Sera from Patients with Chronic Lyme Disease Protect Mice from Lyme Borreliosis

Abstract

Sera from selected patients with Lyme disease in different stages were used to passively immunize mice against Borrelia burgdorferi challenge to determine if human antibodies could protect the animals from infection. Sera from 2 patients with late-stage Lyme disease that contained strong antibody reactivity to proteins in B. burgdorferi lysates, including antibodies to the outer surface proteins (Osps) A and B, partly protected mice from infection after challenge with a small inoculum (10(2)) of B. burgdorferi. Mice immunized with sera from either of these 2 patients developed significantly fewer infections from the borreliae (patient 1 serum, 5%; patient 2 serum, 25%) relative to control mice (patient 1 serum, 90%; patient 2 serum, 74%). In contrast, sera from 2 patients with early or late Lyme disease that lacked antibodies reactive to OspA and OspB did not confer protection. Immunity appeared to be related, at least in part, to the presence of a strong humoral response to the Osps. These results suggest that during prolonged infection, some patients develop an immune response that may be partly protective against reinfection with B. burgdorferi. Therefore, although most patients do not mount a strong humoral response to the Osps during natural infection, vaccination with an Osp may elicit protective immunity.

Coinfection withBorrelia burgdorferiand the Agent of Human Granulocytic Ehrlichiosis Alters Murine Immune Responses, Pathogen Burden, and Severity of Lyme Arthritis

“…Antibodies have been shown to influence B. burgdorferi and HGE bacterial clearance and the course of Lyme arthritis (12,24,25,29,32,46,69). Our data show that CD4 ϩ T cells from coinfected mice had reduced levels of expression of CD40 ligand, an important costimulatory signal for B-cell activation, suggesting that antibody responses may be diminished.…”

“…In humans, the development of high-titer BBK32, also known as P35, antibodies during early-stage Lyme disease is associated with a decreased risk of progression to Lyme arthritis (31)(32)(33). Similarly, passive transfer of B. burgdorferi immune sera (12,29) can induce disease regression in mice, and outer surface protein C (OspC) (32), decorin-binding protein A (DbpA) (24), or BBK32 (28) antibodies can partially clear B. burgdorferi from an infected animal. Therefore, both the host humoral and cellular responses to B. burgdorferi can modify the course of spirochete infection and the severity of arthritis (41).…”

CD4+T Cells Promote Antibody Production but Not Sustained Affinity Maturation during Borrelia burgdorferi Infection

“…Thus, a lack of T cell activation or T FH cell differentiation is unlikely to be responsible for the previously observed failure to induce functional long-lived high-affinity T-dependent B cell responses during B. burgdorferi infection. Studies in humans (36), mice (37), and dogs (38) provide evidence that late in the infection the immune response eventually shifts toward the generation of long-lived antibodies and memory B cells. However, by then the bacteria are disseminated and may no longer be fully accessible to these later responses.…”

Destructive Arthritis in Vaccinated Interferon Gamma-Deficient Mice Challenged withBorrelia burgdorferi: Modulation by Tumor Necrosis Factor Alpha

“…By the same token, the fourfold decrease in the levels of borreliacidal antibody produced in anti-TNF-␣-treated vaccinated, challenged IFN-␥ 0 mice may have resulted in a failure to kill B. burgdorferi and prevent the induction of severe destructive arthritis. It is known that small changes in the levels of borreliacidal antibody can affect the induction of arthritis (22,27) and protection against infection (8,13,30,34). An alternative explanation is dependent on the effect of TNF-␣ on other effector molecules.…”