T helper cell priming of mice toBorrelia burgdorferiOsp A leads to induction of protective antibodies following experimental but not tickborne infection

摘要

AbstractAntibodies to the outer surface lipoprotein A (Osp A) ofBorrelia burgdorfericonfer protection to SCID mice against subsequent tick‐borne or experimental infection. However, Osp A‐specific antibodies are hardly detectable in naturally infected humans, dogs, hamsters and mice. This is most probably due to limited expression of Osp A on spirochetes transmitted from the vector to the host. Here we have tested whether T cell priming of mice would lead to the induction of protective Osp A‐specific antibodies upon infection. It is shown that AKR/N mice, previously immunized with either a single T helper cell peptide of Osp A, or a mixture of 27 peptides spanning the entire molecule, develop Osp A‐specific IgM or IgG antibodies, including those to a prominent protective B cell epitope of Osp A, LA‐2, within 7 days of infection with low doses (103) of culture‐derived spirochetes. In marked contrast, the same groups of pre‐sensitized mice failed to generate any detectable Osp A‐specific antibodies after tick‐borne infection for more than 40 days after infection. All mice, irrespective of their state of T cell immunity to OspA or the mode of infection, produced similar levels of Osp C‐specific IgM and IgG antibodies as early as day 14 after infection. None of the mice previously immunized with Osp A peptides were protected against experimental infection, in spite of the appearance of protective antibodies. It is clear from these data that, in contrast to culture‐derived spirochetes, the naturally transmitted pathogen fails to express Osp A within the mammalian host at levels sufficient for induction of B cell responses, even in the presence of pre‐activated T helper cells. Together with the fact that Osp A‐specific antibodies are mainly operative by eliminating spirochetes from the vector during infestation, the data suggest that Osp A‐vaccination for T helper cell immunity alone is not suffici