European studies of the Lyme disease vaccine co-developed by researchers at Stony Brook University, Brookhaven National Laboratory, and at Baxter International Inc., a U.S. based healthcare company, indicate tolerance and efficacy against all targeted species of Borrelia, the causative agent.
In the research published online in The Lancet Infectious Diseases, investigators led by P. Noel Barrett, PhD, of Baxter Biomedical Research Centre, and co-authors show that the vaccine generated enough antibodies against the pathogen in the phase 1/2 clinical trial sponsored by Baxter International. Borrelia causes Lyme disease in Europe and the United States. The investigators tested the safety and immunogenicity of the vaccine in a range of doses in 300 people living in Austria and Germany. They administered three primary immunizations and one booster immunization to the participants. The three vaccinations comprised 30 μg, 60 μg, or 90 μg of the surface protein antigen (OspA) with or without an adjuvant, in intervals of 28 days. A booster dose was given nine to 12 months after the first immunisation. The researchers then monitored the participants for frequency and severity of injection-site and systemic reactions within a week of each vaccination, and the antibody responses to OspA serotypes 1-6. The vaccine evoked substantial antibody response against all species of Borrelia at all doses and formulations, with or without an adjuvant, which is an additional agent that stimulates immune response to the vaccine. The 30 μg adjuvanted formulation evoked the highest antibody response after the booster dose was administered.Side effects were mild and minimal, without any related serious events in the sample population.
"The results of the clinical trial conducted by Baxter are promising because the vaccine generated a potent human immune reaction, covered the complete range of Borrelia active in the entire Northern hemisphere, and produced no major side effects," said Dr. Luft, a co-author on the paper, in a media interview. "We hope that a larger-scale, Phase 3 trial will demonstrate not only a strong immune response but true efficacy in a large population that illustrates protection against Lyme disease."
Dr. Luft said that for years, one of the main challenges of developing a Lyme disease vaccine was to discover a method that could produce a vaccine that works against all Borrelia species. In conjunction with the experts at Stony Brook and Brookhaven, Drs. Luft and Dunn focused on the predominant Borrelia outer surface protein for their vaccine development. The Borrelia species are spirochete bacteria residing in ticks, which commonly transmit the disease. Using the scaffold of the outer protein, called OspA, the investigators along with researchers at Baxter, genetically engineered a set of unique OspA proteins, which share different components from different species of Borrelia.
Benjamin Luft, MD, the Edmund D. Pellegrino Professor of Medicine at Stony Brook University School of Medicine, and the late John Dunn, Ph.D., a biologist at Brookhaven National Laboratory along with researchers at Baxter International formulated the Lyme vaccine used in the clinical trial.
While the Stony Brook University School of Medicine and Brookhaven National Laboratory, The Research Foundation of the State of New York licensed intellectual property of the Lyme vaccine technology to Baxter International, Baxter International researchers in collaboration with Luft and Dunn tweaked the technology even more to come up with the Lyme vaccine in question.
"After a series of experimentations and refinements, formulations consisting of these new OspA proteins were shown to protect against a broad spectrum of Lyme disease spirochetes," said Dr. Luft, summarizing the research results in the media interview.
"The novel multivalent OspA vaccine could be an effective intervention for prevention of Lyme borreliosis in Europe and the USA, and possibly worldwide. Larger confirmatory formulation studies will need to be done that include individuals seropositive for Borrelia burgdorferi sensu lato before placebo-controlled phase 3 efficacy studies can begin," the authors conclude.
