Diphtheria Toxoid Particles as Q Fever Vaccine

Abstract

There is an unmet need for a stable and nonreactogenic vaccine against the bioterrorism agent, Coxiella burnetii, causing Q fever. Here a safe, effective, and non‐reactogenic Q fever vaccine is developed by employing self‐assembled particles (CPs) composed of cross‐reacting material 197, a nontoxic variant of diphtheria toxin. CPs are designed that incorporate selected C. burnetii antigens and assemble them inside engineered Escherichia coli at high yields. A cost‐effective manufacturing process enables the production of CP‐based Q fever vaccine candidates. Four vaccine candidates are developed, including a T‐cell epitope‐based vaccine (CP‐COX), and one that comprises two immunodominant antigens, Com1 and YbgF. The latter is tested separately (CP‐Com1, CP‐YbgF) or as a mixture (CP‐Com1/CP‐YbgF). Initial immunogenicity studies in mice reveal that the mixed CP‐Com1/YbgF elicits the highest antibody titers with a half maximal effective concentration (EC50) value of ≈100 000 and induction of TH1 and TH2 cytokines. CP‐Com1/YbgF is further evaluated in guinea pigs, demonstrating its safety and efficacy, as shown by the absence of adverse reactions and a significant reduction in febrile responses compared to alum upon challenge with C. burnetii. Together, the study shows the potential of CPs for the development of a safe and immunogenic subunit Q fever vaccine.

Intranasal Epitope‐Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus

“…Similar thermostability studies with BPbased vaccines against COVID-19, group A Streptococcus, and Q Fever also demonstrated the stability of BP-based vaccines in terms of protein profiles, protein band intensity, particle sizes, and zeta potentials at different temperatures. [26,45,46] Moreover, enzyme-linked immunosorbent assay (ELISA) results confirmed that the antigenicity of these BP particles was not jeopardized after incubation at different temperatures ranging from 4 °C to 56 °C for 4 weeks. [26,45,46] We additionally developed modified BPs coated with the NP366 (NT68) epitope derived from the influenza A strain A/NT/60/68 (H3N2) and the PA 224 epitope in order to utilize F5 CD8 + T cells, which are TCR transgenic CD8 + T cells specific for the influenza A virus nucleoprotein epitope from the strain A/NT/60/68 (H3N2), for in vitro and in vivo T cell proliferation studies.…”

“…[26,45,46] Moreover, enzyme-linked immunosorbent assay (ELISA) results confirmed that the antigenicity of these BP particles was not jeopardized after incubation at different temperatures ranging from 4 °C to 56 °C for 4 weeks. [26,45,46] We additionally developed modified BPs coated with the NP366 (NT68) epitope derived from the influenza A strain A/NT/60/68 (H3N2) and the PA 224 epitope in order to utilize F5 CD8 + T cells, which are TCR transgenic CD8 + T cells specific for the influenza A virus nucleoprotein epitope from the strain A/NT/60/68 (H3N2), for in vitro and in vivo T cell proliferation studies. Characterization of these particles confirmed that they were similar to the BP-NP 366 /PA 224 with regards to size, composition, and thermostability (Figures S4-S7, Supporting Information).…”

Efficiency of recombinant Ybgf in a double antigen-ELISA for the detection of Coxiella antibodies in ruminants

“…Ybgf has been found to be one of the most important immunodominant antigens in humans and laboratory animals, as well as one of the most promising candidates for future applications in serodiagnosis and vaccinology ( Bach et al, 2023 ; Jiao et al, 2014 ; Sam et al, 2023 ). This periplasmic protein is considered a specific marker of PhII (acute infection).…”