The U.S. National Institutes of Health (NIH) has provided the University of Maryland with a $3.5 million dollar grant to develop a vaccine for Lyme disease.1 Principal investigators Utal Pal, PhD, professor at the Virginia-Maryland College of Veterinary Medicine at the University of Maryland College of Agriculture and Natural Resources and Matthias Schnell, PhD, director of Thomas Jefferson University’s Jefferson Vaccine Center will collaborate on development of the novel Lyme vaccine.
Dr. Pal has identified Lyme vaccine candidate proteins and the rabies vaccine will be used as a delivery platform, although the rabies vaccine has never before been used as a vehicle for a tick born infection vaccine.2 The testing will combine the four candidate proteins Dr. Pal identified as vaccine candidates and three types of rabies vaccine platforms. According to Dr. Pal;
The best adjuvants aren’t safe for humans, but the use of a virus platform eliminates the need for an adjuvant. We are using the virus’ ability to produce a strong immune response to supply the Borrelia proteins and produce the appropriate antibodies.3
The novel research will look at targeting Borrelia proteins, BB0405 and BB139 as well as two parts of tick proteins which deliver the bacteria from tick to human. The plan is to test the best candidates on mice in the future.4
A Yearly “Antibody” Shot for Lyme Disease in the Works
There are researchers at other universities developing alternative ways to prevent Lyme disease. In an attempt to thwart Lyme disease prophylactically without using a traditional type of vaccine, researchers at University of Massachusetts Medical School Mass Biologics are working on an antibody shot called LymePrEP that would delivery an anti-Lyme antibody to the recipient. Unlike a vaccine that triggers the immune system to make antibodies, LymePrep would use a human antibody to kill the bacteria in the tick before it invaded a human host.5
The shot would use pre-exposure prophylaxis to prevent Borellia Burgdorfei, the bacteria that causes Lyme disease, from taking hold in the recipient after a tick bite. It would need to be given on a yearly basis as initial testing in mice showed efficacy lasting for only for several weeks.6 7 Phase 1 clinical trials on people who have not been exposed to Lyme disease are scheduled to be completed in 2022.8
VLA-15 Lyme Vaccine Completes Phase 2 Trials
VLA-15, another potential candidate for a Lyme disease vaccine is currently in phase 2 trials. The vaccine is being developed and marketed by pharmaceutical companies Valneva SE of France and Pfizer, Inc. of New York City, New York.9
VLA-15 vaccine targets OspA, the outer surface and most dominant protein expressed by Borrelia bacteria and is the only current vaccine for Lyme disease in clinical development.10 In July 2017, the U.S. Food and Drug Administration (FDA) granted the VLA-15 Lyme vaccine Fast Track designation.11 Vaccine manufactures that receive a fast track designation may submit less data to the FDA prior to licensing and can conduct clinical studies after the vaccine is licensed and marketed.12
Fast Track designation is granted by the FDA to products that are under development for serious conditions and have the potential to fulfill an unmet medical need. It is designed to facilitate the clinical development and expedite the review of new drugs and vaccines with the intention to accelerate the availability of promising products on the market.13
The initial Phase 2 study included 572 healthy adults ages 18-65. After the safety data was reviewed by an independent data safety monitoring board and declared positive, the main phase study commenced. In the main phase study, 180 subjects received a lower dose(135 µg) and 180 subjects received a higher dose (180 µg) of the vaccine with an aluminum adjuvant in three shots on days one, 29 and 57, while 90 subjects received a placebo.14
There were no serious adverse events reported.15 In October 2020, Valneva released initial results from its second phase II study claiming that,
the shot was generally safe across all doses and age groups tested, with the tolerability profile including fever rates being comparable to other lapidated recombinant vaccines or lipid containing formulations.16
Immunogenicity was measured by determining IgG antibodies against each of the six most prevalent OspA serotypes of Lyme bacteria covered in the vaccine. The endpoint readout was determined one month after the last shot, on day 85.17
Immune response was also assessed by looking at the Bactericidal Assay (SBA), which showed a functional immune response against all OspA serotypes.18
The higher doses used in Phase 2 invoked a higher antibody response than the lower doses used in phase 1 of the trials.19 Seroconversion rates were 81.5 to 95.8 percent in individuals receiving the highest doses.20 Looking at the same age group used in Phase 1 of the trials (18-49), the seroconversion rate was 85.6-97 percent.21
Prior exposure to Lyme disease didn’t appear to alter the immunogenicity or safety of the vaccine as seen in both phases of the trials.22
Global Market for a Lyme Vaccine Estimated at Just Under 100 Million Dollars a Year
The global market for a Lyme disease vaccine is estimated at approximately 700 to 800 million euros or 840 to 950 million US dollars annually.23
