As Lyme disease cases increase, so does promise of a new vaccine
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Lyme disease is the most common vector-borne disease in the United States, and although cases have steadily increased — and are estimated to be significantly undercounted — there is no vaccine to prevent it.
“The prevalence of Lyme disease has been dramatically increasing, and the geography has been as well,” Paul G. Auwaerter, MD, MBA, clinical director of the division of infectious diseases and professor of medicine at Johns Hopkins Medicine, told Healio | Infectious Disease News.
“It used to be quite a New England, upper Mid-Atlantic and upper Midwest disease, but now it is typically found through the whole state of Pennsylvania, Ohio, Michigan, Virginia. States that were not reporting significant amounts of Lyme disease years ago, now are,” he said.
A Lyme disease vaccine, LYMERix, was available in the U.S. for about 3 years before GSK pulled it from the market in 2002 after reports of side effects — later proven inaccurate — and other issues tanked its sales. The vaccine was only tested and approved for people aged 15 to 70 years, excluding young children, a high-risk group.
According to Auwaerter, drug companies were hesitant for years to wade back into Lyme vaccine development, but as the disease has become endemic over a wider swath of the country, they have been lured back.
In the only late-stage project, Pfizer and Valneva are conducting an ongoing phase 3 clinical trial for VLA15, a Lyme disease vaccine candidate aimed at protecting against the six most dominant serotypes of Borrelia burgdorferi that circulate in the U.S. and Europe, where vaccine trials are also being conducted.
“The situation now is different than it was 20 years ago,” Paul S. Mead, MD, MPH, chief of the CDC’s Bacterial Diseases Branch in Fort Collins, Colorado, told Healio | Infectious Disease News. “Lyme disease cases and populations at risk have increased substantially, and we have 2 decades of evidence that other prevention methods, such as education and tick removal, are not adequate by themselves.”
‘Cases have continued to climb’
Tick-borne diseases make up roughly 90% of reported vector-borne diseases. Eight out of 10 cases are Lyme disease, which is spread by Ixodes scapularis — the blacklegged, or deer, tick.
U.S. national strategy calls for reducing the number of laboratory-confirmed Lyme disease cases by 25% by 2035, compared with 2022. HHS launched a national plan in February 2024 to reduce the incidence of vector-borne diseases spread by mosquitoes, fleas, ticks and lice in the U.S., which has doubled in the last 2 decades. The National Public Health Strategy to Prevent and Control Vector-Borne Diseases was in development since 2019, when the Kay Hagan Tick Act was signed into law, mandating a national plan.
There are limitations to Lyme disease surveillance in the U.S. Like other nationally notifiable diseases, cases are underreported and misclassified, according to the CDC.
In 2022, the CDC revised the case definition of Lyme disease for the fifth time since it was first implemented in 1991. The change resulted in the number of reported cases in 2022 being nearly double the annual average from 2017 to 2019 — 62,551 cases vs. 37,118 cases, respectively, according to findings published in MMWR this past February by Kiersten J. Kugeler, PhD, and colleagues from the CDC’s Division of Vector-Borne Diseases.
In actuality, nearly 500,000 people in the U.S. are thought to be diagnosed with and treated for Lyme disease each year, including people who are treated based on clinical suspicion of Lyme disease but do not actually have it, according to the results of an analysis published in 2021.
Before the recent tweak to the case definition, Lyme disease surveillance required the collection of clinical information coupled with laboratory evidence of infection, according to Kugeler and colleagues. With the new definition, laboratory evidence alone was justified as enough information, without additional clinical confirmation.
In a previous interview, Auwaerter likened comparing the mean case number from one year to multiple years when the definition was different to comparing an apple to a pear; they are fruits, but they are not the same.
“Despite substantial efforts directed at education and tick control, cases have continued to climb,” Mead said. “It is clear that we need new tools to prevent and control this important disease to keep people safe.”
Initial problems with Lyme disease vaccination
There are reasons to vaccinate against Lyme disease besides preventing the acute infection, according to Eugene D. Shapiro, MD, professor of pediatrics and epidemiology at Yale School of Medicine. Another potential public health impact of vaccination is the prevention of legitimate post-Lyme disease syndromes.
“The public health impact of Lyme disease is beyond just Lyme disease itself — there are a lot of post-Lyme syndromes, some legitimate and some not,” Shapiro told Healio | Infectious Disease News.
