NOVEL VACCINES FOR LYME DISEASE AND OTHER TICK - BORNE PATHOGENS RICHARD MARCONI, PHD Dr. Marconi, a professor in the department of Microbiology and Immunology at the Virginia Commonwealth University Medical Center, presented a 1 hour webinar reviewing Lyme disease and discussing novel vaccines for tick-borne pathogens.
KEY HIGHLIGHTS
1 Lyme disease is the most common arthropod-borne disease in North America and Europe. In the past 2 years, the number of diagnosed or probable cases per year in humans has increased by nearly 30% to approximately 437,000. 2 The causative agent of Lyme disease in N. America is Borrelia burgdorferi ; a spirochete that is transmitted to mammals by Ixodes ticks. Because Lyme disease can not be transmitted from animal to animal and since the spirochetes are not transovarially transmitted in ticks, persistence of these unique bacteria in nature requires that they cycle back and forth between ticks and mammals. When the 6 legged larval stage ticks emerge from the egg, they are infection-free and can only become infected if they feed on an infected animal. After larval ticks take a single bloodmeal they molt to the 8 legged nymphal ticks. Nymphs are the first developmental stage of the tick that can transmit Lyme disease to a mammal. After feeding, nymphs molt to sexually di ff erentiated adult ticks. Since adult male ticks do not feed, it is only the adult female tick that can transmit Lyme disease to another animal. 3 When the Lyme spirochetes are exposed to blood during tick feeding, they switch from producing OspA (Outer surface protein A) to producing OspC (Outer surface protein C). This change in their “protein coat”
animals and this requires frequent booster vaccinations. 6 The rationale behind VANGUARD crLyme was to develop a vaccine that can protect through two synergistic mechanisms: killing of spirochetes in BOTH ticks and mammals. The crLyme vaccine consists of purified recombinant OspA and a unique recombinant OspC derived protein called a “chimeritope” (chimeric epitope based protein). An inherent challenge associated with using a single OspC variant as a vaccine antigen is that OspC is a highly variable protein. To overcome OspC diversity, the immunologically important segments of several di ff erent OspC protein variants were identified and fused together to make a custom designed OspC derived protein that can stimulate the production of antibodies that can target diverse B. burgdorferi strains. 7 VANGUARDcrLyme is intended for use in dogs 8 weeks of age or older to aid in the prevention of clinical disease and sub-clinical arthritis associated with B. burgdorferi infection. Dogs should be administered two doses three weeks apart with annual revaccination recommended. VANGUARDcrLyme has a 15 month duration of immunity label: the longest of ANY USDA approved Lyme disease vaccine. LEARN MORE
is an essential step that must occur in order for the spirochetes to exit the tick and infect mammals. This important information proved central in e ff orts to develop a vaccine that can kill spirochetes in both ticks and in mammals. 4 There are two types of canine Lyme disease vaccines: bacterins and subunit vaccines. Bacterins consist of homogenized bacterial cell lysates that are inactivated (killed) and filtered. A typical Lyme disease bacterin or “bacterial soup” vaccine contains in excess of 1,000 di ff erent proteins. However, only a small subset of these proteins contribute to protective immunity. In contrast, Lyme subunit vaccines consist of one or two highly purified and well characterized proteins. Hence, subunit vaccines are well defined in terms of their composition and lack “extraneous” bacterial ingredients. Intuitively, a cleaner subunit vaccine would be less prone to trigger adverse events. 5 Until 2016, the only available Lyme subunit vaccine was Recombitek Lyme (Merial). This vaccine consists of OspA, a protein that is produced by the Lyme disease spirochetes in ticks but not in mammals. Hence, antibody to OspA can only target spirochetes inside ticks. It cannot target spirochetes that successfully pass into a mammal. Complete killing of spirochetes in ticks requires that high levels of antibody be maintained in the blood of vaccinated
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