Initial Evaluation of a Recombinant Clostridium botulinum A/B Vaccine (rBV A/B) in Healthy Volunteers
Author:
McKee, KT, Greenberg, RN, Swiderski W, Plummer, EA, Starner RA, Henderson, ISummary:
Background. No licensed vaccine currently exists to protect against exposure to botulinum neurotoxins (BoNTs). A recombinant BoNT vaccine, conceived by the U.S. Army Medical Research Institute of Infectious Diseases, was derived from C. botulinum neurotoxin serotypes A and B expressed from synthetic genes introduced into Pichia pastoris. rBV A/B protects against intramuscular BoNT challenge in experimental animals. Methods: Safety and immunogenicity of rBV A/B at three ascending dosage levels (5 ìg, 10 ìg, and 20 ìg of each serotype antigen adsorbed to 0.2 % (w/v) Alhydrogel™) were assessed in 33 healthy adults. Volunteers received 0.5 mL injections IM at days 0 and 28, and are being followed for 12 months. BoNT neutralizing antibody concentrations (NACs) were measured using a mouse neutralization assay.
Results. rBV A/B was well tolerated at all dosage levels. Two volunteers receiving 20 ìg doses reported moderate injection site pain one with local erythema); no other significant local or systemic adverse reactions have been observed to date. BoNT neutralizing antibodies were detectable by one week after the second injection in all dosage cohorts. By day 112, antibodies were detected in a high proportion of vaccinees receiving both 5 ìg (64% vs. Type A, 73% vs. Type B) and 10 ìg (91% vs. Type A, 82% vs. Type B) dosages. Geometric mean NACs for both serotypes showed biphasic patterns, with early peaks by days 35-42, a decrease by day 56, then subsequent spontaneous higher peaks after
that point. Data from the high dosage cohort are pending.
Conclusions. rBV A/B appears to be well tolerated and immunogenic in humans at the three dosages evaluated. Based upon information available to date, advancement of rBV A/B to Phase 2 testing for schedule selection appears warranted.
