in children primed with acellular pertussis vaccine (aP). This work highlights the complexity of the immune response to this re-emerging pathogen and factors determining its Ig quantity and quality.

Bordetella pertussis population dynamics and phylogeny in Japan after adoption of acellular pertussis vaccines

“…The rising percentage of pertussis cases in Japanese teenagers or adults [ 84 ] suggests waning immunity to be one contributing factor, coupled with a vaccination schedule that incorporates a booster at an early age (2 years) but lacks a secondary immunization for adolescents, as championed in the USA [ 2 ]. Recent studies revealed that the level of decrease in vaccine effectiveness against pertussis disease depends on both the specific vaccine antigen and the subject’s age [ 85 ]. As a short-term solution, the efficacy of existing vaccines may be improved by a change in vaccination booster regimens, by an expansion of maternal immunizations or by improving existing ACV antigens.…”

Robust Humoral and Cellular Immune Responses to Pertussis in Adults After a First Acellular Booster Vaccination

“…This is underlined by the fact that the majority of our participants showed pre-booster PT-IgA levels, that further increased post-booster. IgA responses are not induced by aP vaccines in infants ( 22 ), but exposure to B. pertussis induces systemic pertussis-specific IgA-producing memory B-cells in children and adults ( 22 , 33 ). Therefore, the presence of IgA antibodies pre-booster and their rise post-booster may result from the activation of pre-existing pertussis-specific memory B-cells induced by previous B. pertussis contact in life, indicative of enhanced B. pertussis circulation nowadays.…”

Multiplex Point-of-Care Tests for the Determination of Antibodies after Acellular Pertussis Vaccination

“…This was likely due to the unspecific binding of the protein-A label to the IgA and IgM antibodies from the samples, as a test with anti-human IgG label conjugate (Figure 3) produced no signal with the same samples from the PT test line. (16,17), (g) both PRN and FHA positive, (18,19), and (h) all negative samples (1,2,3). Please refer to Table 1 for antibody concentrations.…”

“…Additionally, the simultaneous measurement of IgA, IgG and IgM antibody levels has been reported to provide the most diagnostic accuracy [27], especially if interpreted in connection with clinical findings [28], but may also lead to overdiagnosis [14,29]. Considering IgG subclasses, IgG1 and 4 responses were elevated to multiple antigens in children primed with acellular pertussis vaccines [17,[30][31][32], whereas, in patients or unvaccinated convalescent children, IgG1 and IgG3 were more prevalent [30,31,33]. Therefore, the multiplexing of IgG1, 3 and 4 could provide a more comprehensive image to separate recent vaccination and infection.…”

“…ELISAs are time-consuming and laborious, and pose limitations when the volume of serum samples may be limited when required to quantify the immune response to pathogens presenting multiple virulence factors. Cost-efficient and high-throughput multiplex serological assays in the pertussis field already have a broad application [16][17][18][19]. We have reported earlier on a simple, quantitative and rapid lateral flow (LF)-based platform for anti-PT IgG serological diagnostics of pertussis without the complexity of common laboratory practicalities [20].…”