In a recent study published in The Lancet Infectious Diseases, researchers determine the safety and immunogenicity of a novel candidate vaccine against Lyme borreliosis.
Study: Safety and immunogenicity of a novel multivalent OspA-based vaccine candidate against Lyme borreliosis: a randomised, phase 1 study in healthy adults. Image Credit: Evgeniyqw / Shutterstock.com
What is Lyme disease?
Lyme borreliosis is a tick-borne disease that commonly occurs in North America and Europe. Every year, Lyme borreliosis affects over 200,000 and 500,000 people in Europe and the United States, respectively.
Lyme disease is caused by the pathogenic spirochetes belonging to the Borrelia burgdorferi sensu lato complex. This species comprises B. burgdorferi sensu stricto, which is responsible for serotype 1, B. garinii, which causes serotypes 3, 5, and 6, as well as B. afzelii and B. bavariensis, which cause serotypes 2 and 4, respectively.
Lyme borreliosis manifests as erythema migrans, which is an erythematous skin lesion with incidence specific to serotypes, along with fever, fatigue, headaches, myalgia or arthralgia, and mild stiffness in the neck.
Although this disease can be easily treated with antibiotics if detected in the early stages, untreated Lyme borreliosis can affect the joints and heart leading to oligoarticular arthritis and carditis, respectively. Neurological consequences of untreated Lyme borreliosis include facial palsy, meningitis, and radiculopathy.
The distribution of previous monovalent Lyme borreliosis vaccines was discontinued in the U.S. due to low acceptance after concerns about potential autoimmune arthritis induction following vaccination; however, no evidence was found for this safety concern.
About the study
In the present study, researchers evaluate the immunogenicity and safety of a hexavalent candidate vaccine VLA15 among humans after the vaccine was shown to induce long-lasting immunity in mice models.
The target of most Lyme borreliosis vaccines has been the outer surface protein A (OspA), which is dominantly expressed by the Borrelia spirochetes in the midgut of the tick vector. The antibodies induced by vaccines against Borrelia OspA are expected to target and neutralize the spirochetes in the tick midgut before they can cause infections in humans.
The hexavalent VLA15 vaccine contains three lipidated fusion proteins, each of which link the OspA C-terminal domains of two serotypes to ultimately target six serotypes.
All study participants were healthy adults between the ages of 18 and 40, whose seronegativity for Lyme borreliosis was confirmed using enzyme-linked immunosorbent assay (ELISA). The participants were randomly assigned to groups that received 12, 48, or 90 micrograms (µg) doses of the vaccine, with and without adjuvants.
The primary objective of the study was to observe safety endpoints, which included the severity and frequency of solicited systemic and local adverse reactions, as well as unsolicited mild to severe adverse reactions for up to one month after completion of the primary vaccination regimen.
The solicited local adverse reactions included pain, erythema, swelling, tenderness, itching, and induration in the injection site. Systemic reactions included fever, nausea, headache, fatigue, rash, arthralgia, flu-like symptoms, and myalgia for one week after administration of the vaccine.
The secondary endpoints included evaluating adverse events at various time points after the completiong of the primary vaccination regimen for up to one year, with additional observations conducted one and six months after booster vaccination. Vaccine immunogenicity was evaluated based on the geometric mean titers of immunoglobulin G (IgG) against any of the six serotypes, which were measured through seroconversion rates and ELISA.
A safe and effective vaccine against Lyme disease
Primary vaccination, which involved three doses of the hexavalent VLA15 vaccine against Lyme borreliosis, was safe and well-tolerated by the healthy adult human population in the study. VLA15 also elicited significant immune responses against all six serotypes based on OspA.
Some mild systemic and local adverse reactions such as tenderness and pain in the injection site, as well as myalgia, fatigue, and headache, were observed. However, no adverse reactions similar to manifestations of Lyme borreliosis, or any evidence of systemic inflammation, including changes in biomarkers such as C-reactive protein, leukocytes, or erythrocyte sedimentation rates, were observed.
Booster vaccination 13 months following the first vaccine dose was equally safe and induced substantial anamnestic immune responses. The observed reactions to the VLA15 vaccine were typical of the adverse reactions to other lipid-formulated recombination vaccines.
The hexavalent VLA15 vaccine against Lyme borreliosis was found to be safe and did not induce any serious systemic or local adverse reactions. The vaccine also elicited significant antibody responses against all six serotypes targeted by the vaccine. Furthermore, substantial anamnestic immune responses were induced by booster vaccination approximately one year after the primary vaccine.