The FDA approved LYMErix in 1998 based on trial results showing that it reduced risk for infection by nearly 80%. The vaccine required three doses, the last two given 1 month and 12 months after the first.
According to a review of LYMErix that was published in Epidemiology & Infection in 2007, there were other issues with the vaccine. Safety and efficacy data in children were limited, and the vaccine only protected against the predominant serotype of B. burgdorferi in North America, not other Borrelia strains that circulate overseas.
There also were concerns that vaccination might cause people to worry less about potential exposure to ticks.
Although the vaccine was approved by the FDA, the CDC’s Advisory Committee on Immunization Practices (ACIP) stopped short of issuing a strong recommendation for its use, saying that it “should be considered” for people aged 15 to 70 years who are frequently exposed to ticks and “may be considered” for people exposed to ticks, but less frequently and for less time. It did not recommend vaccination for people with minimal or no exposure to ticks.
The ACIP “issued only a permissive recommendation, largely because only a small segment of the population would benefit and, relatedly, because the vaccine was not available for children,” Courtney Gidengil, MD, MPH, a senior physician policy researcher at the Rand Corporation, and colleagues wrote in a study that analyzed survey data on potential Lyme disease vaccine uptake.
There were also concerns about the safety of the vaccine, as well as a series of lawsuits that were later settled, Shapiro said, after one of the antigens in LYMErix was thought to be causing arthritis. Although GSK removed the ingredient, and later studies suggested the vaccine was not at fault for the widely publicized side effect, the negative attention caused demand to crash.
As a result, GSK pulled the vaccine from the market and there has not been an available Lyme disease vaccine since.
‘Heightened awareness’
Although vaccine hesitancy has increased in recent years, there is evidence that people would be interested in a Lyme disease vaccine should VLA15 or another shot be licensed in the next several years.
Gidengil and colleagues surveyed more than 1,300 parents of children aged 5 to 18 years in states where Lyme disease is common or emerging and found that 68% would get their child vaccinated against it, including more than 70% in states with a high incidence of Lyme, according to results published in Vaccine in March. One-third of respondents in high-incidence areas who responded negatively to the survey said they would change their mind if the vaccine was recommended by a provider.
“Recommendations from a health care provider will likely be very important for vaccine acceptance by patients,” Mead said.
Survey responses showed that parents preferred the idea of a Lyme disease monoclonal antibody (mAb) to a vaccine, indicating that access to both could increase protection, Gidengil and colleagues said.
A 2022 survey of more than 3,300 residents of Connecticut, Maryland, Minnesota and New York showed that 64% were open to getting a Lyme disease vaccine.
“I think the differences this time are that, unlike the late 1990s and early 2000s, there’s a heightened awareness of Lyme disease,” Auwaerter said.
Mead said closely monitoring vaccine safety will be essential to assuring public confidence in a Lyme disease vaccine. According to Auwaerter, it will also be important to have a robust marketing and education campaign to show people the vaccine is safe, effective and useful, considering the history of LYMErix.
“There’s a lot of interest in ways to help prevent Lyme disease because the consequences — such as long-term complications like post-treatment Lyme disease syndrome — and now a greater recognition among the public,” Auwaerter said.
‘Abundant interest’ in vaccination
Pfizer and Valneva began recruiting participants for the phase 3 VALOR trial of VLA15 in August 2022, enrolling about 6,000 participants aged 5 years and older at up to 50 sites in North America and Europe where Lyme disease is endemic.
“We had abundant interest and had to turn people away,” said Auwaerter, who is a primary investigator on the trial at Johns Hopkins.
The trial hit a snag when Pfizer had to remove around half of the participants after identifying Good Clinical Practice violations at trial sites in the U.S. run by a third party, the company told investors in May 2023.
VALOR was fully enrolled by December 2023 with 9,437 participants, according to Pfizer and Valneva, but the delay pushed the regulatory timeline back by a year. The trial is expected to conclude by the end of 2025, and Pfizer and Valneva have said they expect to submit regulatory filings to the FDA for VLA15 sometime in early 2026 for U.S. approval, in addition to submitting data for approval in Europe at the same time.
In previously announced phase 2 trial results, the companies reported that the vaccine demonstrated strong immunogenicity with acceptable safety and tolerability profiles. Data showed that antibody levels declined over time in both children and adults but remained above baseline 6 month after the completion of a three-dose series of the vaccine.
Prevention recommendations
In the absence of a vaccine, preventing Lyme disease comes down to preventing tick bites.
