Adjuvant Effect of Whole-Cell Pertussis Component on Tetanus Toxoid Potency in Murine Model

Abstract

There is currently an increasing interest in the development of new-generation purified antigen-based vaccines with a higher safety profile compared to conventional inactivated vaccines. The main problem of subunit vaccines is their lower immunogenicity compared to whole-cell vaccines and inducing weaker and shorter-lasting immune responses. In this paper, the results of the assay of the potency of the tetanus component combined with the diphtheria component and whole-cell pertussis vaccine (DTwP), diphtheria and tetanus vaccine (DT), and in monovalent tetanus vaccine (T) are presented. In the mice model, an adjuvant impact of the whole-cell pertussis component on the immune response against tetanus was observed. It was noticed that the potency of tetanus component in the DTwP vaccine was significantly higher than tetanus potency in DT and T vaccines, despite the same bounding ability unit of the tetanus toxoid in the vaccine formulations. The levels of induction of tetanus antibodies by the tested vaccines were also examined. There were no differences in the induction of humoral responses against tetanus by tested vaccines. This publication discusses the possible mechanisms of impact of the whole-cell pertussis component on the other vaccine antigens and the positive and negative aspects of using the whole-cell pertussis component as an adjuvant.

Keywords: adjuvant; control laboratory; diphtheria; pertussis; tetanus; vaccines.

Figure 1

Shewart’s control chart of the lower confidence limit of tetanus potency results in T vaccines. Results are shown as mean (IU/0.5 mL) plus SD.

Figure 2

Shewart’s control chart of the lower confidence limit of tetanus potency results in DT vaccines. Results are shown as mean (IU/0.5 mL) plus SD.

Figure 3

Shewart’s control chart of the lower confidence limit of tetanus potency results in DTP vaccines. Results are shown as mean (IU/0.5 mL) plus SD.

Figure 4

Statistical analysis. Challenge test in mice. Results (dots) are shown as the lower confidence limit (IU/0.5 mL) for each tested vaccine. The rectangles represent the means and ranges of results for each tested group. Statistically significant differences between T and DTP and DT and DTP groups were found (p < 0.001). No statistically significant difference between T and DT groups was found. In our study, the antibody response after immunization with monovalent and combined T vaccines was evaluated. Using the ELISA method, we demonstrated that IgG anti-TT were induced by all vaccines used in the study at the same levels—for the T vaccine, GMT of the anti-TT antibodies were at the level 18.82 µg/mL, for the DT vaccine, GMT of the anti-TT antibodies were at the level 18.75 µg/mL, and for the DTP vaccine, GMT of the anti-TT antibodies were at the level 18.62 µg/mL (Figure 5). All vaccinated mice responded to immunization against tetanus. No statistically significant differences were observed (p > 0.9). A statistical analysis showing no significant differences between the groups is presented below. Descriptive statistics of results are presented in Table 3 and Figure 6.

Figure 5

The levels of anti-TT antibody after immunization with monovalent and combined T vaccines.

Figure 6

Statistical analysis. Assessment of anti-TT IgG levels in mouse sera. Results (dots) are shown as the anti-TT level (µg/mL) for each vaccinated mouse. The rectangles represent the means and ranges of results for each tested group. No statistically significant differences between T, DT, and DTP groups were found (p > 0.9).