Production, immunogenicity, stability, and safety of a vaccine against Clostridium perfringens beta toxins

Abstract

Background and Aim: The beta toxin is causing the most severe Clostridium perfringens-related diseases. This work was dedicated to developing a vaccine against beta toxin using C. perfringens type C (NCTC 3180). Materials and Methods: The crude toxoid harvest contained 710 limits of flocculation (Lf)/mL. The vaccine was formulated. Each 1 mL of the final vaccine product contained at least 50 Lf/mL of beta toxoids, 0.2 mL 3% aluminum hydroxide gel (equivalent to 5.18 mg of aluminum), <0.001% W/V thiomersal, formaldehyde <0.05% W/V, and ∼0.7 mL phosphate-buffered saline (pH 7.2). The efficacy of the vaccine was evaluated by potency, stability, and safety tests. Results: The vaccine demonstrated 24.36 IU/mL (standard deviation, ±0.56) and 14.74 IU/mL (±0.36) of neutralizing antibodies in rabbits and cattle, respectively. Indeed, these levels were above the minimum recommended by international protocols since the obtained antibody levels had 2.43- and 1.47-fold increase in both rabbits and cattle, respectively, over the minimum antitoxin level suggested by the United States Department of Agriculture. Interestingly, our formulation was capable of inducing 1.65-fold higher immune responses in rabbits than that stimulated in cattle (65% increase) with a significant difference (p<0.0001). The vaccine was stable up to 30 months. The vaccinated rabbits were suffered from a temporarily slight increase in temperatures in the first 10 h without any significant difference (p>0.05). Conclusion: The research showed a procedure for the manufacturing process of the vaccine against C. perfringens beta toxins with a feasible quantity and the vaccine described here showed to be effective in eliciting levels of neutralizing antibodies higher than required by international standards. In addition, The vaccine was stable up to 30 months. Thus, it may represent an effective and safe for preventing C. perfringens-related diseases in rabbits and cattle, although further studies to prove its efficacy in the field on other farm animals are still needed.

Immunogenicity of a newly developed vaccine against Clostridium perfringens alpha-toxin in rabbits and cattle

“…In line with the findings of this study, evidence reports a recombinant vaccine that produces 9.6 and 5.19 IU/mL neutralizing antibodies in rabbits and cattle, respectively [17,24]. Consistent with the findings of the present study, a similar previous study conducted in 2016 indicated a 1.80-fold decrease in immune response (antibody titer) in cattle than in rabbits [21,23]. In the present study, the difference between rabbits and cattle was 3.90 IU/mL, which coincides with the value reported by a previous study on alpha-toxin [21].…”

“…Initially, C. perfringens type A, as well as its respective alpha-toxin, was inactivated by the addition of formaldehyde. This is because formaldehyde -a one-carbon, highly hydrophilic aldehydecan eliminate the damaging effects, reduce bacterial replications, and detoxify bacterial toxins [22,23]. A question then emerges regarding the exact of the formulated vaccine that can elicit and maintain immune responses.…”

Evaluation of Aluminium Hydroxide Nanoparticles as an Efficient Adjuvant to Potentiate the Immune Response against Clostridium botulinum Serotypes C and D Toxoid Vaccines

“…Moreover, the potency demonstrated by nanoalum in the bivalent vaccine was maintained in the multivalent vaccine. Although experimental models do not always accurately mimic the immune responses in target animals [ 37 ], the nanoalum vaccines used in this study have the potential to meet or exceed the minimum required protective immunity in target animals. Nevertheless, further experiments in field animals are required to evaluate the extent to which the nanoalum-containing vaccines induce an immunological response.…”

Staphylococcal enterotoxin B as DNA vaccine against breast cancer in a murine model

“…Specific K m values of species are coefficient of body surface area (for a 60-kg adult human, K m = 37, for a 20-g mouse, K m = 3) (Rattan et al 2011;Saadh et al 2020).…”