Potential exposure to ticks is most likely to happen during warmer months, but in its recommendations for preventing tick bites and Lyme disease, the CDC notes that tick exposure is possible year-round.
Most tick bites, according to Auwaerter, are likely to happen near people’s houses — in back yards, near brushy or wooded areas — as well as when camping or in wilderness areas.
The CDC recommends that, before potential exposure to ticks, people treat their clothing and gear with products containing 0.5% permethrin. Clothing and gear treated with permethrin are also available.
On top of this, while in wooded and brushy environments, the agency suggests avoiding areas with high grass and leaf litter, as well as walking in the center of trails if possible.
After potential tick exposure, the CDC recommends that people check their clothing for ticks, wash their clothing, examine gear and pets, shower and check their body for ticks.
In February, Tarsus announced positive findings from a randomized, double-blind, placebo-controlled phase 2 trial of TP-05, an oral formulation of the antiparasitic lotilaner that people can take to kills ticks attached to their body, preventing them from transmitting the bacterium, which usually takes 36 to 48 hours.
The trial evaluated tick mortality within 24 hours of attachment and showed that TP-05 was 97% effective with a high dose and 92% effective with a low dose compared with 5% among participants who received placebo, according to Tarsus. Tick mortality was also high at 30 days after a dose of TP-05.
Mead said additional preventives under development include a messenger RNA vaccine candidate and mAbs.
References:
- CDC. Lyme disease surveillance and data. https://www.cdc.gov/lyme/data-research/facts-stats/index.html. Accessed April 24, 2024.
- CDC. Ticks: Preventing tick bites. https://www.cdc.gov/ticks/prevention/index.html. Accessed May 8, 2024.
- CDC. National public health strategy to prevent and control vector-borne diseases in people. https://www.cdc.gov/vector-borne-diseases/php/data-research/national-strategy/index.html. Accessed May 23, 2024.
- CDC. NNSSS: Lyme disease (Borrelia burgdorferi) 2022 case definition. https://ndc.services.cdc.gov/case-definitions/lyme-disease-2022/. Last reviewed Aug. 30, 2021. Accessed May 8, 2024.
- Gidengil C, et al. Vaccine. 2024;doi:10.1016/j.vaccine.2024.01.081.
- HHS. The Kay Hagan Tick Act. https://www.hhs.gov/ash/osm/innovationx/vector-borne-disease-national-strategy/kay-hagan-tick-act/index.html. Last reviewed Aug. 27, 2023. Accessed May 28, 2024.
- HHS. Vector-borne disease national strategy. Last reviewed Feb. 6, 2024. Accessed May 8, 2024. https://www.hhs.gov/ash/osm/innovationx/vector-borne-disease-national-strategy/index.html.
- Hook SA, et al. Vaccine. 2022;doi:10.1016/j.vaccine.2021.11.065.
- Kugeler KJ, et al. MMWR Morb Mortal Wkly Rep. 2024:doi:10.15585/mmwr.mm7306a1.
- Modlin JF, et al. MMWR Recomm Rep. 1999; 48(RR07);1-17, 21-5.
- Nigrovic LE, et al. Epidemiol Infect. 2007;doi:10.1017/S0950268806007096.
- Pfizer and Valneva complete recruitment for phase 3 VALOR trial for Lyme disease vaccine candidate, VLA15. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-valneva-complete-recruitment-phase-3-valor-trial. Published Dec. 4, 2023. Accessed April 24, 2024.
- Tarsus announces positive topline results from Carpo, a phase 2a proof-of-concept “tick-kill” trial evaluating tp-05 (lotilaner) for the prevention of Lyme disease. https://ir.tarsusrx.com/news-releases/news-release-details/tarsus-announces-positive-topline-results-carpo-phase-2a-proof. Published Feb. 22, 2024. Accessed May 8, 2024.
- Valneva and Pfizer report 6-month antibody persistence data in children and adults for Lyme disease vaccine candidate. Published Dec. 1, 2022. Accessed May 28, 2024.
- Valneva reports first quarter 2023 financial results and provides corporate updates. https://valneva.com/press-release/valneva-reports-first-quarter-2023-financial-results-and-provides-corporate-updates/. Published May 4, 2023. Accessed May 23, 2024.
For more information:
Paul G. Auwaerter, MD, MBA, can be reached at pauwaert@jhmi.edu.
Paul S. Mead, MD, MPH, can be reached at media@cdc.gov.
Eugene D. Shapiro, MD, can be reached at eugene.shapiro@yale.edu.
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