Vectorborne diseases account for more than 17 percent of all infectious diseases worldwide, causing over 700,000 deaths annually and leaving millions more with chronic, debilitating conditions, according to the World Health Organization. These illnesses are spread by a variety of arthropods — mosquitoes, ticks, and fleas — and even some mammals can serve as reservoirs for the pathogens they carry.
In North America and Europe, the most prevalent vector-borne infection is still Lyme disease, caused by the spiral-shaped bacterium Borrelia burgdorferi, which is transmitted by the black-legged tick. Each year, over 476,000 Americans are diagnosed and treated, though millions more may struggle with persistent or chronic symptoms.
Ticks have steadily expanded their geographic range in recent decades, driven largely by climate change, accelerated trade, and shifting ecosystems. “Clinicians are increasingly diagnosing locally acquired cases in regions previously considered low risk, including the southeastern US, reflecting a broader expansion of tick populations rather than isolated travel-related exposure,” Seth Lederman, CEO of Tonix Pharmaceuticals, told DDN.
Early-stage Lyme disease can be subtle and easily overlooked, with symptoms such as fatigue, fever, headache, and sometimes the hallmark rash going unnoticed. If left untreated, the infection can spread through the body, leading to chronic complications that affect the skin, joints, heart, and nervous system, and in some cases can cause long-term, debilitating effects.
“The stakes are even higher for children, in whom the infection can invade the central nervous system, potentially altering neurodevelopment and having long-lasting effects on cognitive and neurological health,” Lederman said.
However, despite rising case numbers and expanding risk, options for preventing infection remain limited, leaving individuals largely reliant on personal protective measures such as repellents, clothing barriers, and tick checks.
The search for a Lyme disease vaccine
Since the withdrawal of the LYMErix vaccine in 2002, due to safety concerns and limited public adoption, there has been no approved vaccine for human use. This has left a significant gap in protection for populations at risk, particularly those living in or traveling to areas where ticks are endemic. The rising prevalence of Lyme disease and the expansion of tick habitats have renewed urgency in the development of safe, effective preventive strategies, including innovative vaccines and novel prophylactic therapies.
Pfizer and Valneva are developing PF-07307405, a next-generation vaccine that builds on the approach first used by LYMErix. Like its predecessor, PF-07307405 delivers the protein OspA (outer surface protein A) of Borrelia burgdorferi, stimulating the immune system to generate protective antibodies. Because OspA is expressed on the bacterium while it resides in the tick’s midgut, these antibodies can neutralize the bacteria during the tick’s blood meal, effectively blocking transmission before infection occurs in humans.
In recent Phase 3 trials, the vaccine showed about 75 percent efficacy in preventing Lyme disease after four doses administered over two tick seasons. While the trial did not meet all pre-specified statistical endpoints, Pfizer described the results as clinically meaningful and expressed confidence in the vaccine’s potential, with plans to submit data to regulatory authorities.
One major improvement over LYMErix is the scope of protection. While LYMErix targeted a single OspA serotype, PF-07307405 covers the six most prevalent serotypes found across North America and Europe, broadening its potential effectiveness in a global context.
A faster response
Despite these advances, PF-07307405 still relies on a multi-dose schedule over an extended period, meaning that full protection is not immediate. For individuals seeking rapid or seasonal protection — such as outdoor workers, hikers, or residents entering high-risk areas — this delay can leave a critical window of vulnerability. Recognizing this need, Tonix Pharmaceuticals has developed TNX-4800, a long-acting monoclonal antibody designed to provide immediate, passive immunity against Lyme disease.
Unlike traditional vaccines, TNX-4800 delivers pre-formed antibodies targeting OspA. These antibodies circulate in the bloodstream within two days of administration and neutralize the bacteria inside the tick’s midgut when a blood meal occurs, preventing transmission to the human host.
“Our approach is more homogeneous,” Lederman said. “Everyone who receives it should experience a similar level of protection, whereas vaccines rely on an individual’s immune response, which can vary — particularly in older adults or those with certain health conditions.”
Phase 1 trials of TNX-4800 demonstrated that a single subcutaneous dose was safe, well-tolerated, and rapidly absorbed, with measurable protective levels persisting for approximately four months. The engineered extended half-life of the antibody supports sustained immunity throughout peak tick season with just one injection. This approach eliminates the need for complex, multi-dose schedules and offers a potentially more practical option for seasonal or high-risk protection, particularly for populations who might struggle to complete a longer vaccination regimen.
Killing the tick itself
Both of these approaches only protect against Lyme disease, and not the number of other pathogens that can be transmitted by the same ticks, such as the Powassan virus or the parasite that causes babesiosis.
Tarsus Pharmaceuticals is developing an innovative oral prophylactic therapy, TP-05, which targets the tick directly rather than the bacterium. TP-05 is an oral formulation intended to rapidly provide systemic blood levels of lotilaner, a well-characterized anti-parasitic agent, that kills ticks before they can transmit Borrelia burgdorferi. By eliminating the tick itself, this strategy could theoretically reduce transmission of multiple pathogens simultaneously, including Borrelia burgdorferi, Babesia species, Anaplasma, and Powassan virus.
In preclinical and early clinical studies, TP-05 demonstrated rapid tick mortality and favorable safety profiles. The ongoing Calliope Phase 2 trial is evaluating the safety, tolerability, and pharmacokinetics of orally administered TP-05 in approximately 700 participants across endemic US regions. If successful, this could represent the first on-demand, non-vaccine pharmacologic option to prevent Lyme disease by targeting the vector directly.
A multi-pronged approach to tick-borne disease prevention
For decades, the focus has been on treating infections after they occur, often relying on antibiotics to mitigate progression. Now, science is moving toward stopping disease at the source.
Vaccines like VLA15, monoclonal antibodies like TNX-4800, and oral therapies like TP-05 offer complementary strategies. Vaccines provide long-term adaptive immunity, monoclonal antibodies deliver rapid, seasonal protection, and oral prophylactics aim to neutralize ticks before transmission. Combined with traditional preventive measures — clothing, repellents, and tick checks — these therapies could dramatically reduce the incidence of Lyme disease.
Lyme disease is rarely fatal, but it can cause long-term, debilitating complications if left untreated. With the geographic range of ticks expanding due to climate change and public awareness lagging, these new interventions could represent the most significant public health advance against Lyme disease in decades.
