A novel multivalent outer surface protein A (OspA)-based vaccine candidate (VLA15) against Lyme borreliosis (Lyme disease) appeared safe and generated immunogenicity in young adults, according to phase I trial results.
Among nearly 200 trial participants randomly assigned to receive a three-dose primary immunization with alum-adjuvanted or non-adjuvanted VLA15 in 12, 48, or 90-μg doses, immunogenicity was highest at day 85 with the highest dose and higher still when it was alum adjuvanted (geometric mean titre range 61.3-321.7 adjuvanted vs 23.8-111.5 U/mL non-adjuvanted at 90 μg).
Safety and tolerability were similar between adjuvanted and non-adjuvanted formulations, with adverse events reported in 94-97% of participants getting the intermediate (48 μg) and highest doses (90 μg) when compared with the lowest dose (89% with 12 μg, 95% CI 69.4-94.5). Injection site tenderness or pain were the most common adverse events; common systemic reactions were headache in 45%, excessive fatigue in 25%, and myalgia in 25%.
"This novel multivalent vaccine candidate against Lyme borreliosis was safe and immunogenic and paves the way to further clinical development," reported Susanne Eder-Lingelbach, MSc, of drug developer Valneva Austria in Vienna, and colleagues in Lancet Infectious Diseasesopens in a new tab or window.
"All VLA15 doses and formulations showed a favourable safety and tolerability profile and were immunogenic against all OspA serotypes, and a booster dose induced a substantial anamnestic immune response," they added.
The CDC reports approximately 30,000 Lyme disease cases per year in the U.S. but suggests a 10-fold higher incidence is likely, as it is highly underreported. Infection causes fever, headache, fatigue, and erythema migrans. If left untreated, the infection can spread to joints, the heart, and the nervous system.
To prevent infection, the VLA15 vaccine targets outer surface protein A (OspA), a dominant surface protein expressed by spirochetes of Borrelia spp in the tick midgut, and neutralizes the bacteria before it can infect a human.
"What makes the OspA vaccine special is that it works while the tick is feeding (which takes several days) and attacks the pathogen only inside the tick, preventing its transmission," Ondrej Hajdusek, PhD, and Jan Perner, PhD, both from the Czech Academy of Sciences in Ceske Budejovice, Czech Republic, wrote in an accompanying editorialopens in a new tab or window.
The multivalent vaccine formula targets OspA serotypes from Borrelia species from North America (B burgdorferi), and Europe (B burgdorferi, B afzelii, B garinii, and B bavariensis) and it consists of three lipidated OspA heterodimers (reflecting six Borrelia OspA serotypes) expressed in Escherichia coli.
That's a step up from the prior Lyme shot developed for humans -- the monovalent LYMErix vaccine.
While that shot was licensed and available from 1998-2002, it did not stay on the market long after being associated with autoimmune arthritis. Loss of vaccine confidence led to discontinuation by the manufacturer. Another Lyme vaccine (ImuLyme) was also developed around the same time but never licensed.
VLA15 also is different in that it doesn't contain the epitope present in the LYMErix vaccine thought to be associated with the development of autoimmune arthritis through a cross-reaction with human leukocyte function-associated antigen (hLFA1), Hajdusek and Perner wrote.
The exact mechanism of VLA15's complement-independent, antibody-mediated inhibition is not yet fully understood, the editorialists noted, but how fully the vaccine inhibits B burgdorferi in the tick's gut while it's feeding correlates closely with blood levels of the protective antibodies from the vaccine.
"If the titre of anti-OspA antibodies is insufficient at the time of tick infestation, spirochaetes can escape, enter the host's skin, and most likely cause infection. Therefore, to maintain high titres of protective antibodies, annual boosters would be required before each tick season."
In the current trial, Eder-Lingelbach and co-authors reported that the vaccine produced antibodies for all the protein OspA serotypes targeted. "The observed seroconversion rates found in the adjuvanted treatment groups 1 month after the booster vaccination ranged from 88% to 100% which is similar to published seroconversion rates of formerly licensed vaccines against Lyme borreliosis," the researchers noted.
The antibodies declined within 5 months after the booster dose given about 13 months after the start of the three-dose vaccine series. "Substantial IgG concentrations were still detected at this point in time, which represents approximately the end of a tick season," they noted, adding that "this would indicate that after a 3-dose initiation regimen, booster doses would be needed annually."
The first-in-human trial included 179 participants (65% female, 93% white) ages 18 to 39 from Europe and the U.S. between January 2017 and January 2019. All were seronegative for B burgdorferi sensu lato at baseline. Previously infected or Lyme-vaccinated individuals were excluded, as were those with autoimmune diseases, arthritis, or clinically relevant musculoskeletal disorders.
Common adverse reactions to vaccine included tenderness (84%), injection site pain (67%) headache (45%), excessive fatigue (25%), and myalgia (25%).
Researchers noted the study is limited as it did not include children or the elderly and does not include any long-term data.
VLA15 phase III trials are currently underway, and the vaccine has been given fast track designation by the FDA, with potential to be evaluated for approval in 2026.
The editorialists called the vaccine a milestone in the fight against Lyme disease, saying they "eagerly await the results of the next clinical trials."
Disclosures
The trial was sponsored by Valneva Austria.
Study co-authors reported funding from Valneva to conduct the study. Most co-authors are Valneva employees and reported owning stock and share options in Valneva.
Hajdusek and Perner had nothing to disclose.
Primary Source
Lancet Infectious Diseases
Source Reference: opens in a new tab or windowBézay N, et al "Safety and immunogenicity of a novel multivalent OspA-based vaccine candidate against Lyme borreliosis: a randomised, phase 1 study in healthy adults" Lancet Infect Dis 2023; DOI: 10.1016/S1473-3099(23)00210-4.
