Vaccination of natural reservoir hosts with recombinant lipidated OspA induces a transmission-blocking immunity against Lyme disease spirochaetes associated with high levels of LA-2 equivalent antibodies

Abstract

As observed in humans, immune responses in naturally infected reservoir hosts of Borrelia burgdorferi sensu lato rarely target the outer surface proteins (Osp) A and B of Lyme disease spirochaetes. The absence of protective immunity in such hosts following tick-borne infection allows them to play an effective role in the maintenance of Lyme borreliosis in nature. Therefore, the question was addressed whether one of the most prominent natural reservoir host species of B. burgdorferi s.l. in Europe, the yellow-necked mouse ( Apodemus flavicollis), may lack the ability to elicit transmission-blocking antibodies to Lyme borreliosis spirochaetes. Yellow-necked mice were immunized with a recombinant lipidated OspA from B. burgdorferi sensustricto or with high numbers of UV-irradiated whole spirochaetes. All immunized mice, but not untreated controls, developed polyclonal humoral immune responses to OspA (31 kDa). Serum antibodies of animals vaccinated with the recombinant OspA contained high levels of antibody to an epitope of OspA, defined by the monoclonal antibody LA-2, whereas only low levels of LA-2 equivalent antibodies could be detected in sera from animals immunized with killed spirochaetes. Ixodes ricinus ticks infected with B. burgdorferi s.s. lost their spirochaete load after feeding on animals with high levels of LA-2 equivalent antibody; ticks feeding on animals which had only low or undetectable serum levels of LA-2 equivalent antibodies retained their spirochaete infection. Furthermore, animals with high levels of LA-2 equivalent antibody were protected against spirochaete infection. Our study shows that natural mouse reservoir hosts are highly competent to generate transmission-blocking antibodies after vaccination with a lipidated recombinant OspA and indicates that antibodies to the LA-2 epitope play a key role in the destruction of B. burgdorferi s.s. within feeding Ixodes ricinus ticks.