Vaccination of rabbits with an alkylated toxoid rapidly elicits potent neutralizing antibodies against botulinum neurotoxin serotype B.

New Zealand White (NZW) rabbits were immunized with several different nontoxic botulinum neurotoxin serotype B (BoNT/B) preparations in an effort to optimize the production of a rapid and highly potent, effective neutralizing antibody response. The immunogens included a recombinant heavy chain (rHc) protein produced in Escherichia coli, a commercially available formaldehyde-inactivated toxoid, and an alkylated toxoid produced by urea-iodoacetamide inactivation of the purified active toxin. All three immunogens elicited an antibody response to BoNT/B, detected by enzyme-linked immunosorbent assay (ELISA) and by toxin neutralization assay, by the use of two distinct mouse toxin challenge models. The induction period and the ultimate potency of the observed immune response varied for each immunogen, and the ELISA titer was not reliably predictive of the potency of toxin neutralization. The kinetics of the BoNT/B-specific binding immune response were nearly identical for the formaldehyde toxoid and alkylated toxoid immunogens, but immunization with the alkylated toxoid generated an approximately 10-fold higher neutralization potency that endured throughout the study, and after just 49 days, each milliliter of serum was capable of neutralizing 10(7) 50% lethal doses of the toxin. Overall, the immunization of rabbits with alkylated BoNT/B toxoid appears to have induced a neutralizing immune response more rapid and more potent than the responses generated by vaccination with formaldehyde toxoid or rHc preparations.

Development of cytomegalovirus vaccines: prospects for prevention of congenital CMV infection.

Congenital cytomegalovirus (CMV) infection is an important cause of hearing, cognitive, and motor impairments that cannot be effectively prevented or treated by any current medical or public health interventions. A review of priorities for vaccine development by The Institute of Medicine of the National Academy of Sciences concluded that a vaccine to prevent congenital CMV infection should be a top priority for the United States. Evidence from clinical studies indicates that immunity to CMV can reduce the frequency and severity of disease. Laboratory investigations have identified structural and nonstructural CMV proteins that play a key role in eliciting protective immunity. The rationale for development of a CMV vaccine has been strengthened further by studies in experimental animals demonstrating the ability of immunization with subunit vaccines to prevent disease and transplacental transmission of virus. At least 4 CMV vaccines are in clinical trials, and advances in biotechnology are paving the way for additional novel vaccines.