Botulinum neurotoxin neutralizing activity of immune globulin (IG) purified from clinical volunteers vaccinated with recombinant botulinum vaccine (rBV A/B)

Autor: Ian Henderson, Nancy A. Niemuth, Karen Metcalfe, William Swiderski, Michelle L. Vassar, Jeffry D. Shearer
Rok vydání: 2010
Předmět:
Zdroj: Vaccine. 28:7313-7318
ISSN: 0264-410X
Popis: The basis for efficacy of the recombinant botulinum vaccine, serotypes A and B (rBV A/B) is that neutralizing antibodies induced by vaccination bind to botulinum neurotoxin complex serotype A, subtype A1 (BoNT/A1) and serotype B, subtype B1 (BoNT/B1) and prevent their actions at cholinergic neurons. The protective capacity of BoNT/A1 and BoNT/B1 neutralizing antibodies derived from the serum of clinical volunteers vaccinated with rBV A/B was evaluated in a guinea pig passive transfer model and a mouse bioassay. Guinea pigs passively immunized to achieve circulating neutralizing antibody concentration (NAC) levels representing the lowest measurable concentrations for BoNT/A1 and BoNT/B1 were protected against an intramuscular (IM) challenge more than 10 times the guinea pig IM median lethal dosage for BoNT/A1 and BoNT/B1. The passively immunized guinea pigs were asymptomatic during the 14-day post-challenge observation period. Control guinea pigs died within 48 h after challenge. Calculation of neutralizing efficiency of antibodies using results from a mouse bioassay indicated that a simple linearly proportional relationship does not exist between NAC level and the amount of BoNT neutralized. Based on this finding, estimates of level of protection must consider variability in BoNT neutralizing efficiency at different NAC levels. The protective capacity of human BoNT/A1 and BoNT/B1 neutralizing antibodies induced by rBV A/B vaccination was verified in a guinea pig passive immunization model. Additionally, estimates of the neutralizing efficiency have been established for BoNT/A1 and BoNT/B1 neutralizing antibodies obtained from clinical volunteers vaccinated with the rBV A/B.
Databáze: OpenAIRE