Bordetella pertussis elicits both innate and adaptive cellular responses, yet their relative contributions to peripheral interferon-γ (IFN-γ) measurements and the temporal dynamics of circulating T-cell reactivity in adults remain incompletely defined. B. pertussis-reactive cellular immunity was investigated in 42 adult donors, including 26 healthy donors and 16 donors with a history of pertussis, using standard and modified IFN-γ enzyme-linked immunospot (ELISpot) assays with a chemically inactivated whole-cell B. pertussis preparation, bacterial innate-biased stimuli, and a peptide-based T-cell recall control, together with human leukocyte antigen A*02 (HLA-A*02) genotyping. Short-term stimulation of unfractionated peripheral blood mononuclear cells (PBMCs) generated readily detectable IFN-γ spot formation that was not clearly stratified by childhood vaccination background or previous pertussis history. In a subset of seven donors, lipopolysaccharide and B. pertussis-derived lipooligosaccharide generated strong total PBMC signals but little detectable pattern-defined T-cell-associated spot formation, whereas the whole-cell pertussis preparation retained a detectable T-cell-associated component under modified assay conditions. Among seven donors available for longitudinal follow-up after pertussis, pattern-defined T-cell-associated IFN-γ spot frequencies in peripheral blood were highest at the recovery sampling point, were significantly reduced at one month, decreased further by three months, remained markedly reduced at six months, and approached background levels at 12 months after recovery. Directly measured CD8+ IFN-γ responses were preferentially detected in HLA-A*02-positive donors. These findings indicate that cellular composition and sampling time affect the interpretation of peripheral IFN-γ responses to B. pertussis and show an association between HLA-A*02 status and detectable CD8+ reactivity.

Гуморальный иммунный ответ на линейные и конформационные эпитопы SARS-CoV-2 у пациентов с COVID-19

Whooping cough is a serious illness affecting young children. There are two main types of vaccines for whooping cough: cellular and acellular. We focused on studying the immune response to Bordetella pertussis based on the type of vaccination to uncover factors that affect vaccine effectiveness. It is worth noting that the immune response to Bordetella pertussis depends on many factors. In this study, we examine the role of the systemic T cell response. It was found that memory T cells react to components of the pertussis bacterium, and the strength of this response is independent of the vaccination type. In most donors, the T cell response to the inactivated bacterium was more robust than to gd15PtxS1 (genetically detoxified S1 subunit of pertussis toxin), a key ingredient in acellular vaccines. This indicates the existence of dominant epitopes beyond PT that elicit an immune response. Additionally, a bioinformatics analysis was conducted on the epitopes of various B. pertussis proteins, predicting their dominance based on HLA alleles and assessing the potential for cross-reactive T cell responses to other Bordetella species and human microbiota. These findings could help in the development of new vaccines against B. pertussis or in modifying existing vaccines to improve their efficacy and minimize side effects. These results may help in the development of new vaccines against B. pertussis or in the modification of vaccines to their efficacy and minimize side effects.

Bordetella pertussis, a gram-negative bacterium responsible for whooping cough, poses severe health risks, especially to young children. However, the disease can be prevented by immunization with whole-cell pertussis vaccines and acellular pertussis vaccines containing 2–5 purified B. pertussis antigens, of which chemically detoxified pertussis toxin is the main protective component. While current vaccines have proven effective, concerns over high reactogenicity of whole-cell pertussis vaccines and the waning immunity to acellular pertussis vaccines formulations underscore the need for improved pertussis vaccines. Genetically detoxified pertussis toxin is an attractive vaccine candidate because it retains most of the structural properties of native pertussis toxin and better preserves the protective epitopes compared to detoxified pertussis toxin. In this study, we developed a candidate vaccine based on a genetically detoxified pertussis toxin S1 subunit, gd15PTxS1. We evaluated humoral and cellular immunogenicity of gd15PTxS1 in a murine model and demonstrated significant anti-PTx IgG seroconversion and a balanced Th1/Th2/Th17 T-cell response, with gd15PTxS1 inducing robust cytotoxic and helper T-cell activation comparable to that of the whole-cell pertussis vaccines. Our results show that gd15PTxS1 is highly immunogenic in mice and is a promising vaccine candidate for further protectivity studies.

Bordetella pertussis elicits both innate and adaptive cellular responses, yet their relative contribution to peripheral IFN-γ measurements and the temporal behavior of circulating T-cell immunity in adults remain incompletely defined. We investigated B. pertussis-reactive cellular immunity in peripheral blood in healthy and convalescent adult donors using IFN-γ ELISpot assays after stimulation with whole-cell B. pertussis or bacterial components (LPS and B. pertussis-derived LOS), and HLA-A02 genotyping. Short-term stimulation of unfractionated PBMCs produced a prominent IFN-γ response that was not clearly associated with previous vaccination or pertussis history. LOS and LPS induced strong responses in PBMCs but little detectable IFN-γ secretion by T cells, whereas whole-cell B. pertussis retained T-cell-associated IFN-γ response. Circulating B. pertussis-reactive T-cell responses were highest after recovery, declined substantially within approximately 3 months, and approached baseline by ≥1 year. CD8+ IFN-γ responses were preferentially detected in HLA-A*02-positive donors. These findings indicate that adult peripheral immunity to B. pertussis comprises cellularly and temporally distinct IFN-γ-producing components and that cellular context, time after infection, and HLA class I genotype influence their detection and interpretation.