A new Lyme disease vaccine for humans is getting closer, following the publication of research indicating the safety and efficacy of a novel multivalent OspA vaccine in people previously affected by Lyme disease. The research involved people who had previously been infected with Lyme disease bacteria, including those who were symptomatic or asymptomatic.
Unlike with some infectious illnesses, a person who has had Lyme disease previously remains vulnerable to infection in the future.
Writing in the journal Clinical and Vaccine Immunology, Wressnigg and colleagues detailed results of their randomized, double-blind, phase I/II trial looking at a novel multivalent OspA vaccine in healthy adults who were either seronegative or seropositive for previous Borrelia burgdorferi sensu lato (Lyme disease) infection.
What is OspA?
OspA stands for outer surface protein-A, a protein which covers the exterior of the Borrelia bacteria and which provides a target for antibodies (immune system cells) which seek to destroy any invading Lyme disease bacteria. Previous research has indicated that vaccines based on OspA can be effective in animals, including humans, but that the variety of Borrelia subspecies necessitates a heterogenous OspA vaccine. Otherwise, a vaccine using OspA from Borrelia afzelii, for example, would not help protect someone from contracting Lyme disease from Borrelia garinii, nor from Borrelia burgdorferi sensu stricto. Thus, researchers have been working on devising an immunisation protocol to protect against a range of Borrelia subspecies.
Multivalent Lyme Disease Vaccine Success
In this latest research, participants received three, monthly, priming immunisations using either a 30 microgram or 60 microgram alum-adjuvanted OspA antigen, with a booster vaccination either 6 months or 9-12 months after the first immunisation. An alum-adjuvant is commonly used with vaccines to prompt an immune system response.
After the first immunisation, substantial ELISA and surface-binding antibody responses were found to all six OspA antigens. These were substantially increased by either booster schedule. In those who had tested seronegative to Lyme disease bacteria before the trial, antibody responses were similar with the higher or lower dose. However, in the seropositive participants, the higher dose had a more significant effect than the lower dose.
Adverse Lyme Disease Vaccine Reactions
Adverse reactions to the vaccine were largely mild and transient, and were similar in both the seronegative and seropositive participants. Thus, these results suggest that this novel multivalent Ospa vaccine for Lyme disease is well tolerated and effective (immunogenic) in people previously infected with Lyme disease bacteria.
Success with Lyme Vaccine in Healthy Adults
An earlier study by Wressnigg and colleagues, published in the Lancet Infectious Diseases in summer last year, offered an early indication of the safety and immunogenicity of adjuvanted and non-adjuvanted vaccines in healthy adults who were seronegative for B. burgdorferi. The vaccine contained protective epitopes from Borrelia species outer surface protein A (OspA) serotypes.
This double-blind, randomised, dose-escalation phase 1/2 study took place at four sites in Austria and Germany and involved 300 adults aged 18-70 years who were randomly assigned to one of six study groups. The participants received three vaccinations containing 30mcg, 60mcg, or 90mcg OspA antigen with or without an adjuvant. The vaccinations were given at 28-day intervals, with a booster 9-12 months after the first immunisation.
This study was more concerned with safety, looking specifically at the frequency and severity of adverse reactions at the injection site and body-wide. They also looked at the antibody responses to each OspA sertoype using ELISA. No serious adverse reactions were reported. The relative risk of systemic reactions was 0.54 with adjuvanted vaccinations compared to non-adjuvanted vaccinations, and this significantly lower risk was also the case for moderate or severe systemic reactions (RR 0.35).
Lower Dose Lyme Disease Vaccine Better in Healty Adults
The lower dose 30mcg formula was best tolerated, with the only adverse reactions affecting over 6% of this group including headache (in 5 participants / 10% of this group), pain at the injection site (16 /32%), and tenderness (17 /4%). The 30mcg adjuvanted formulation also led to the highest antibody titres after the booster. This is in contrast to the more recent trial where adults who had previously been infected with Lyme disease bacteria were found to have higher antibody titres with the higher 60mcg vaccinations.
These trials were funded by Baxter and the next phase in the development of a marketable Lyme disease vaccine will be placebo-controlled phase 3 efficacy studies. The results so far certainly suggest that Baxter will soon be brining a Lyme disease vaccine to market in Europe, if not in North America.
Wressnigg N, Pöllabauer EM, Aichinger G, Portsmouth D, Löw-Baselli A, Fritsch S, Livey I, Crowe BA, Schwendinger M, Brühl P, Pilz A, Dvorak T, Singer J, Firth C, Luft B, Schmitt B, Zeitlinger M, Müller M, Kollaritsch H, Paulke-Korinek M, Esen M, Kremsner PG, Ehrlich HJ, Barrett PN. Safety and immunogenicity of a novel multivalent OspA vaccine against Lyme borreliosis in healthy adults: a double-blind, randomised, dose-escalation phase 1/2 trial. Lancet Infect Dis. 2013 Aug;13(8):680-9.
Wressnigg N, Barrett PN, Pöllabauer EM, O’Rourke M, Portsmouth D, Schwendinger MG, Crowe BA, Livey I, Dvorak T, Schmitt B, Zeitlinger M, Kollaritsch H, Esen M, Kremsner PG, Jelinek T, Aschoff R, Weisser R, Naudts IF, Aichinger G. A Novel Multivalent OspA Vaccine against Lyme Borreliosis is Safe and Immunogenic in an Adult Population Previously Infected with Borrelia burgdorferi sensu lato. Clin Vaccine Immunol. 2014 Sep 3. pii: CVI.00406-14. [Epub ahead of print]