Safety and immunogenicity of recombinant Bacille Calmette-Guerin (rBCG) expressing Burrelia burgdorferi outer surface protein A (OspA) lipoprotein inadult volunteers: a candidate Lyme disease vaccine

This phase I clinical trial was designed to determine the feasibility of us ing rBCG as a live bacterial vaccine vector for the outer surface protein A (OspA) of Borrelia burgdorferi and as model for other vaccines based on a rBCG vector. To construct the vaccine, a signal peptide derived from a myco bacterial lipoprotein was used to direct the export, and membrane-associate d surface expression, of OspA in a standard strain of BCG (Connaught). The rBCG OspA vaccine was safe and immunogenic in several animal species, and p rotective in a mouse model of Lyme borreliosis. An intradermal injection (0 .1 ml) of rBCG OspA was administered to 24 healthy adult volunteers sequent ially at one of four dose levels, ranging from 2.0 x 10(4) CFU to 2 x 10(7) CFU . using a dose-escalation design. All volunteers were initially PPD-sk in taut and OspA antibody negative, and they were monitored for 2 years aft er immunization. Three volunteers had mild flu-like reactions 1-2 days afte r vaccination. Local ulceration and drainage at the site of injection, whic h occurred in 50% and 83% of volunteers in the two highest dose groups, per sisted for 1-70 days before the ulcers healed. Most of the drainage samples yielded rBCG colonies that contained the OspA plasmid. Thirteen of 24 vacc inees. principally in the two highest dose groups, converted their PPD skin tests from negative to positive. None of the 24 volunteers developed OspA antibody. In conclusion, the current rBCG vaccine construct, the first such construct tested in humans, had a safety profile comparable to that of lic ensed BCG. but it did not elicit primary humoral responses to the vectored antigen. (C) 1999 Elsevier Science Ltd. All rights reserved.