Lyme disease vaccines face familiar challenges, both societal and scientific

Abstract

Just over 20 years ago, a Lyme disease vaccine called LYMErix was approved for sale in the United States. Researchers designed the vaccine to prevent the transmission of the tick-borne pathogen Borellia burgdorferi, which spurs a bacterial infection that can cause fever, headaches, and joint pain if left untreated. LYMErix was on the market for just four years. Concerns over adverse reactions and a lukewarm reception from public health agencies led the vaccine's manufacturer, SmithKline Beecham, to shelve the product in 2002. Since then, the need for a vaccine has grown. An estimated 300,000 people are diagnosed with Lyme disease in the United States annually, and reported cases of the disease have tripled since the 1990s. In some counties in the northeast United States, disease incidence has increased more than 300% over a 20-year period. "The people who live along the northeast corridor among the Mississippi River valley have suffered greatly because there is no Lyme vaccine," says Gregory Poland, a vaccine researcher at the Mayo Clinic in Rochester, MN. Now, a new round of Lyme disease vaccines is in development. European biotech company Valneva is in phase 2 clinical trials for a vaccine against six strains of Borrelia, which causes the disease in Europe and the United States. And researchers are working to develop a vaccine against Lyme disease based on a vaccine for dogs that was released in 2016. The pressure is on this time around to make the "perfect vaccine," says immunologist Richard Marconi at the Virginia Commonwealth University in Richmond, one of the researchers working on the dog vaccine-inspired approach. The black-legged or deer tick (Ixodes scapularis) is responsible for transmitting Lyme disease in the northeast, mid-Atlantic, and north-central United States. Image credit: Shutterstock/Steven Ellingson.

Proteomic as an Exploratory Approach to Develop Vaccines Against Tick-Borne Diseases Using Lyme Borreliosis as a Test Case

“…They are based on whole-lysate antigens or recombinant OspC or OspA protein. In humans, clinical trials are underway in Europe using a modified OspA antigen [ 33 ]. The vaccine is based on six different OspA serotypes of different Borrelia species occurring in the United States and Europe and formulated with aluminum hydroxide [ 34 ].…”

Novel targets and strategies to combat borreliosis

“…It was hypothesized that the vaccine antigen, outer surface protein A (OspA), behaves as an autoantigen and therefore was arthritogenic. The adverse side effects were however never fully confirmed (Shaffer 2019).…”

Recent Progress in Lyme Disease and Remaining Challenges

“…The mechanism of action of this and other Osp-A based vaccines is antibody-mediated blocking of the transmission of Borreliella spirochetes from infected ticks while feeding on a human host (298,299). Public demand and acceptance of the vaccine was low for a variety of factors reviewed elsewhere (300)(301)(302)(303)(304) and Lymerix was pulled from the market by its manufacturer, Smith-Kline Beecham in 2002. Interest from industry waned and other efforts to develop Lyme vaccine candidates were also abandoned, including those by MedImmune, Baxter and Connaught Laboratories (300).…”

“…In a similar approach, a prototype vaccine that uses bacterial ferritin nanoparticles fused with seven serotypes of OspA molecules from Bb, B. afzelii, B. bavariensis and B. garinii recently showed durable high-titer antibody response in both mouse and rhesus macaque animal models (309). In both vaccine candidates, the antigenic residues in Osp-A serotype 1 that were previously suspected (221) but never shown to be cross-reactive were removed (304,309).…”