The novel Lyme borreliosis vaccine VLA15 shows broad protection against Borrelia species expressing six different OspA serotypes

Abstract

We have previously shown that the Outer surface protein A (OspA) based Lyme borreliosis vaccine VLA15 induces protective immunity in mice. Herein, we report the induction of protective immunity by VLA15 with mouse models using ticks infected with B. burgdorferi (OspA serotype 1), B. afzelii (OspA serotype 2) and B. bavariensis (OspA serotype 4) or with in vitro grown B. garinii (OspA serotype 5 and 6) for challenge. For B. garinii (OspA serotype 3), we have developed a growth inhibition assay using chicken complement and functional antibodies targeting B. garinii (OspA serotype 3) could be demonstrated after immunization with VLA15. Furthermore, following three priming immunizations, a booster dose was administered five months later and the induction of immunological memory could be confirmed. Thus, the antibody titers after the booster dose were increased considerably compared to those after primary immunization. In addition, the half-lives of anti-OspA serotype specific antibodies after administration of the booster immunization were longer than after primary immunization. Taken together, we could show that VLA15 induced protection in mice against challenge with four different clinically relevant Borrelia species (B. burgdorferi, B. afzelii, B. garinii and B. bavariensis) expressing five of the six OspA serotypes included in the vaccine. The protection data is supported by functional assays showing efficacy against spirochetes expressing any of the six OspA serotypes (1 to 6). To our knowledge, this is the first time a Lyme borreliosis vaccine has been able to demonstrate such broad protection in preclinical studies. These new data provide further promise for the clinical development of VLA15 and supports our efforts to provide a new Lyme borreliosis vaccine available for global use.

Fig 1. Growth inhibition of B. garinii (ST3).

The growth inhibition of B. garinii (ST3) strain PFr in the presence of either immune sera from mice immunized with VLA15 or full length OspA (ST3, Lip-OspA3-His) are shown. The maximum level of growth, 100% (solid line), is defined as the growth observed in the presence of serum from placebo immunized mice. In addition, 50% spirochete growth is indicated (dotted line). VLA15 immune sera and full length OspA ST3 immune sera showed similar levels of growth inhibition.

Fig 2. Long-term persistence of anti-OspA antibodies and the effect of a booster immunization.

Mice were immunized subcutaneously three times with 3.0 μg (-●-), 0.3 μg (-■-) or 0.03 μg (-▲-) VLA15 formulated with 0.15% aluminium hydroxide with two week intervals. Five months after the third priming immunization, a booster immunization was administered, indicated with an arrow on the time scale. Blood was collected monthly for one year and the total OspA serotype specific IgG titers determined with endpoint ELISA, where the plates were coated with full length OspA (Lip-OspA-His) of the corresponding serotype. (A) B. burgdorferi (ST1), (B) B. afzelii (ST2), (C) B. garinii (ST3), (D) B. bavariensis (ST4), (E) B. garinii (ST5), (F) B. garinii (ST6). (G) Anti-OspA antibody titer half-lives in weeks after primary immunization (week 8 to 28) and after booster immunization (week 36 to 52), respectively.