Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218.

We conducted a phase II, randomized, double-blind, placebo-controlled, safety and immunogenicity study of a serially passaged, plaque-purified live chikungunya (CHIK) vaccine in 73 healthy adult volunteers. Fifty-nine volunteers were immunized one time subcutaneously with the CHIK vaccine and 14 were immunized with placebo (tissue culture fluid). Vaccinees were clinically evaluated intensively for one month, and had repeated blood draws for serological assays (50% plaque-reduction neutralization test) for one year. Except for transient arthralgia in five CHIK vaccinees, the number and severity of local and systemic reactions and abnormal laboratory tests after immunization were similar in CHIK vaccinees and placebo recipients. Fifty-seven (98%) of 58 evaluable CHIK vaccinees developed CHIK neutralizing antibody by day 28, and 85% of vaccinees remained seropositive at one year after immunization. No placebo recipients seroconverted. This promising live vaccine was safe, produced well-tolerated side effects, and was highly immunogenic.

Safety and immunogenicity of recombinant Bacille Calmette-Guérin (rBCG) expressing Borrelia burgdorferi outer surface protein A (OspA) lipoprotein in adult volunteers: a candidate Lyme disease vaccine.

This phase I clinical trial was designed to determine the feasibility of using 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 mycobacterial lipoprotein was used to direct the export, and membrane-associated surface expression, of OspA in a standard strain of BCG (Connaught). The rBCG OspA vaccine was safe and immunogenic in several animal species, and protective in a mouse model of Lyme borreliosis. An intradermal injection (0.1 ml) of rBCG OspA was administered to 24 healthy adult volunteers sequentially 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-skin test and OspA antibody negative, and they were monitored for 2 years after immunization. Three volunteers had mild flu-like reactions 1-2 days after vaccination. Local ulceration and drainage at the site of injection, which occurred in 50% and 83% of volunteers in the two highest dose groups, persisted for 1-70 days before the ulcers healed. Most of the drainage samples yielded rBCG colonies that contained the OspA plasmid. Thirteen of 24 vaccinees, 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 licensed BCG, but it did not elicit primary humoral responses to the vectored antigen.

Results of screening a large group of intercollegiate competitive athletes for cardiovascular disease.

To determine the feasibility of detecting cardiovascular disease in a large group of young competitive athletes, a prospective screening evaluation of intercollegiate student athletes was undertaken at the University of Maryland. Initial clinical screening (including personal and family history, physical examination and 12 lead electrocardiogram) was performed in 501 athletes. Ninety of these subjects had positive findings on one or more of the three studies and agreed to further cardiologic evaluation. The vast majority (75 [84%] of 90) had no definitive evidence of cardiovascular disease, although 1 athlete had mild systemic hypertension and 14 (15%) had echocardiographic evidence of relatively mild mitral valve prolapse that had not been previously suspected. In three athletes with relatively mild ventricular septal hypertrophy (14 to 15 mm), it was not possible to discern with absolute certainty whether the wall thickening was a manifestation of hypertrophic cardiomyopathy or secondary to athletic conditioning ("athlete heart"). Therefore, this screening protocol identified no athletes with definite evidence of hypertrophic cardiomyopathy, Marfan's syndrome or other cardiovascular diseases that convey a significant potential risk for sudden death or disease progression during athletic activity. This failure to identify such diseases could have been due to a lack of sensitivity of the screening tests or to the low frequency with which these diseases occur in youthful healthy athletes. A systematic preparticipation screening program (such as the present one) does not appear to be an efficient means of detecting clinically important cardiovascular disease in young athletes.