Assessment of vaccine delivery systems and their impact on the enhancement of immunogenicity, potency and safety of specific livestock vaccines used in South Africa

Abstract

Since its establishment in 1908, the Onderstepoort Veterinary complex has developed more than 50 veterinary vaccines that have been used over the period in the control of animal viral and bacterial diseases in Southern Africa and elsewhere around the world. These vaccines have been either live attenuated or inactivated. The inactivated vaccines are generally formulated with an aqueous or an oil adjuvant. Onderstepoort oil-adjuvanted vaccines have been formulated with the old Freund’s formulation, using surfactants that are not always compliant with current regulatory requirements. Other disadvantages associated with use of the traditional Freund’s formulation include safety in vaccinated animals, unavailability of certain reagents or components, as well as their impact to the cost of the final vaccine. The present study was designed to assess four oil-adjuvanted Onderstepoort vaccines, i.e. the E. coli, the enterotoxaemia or Pulpy kidney, the Vibrio or Campylobacter fetus and the Infectious coryza vaccines. The first three vaccines are formulated with a surfactant that is no longer readily available and is not registered by regulatory authorities, while the surfactant used in the Infectious coryza vaccine tends to result in adverse reactions in vaccinated chickens. The traditional liquid paraffin Marcol was compared to two new liquid paraffin white oils (PFP8 and PFP14), while the traditional emulsifiers Cirrasol EN-MP® and Arlacel® were compared to two new products, Montanide 103™ and Simulsol-P2®. In addition, Cirrasol EN-MP® was compared to Arlacel®, given the fact that the latter is an approved emulsifier for use in animal vaccines. Two ready-to-use emulsifiers, i.e. Montanide™ ISA 70 VG and Montanide™ ISA 206, were also tested with the Infectious coryza vaccine. The three liquid paraffins and four surfactants were evaluated for their physical characteristics, as well as their ability to generate a safe and effective vaccine when formulated with the above four vaccine antigens. The safety and efficacy of the different formulations were evaluated in both laboratory animals and target animals, i.e. sheep, cattle and chicken. The results obtained can be summarized as follows. (i) The two new liquid paraffins had similar physical characteristics as the traditional Marcol, and they also did not cause adverse reactions in vaccinated animals; (ii) Simulsol-P2® displayed a poor ability to form a stable emulsion for the above vaccines; (iii) Montanide 103™ was stable and was safe in most of the vaccines, but caused persistent local reactions in the E. coli vaccine; and (iv) the Arlacel® formulations were stable, safe and showed better immunogenicity profiles as compared to the other formulations.