According to the agreement between Valneva and Pfizer for development and manufacturing of the VLA-15 Lyme vaccine, Valneva could receive a total of $308 million cash payments including $130 million paid upfront, $35 million in development milestones and $143 million in early commercialization milestones. Valneva is responsible for 30 percent of all development costs during the development program and will receive tiered royalties starting at 19 percent from Pfizer, which will be in charge of the late-stage development and be in complete control of commercialization of the vaccine.24
VLA-15 Lyme vaccine is intended to be used in children and adults. While the vaccine candidate has not yet been tested on children, trials are planned for children ages five years of age and above and may eventually include children even younger than five.25
The Murky History of a Lyme Disease Vaccine
Many are skeptical about the development of another vaccine for Lyme disease. VLA-15 vaccine targets OspA, similar to the last Lyme disease vaccine, LYMErix,26 which was reported to cause adverse reactions such as symptoms of Lyme disease, permanent damage to the brain and immune system and treatment resistant autoimmune arthritis.27
According to Medalerts, there were 2,225 adverse events reported to the federal Vaccine Adverse Events Reporting System (VAERS) with 460 of those events considered serious and 49 life threatening after receipt of the LYMErix vaccine.28
The true number of people who suffered serious adverse events following receipt of LYMErix vaccine is likely much higher. In a 2011 report to the U.S. Department of Health and Human Services (HHS), Harvard Pilgrim Healthcare found that less than one percent of all adverse events after receipt of any type of vaccine were reported to VAERS.29
Genetic Predisposition to LYMErix Vaccine Reactions
LYMErix was approved by the FDA in December 1998 and was withdrawn from the market approximately three years later in February 2002.30 In 1999, a study which included one of the lead researchers of the LYMErix vaccine found that OspA which was the base of the LYMErix vaccine could cross-react with a human protein in approximately 20-30 percent of the population who are positive for the HLA-DR4 gene causing complex autoimmune reactions.31 32
Patricia Smith, president of the Lyme Disease Association stated,
We don’t feel that there has been enough research done to answer the questions as to what occurred with the prior vaccine. The vaccine that is now in development is something with the same base. There were a lot of patients that thought they were harmed from that vaccine. It’s very problematic.”33
Despite the cautionary tale of the previous Lyme vaccine associated with severe reactions and long term damage, the search for a Lyme disease vaccine continues.
1 NIH funds development of novel Lyme disease vaccine. JAVMAnews. Oct. 28, 2020.
3 Veterinary college receives $3.5 million NIH grant to develop Lyme disease vaccine. Virginia Tech Daily Sept. 21, 2020.
5 Klempner M. A Lyme Disease Vaccine Doesn’t Exist, but a Yearly Antibody Shot Shows Promise. The National Interest June 7, 2020.
6 Hsu M. Stopping lyme disease before it starts. Promising new research based on pre-exposure prophylaxis, or prep. Global Lyme Alliance.
7 Klempner M. A Lyme Disease Vaccine Doesn’t Exist, but a Yearly Antibody Shot Shows Promise. The National Interest June 7, 2020.
9 Valneva and Pfizer Announce Collaboration to Co-Develop and Commercialize Lyme Disease Vaccine, VLA15. Global Newswire Apr. 30, 2020.
10 Press release. Valneva Receives FDA Fast Track Designation for its Lyme Disease Vaccine Candidate VLA15. Valneva July 24, 2017.
11 Press release. Valneva Announces Positive Initial Results for Phase 2 Study of Lyme Disease Vaccine Candidate. Valneva July 22, 2020.
12 Parpia R. Lyme Disease Vaccines: Past and Future. The Vaccine Reaction July 18, 2020.
13 See Footnote 10.
14 See Footnote 11.
16 Valneva bags positive phase II results for Lyme disease vaccine. Pharma Times Oct. 22, 2020.
17 See Footnote 11.
18 See Footnote 16.
19 See Footnote 10.
20 See Footnote 11.
22 Lyme disease vaccine: Valneva reports positive second Phase 2 data. Outbreak News Today Oct. 21, 2020.
23 See Footnote 11.
24 Press release. Valneva and Pfizer Announce Collaboration to Co-Develop and Commercialize Lyme Disease Vaccine, VLA15. Valneva Apr. 30, 2020.
25 Flaharty B. Can a new Lyme disease vaccine overcome a history of distrust and failure? STAT Aug. 22, 2019.
26 New Lyme Disease Vaccine in Clinical trials: Update! Lyme Disease Association Apr. 26, 2019.
27 La Vigne P, Fisher BL. FDA Gives Green Light to Test Lyme Disease Vaccine on Humans. The Vaccine Reaction Jan. 26, 2017.
29 TVR Staff. Only One Percent of Vaccine Reactions Reported to VAERS. The Vaccine Reaction Jan. 9, 2020.
30 See Footnote 25.
31 Smith P. How the LYMErix Lyme Disease Vaccine was Pulled from the Market. Lymedisease.org.
32 Hard Science On Lyme: Do We Really Want Another Ospa Vaccine? Lymedisease.org Jan 14, 2014.
33 See Footnote 26.
34 Okie S. Lyme Disease Vaccine’s Safety Is Questioned. The Washington Post Apr. 8, 2001.
35 Washington J. Lyme disease vaccine discontinued, but new ways to prevent it are coming: Health Matters. Cleveland.com Jan. 26, 2020.