Wednesday, March 31, 2010

A fresh approach towards a Lyme disease vaccine: targeting the tick

We tend to focus on the pathogen when thinking about how the immune system responds to tick-borne infections.  Ticks also provoke an immune response, even those that don't harbor any infectious agent.  Animals that are repeatedly bitten by ticks will eventually develop immunity to the tick.  There's even a commercial tick vaccine called TickGARD, which protects cattle against infestation by the tick Boophilus microplus.  TickGARD is formulated with a protein located in the midgut of B. microplus.

Animals that are immune to ticks also resist infection by some tick-borne pathogens, including Borrelia burgdorferi (Nazario et al., 1998).  Vaccines designed from a single tick component may also protect host animals from infectious agents.  A tick vaccine formulated with the tick cement protein 64TRP protected mice from being killed by the tick-borne encephalitis virus introduced by its vector, Ixodes ricinus (Labuda et al., 2006).

These earlier studies prompted Erol Fikrig's group at Yale to devise a vaccine that targets an Ixodes tick protein required by B. burgdorferi for a successful infection.  They focused on Salp15, a protein found in tick saliva.  Salp15 binds to the B. burgdorferi surface protein OspC as the spirochete passes through the salivary gland on its way into the skin of the victim.  Salp15 is one of the many bioactive salivary proteins that dampen the immune system to allow the tick to remain attached for several days so that it could complete its blood meal.  B. burgdorferi exploits Salp15 to fend off the immune response in the early stages of infection.  Since Salp15 coats B. burgdorferi, a vaccine targeting Salp15 could make B. burgdorferi vulnerable to killing by the immune system.  Indeed, Salp15 antiserum was able to enhance phagocytosis of Salp15-coated B. burgdorferi by mouse macrophages in vitro.

Despite the promising in vitro results, Salp15 as a vaccine was only partially protective in animal studies.  55-60% of mice actively immunized with Salp15 or passively immunized with Salp15 antiserum ended up infected with B. burgdorferi following challenge with infected Ixodes scapularis ticks.  Moreover, ticks were able to feed normally on mice immunized with Salp15, indicating that the animals did not acquire tick immunity.

Where Salp15 shined was in improving the efficacy of another Lyme vaccine.  The OspA vaccine requires several doses to achieve maximum protection against B. burgdorferi.  When Salp15 was combined with OspA, a single dose of the mixture spared 70% of mice from infection, whereas only 10-20% of mice immunized with a single dose of OspA or OspA plus Salp25D (an irrelevant tick salivary protein) were protected.  Thus future Lyme disease vaccines that target a component of the spirochete could also include Salp15 to enhance their protective capacity.

Scientists are undoubtedly examining other tick proteins as potential vaccines against ticks and the pathogens they transmit.

Featured paper

Dai, J., Wang, P., Adusumilli, S., Booth, C.J., Narasimhan, S., Anguita, J., and Fikrig, E. (November 19, 2009).  Antibodies against a tick protein, Salp15, protect mice from the Lyme disease agent.  Cell Host & Microbe 6:482-492.  DOI: 10.1016/j.chom.2009.10.006

Other references

Labuda, M., Trimnell, A.R., Licková, M., Kazimírová, M.,Davies, G.M., Lissina, O., Hails, R.S., and Nuttall, P.A. (April 2006).  An antivector vaccine protects against a lethal vector-borne pathogen.  PLoS Pathogens 2(4):e27.  DOI: 10.1371/journal.ppat.0020027

Nazario, S., Das, S., De Silva, A.M., Deponte, K., Marcantonio, N., Anderson, J.F., Fish, D., Fikrig, E., and Kantor, F.S. (June 1998).  Prevention of Borrelia burgdorferi transmission in guinea pigs by tick immunity.  American Journal of Tropical Medicine and Hygiene 58(6):780-785.  Link

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