Early Lyme borreliosis sera with significant titers of anti-outer surface protein C (OspC) borreliacidal antibodies were identified. Human anti-OspC borreliacidal antibodies could be either IgM or IgG. Significant concentrations of borreliacidal activity were detected after vaccination of mice with OspC. Detection of anti-OspC borreliacidal activity was dependent on surface expression of OspC by Borrelia burgdorferi isolate 50772. The ability of OspC to induce borreliacidal antibodies in vivo and after vaccination offers another possible explanation for the ability of vaccination with OspC to protect against infection with B. burgdorferi. Furthermore, detection of anti-OspC borreliacidal antibodies, especially IgM antibodies, in early Lyme borreliosis sera provides additional evidence that borreliacidal antibody detection may be useful for the serodiagnosis of early Lyme borreliosis.

Groups of 15 laboratory-bred beagles were vaccinated and boosted with either a placebo or adjuvanted bivalent bacterin comprised of a traditional Borrelia burgdorferi strain and a unique ospA- and ospB-negative B. burgdorferi strain that expressed high levels of OspC and then challenged with B. burgdorferi-infected Ixodes scapularis ticks. The vaccinated dogs produced high titers of anti-OspA and anti-OspC borreliacidal antibodies, including borreliacidal antibodies specific for an epitope within the last seven amino acids at the OspC carboxy terminus (termed OspC7) that was conserved among pathogenic Borrelia genospecies. In addition, spirochetes were eliminated from the infected ticks that fed on the bacterin recipients, B. burgdorferi was not isolated from the skin or joints, and antibody responses associated specifically with canine infection with B. burgdorferi were not produced. In contrast, B. burgdorferi was recovered from engorged ticks that fed on 13 (87%) placebo-vaccinated dogs (P<0.0001), skin biopsy specimens from 14 (93%) dogs (P<0.0001), and joint tissue specimens from 8 (53%) dogs (P=0.0022). In addition, 14 (93%) dogs developed specific antibody responses against B. burgdorferi proteins, including 11 (73%) with C6 peptide antibodies (P<0.0001). Moreover, 10 (67%) dogs developed Lyme disease-associated joint abnormalities (P<0.0001), including 4 (27%) dogs that developed joint stiffness or lameness and 6 (40%) that developed chronic joint inflammation (synovitis). The results therefore confirmed that the bacterin provided a high level of protection against Lyme disease shortly after immunization.

Significant borreliacidal antibody was induced in volunteers and hamsters 60 days after primary and secondary vaccination with high concentrations of recombinant outer surface protein A (rOspA). However, the borreliacidal antibody response waned rapidly. Only 1 person had detectable cidal activity 180 days after vaccination. Similarly, the borreliacidal antibody response waned rapidly in hamsters by week 10 of vaccination. By contrast, the total anti-rOspA antibody response remained elevated in volunteers and hamsters. When isolates of Borrelia burgdorferi sensu lato were incubated in sera from vaccinated humans or hamsters, only the vaccine-specific isolate was killed. These results were confirmed by challenging rOspA-vaccinated hamsters with different isolates of B. burgdorferi sensu lato. The results showed that monitoring total rOspA antibody is inappropriate for evaluating the efficacy of an rOspA vaccine. The rOspA vaccine must be improved to yield comprehensive protection and maintain sustained levels of protective borreliacidal antibodies.

Borreliacidal antibodies specific for outer surface protein C (OspC) are induced shortly after infection with Borrelia burgdorferi. In this study, we identified the region of OspC recognized by immunoglobulin M (IgM) and IgG borreliacidal antibodies. Sera from patients with early Lyme disease were screened for borreliacidal activity specific for B. burgdorferi 50772 and OspC antibodies. Seven sera that contained similarly high titers of each response were then chosen randomly and adsorbed with OspC or a truncated OspC (OspC-Dra) containing the 50 amino acids nearest the carboxy terminus. Adsorption with OspC or OspC-Dra completely eliminated the borreliacidal activity in six (86%) of seven sera and significantly decreased the activity in the remaining serum (titer of 10,240 to 1,280). Moreover, OspC antibodies were no longer detected by OspC enzyme-linked immunosorbent assay or in a Western blot that contained native OspC. The findings confirmed that sera from patients with early Lyme disease contain high concentrations of IgM or IgG borreliacidal antibodies that bind a conserved region of OspC.

Our findings suggest that measurement of IFN-γ after incubating blood with Borrelia antigens could be useful in the laboratory diagnosis of early Lyme disease. Also, after antibiotic treatment, this response appears to be short lived.

College reopening decisions during the SARS-CoV-2 pandemic represent a trade-off between competing risks to students, faculty and staff, and college finances. Additionally, risks taken in reopening colleges can impose significant burdens on individuals living in surrounding communities. Many colleges that reopened for in-person instruction have reported frequent SARS-CoV-2 outbreaks. La Crosse County, Wisconsin experienced a substantial SARS-CoV-2 outbreak (2,002 cases in September 2020) that coincided with the return to in-person instruction at three local academic institutions. Genomic sequencing of SARS-CoV-2 cases in La Crosse during that period found rapid expansion of two viral substrains. Although the majority of cases were among college-age individuals, from a total of 111 genomes sequenced we identified rapid transmission of the virus into more vulnerable populations. Eight sampled genomes represented two independent transmission events into two skilled nursing facilities, resulting in two fatalities. Our study highlights the very significant risks imposed by college administrator reopening decisions, not just on college-associated populations, but on vulnerable individuals in surrounding communities.

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Highly specific borreliacidal antibodies are induced by infection with Borrelia burgdorferi, and a borreliacidal antibody test (BAT) may be an accurate laboratory procedure for confirming Lyme disease in clinical practice. To investigate this, 34 Lyme disease sera and 34 sera from patients with other illnesses who had presented to a primary-care facility located in an area of borreliosis endemicity were tested by the BAT and Western blotting (WB). The BAT was more sensitive (79% versus 65%; P ‫؍‬ 0.090), especially in cases in which patients had a single erythema migrans lesion (P ‫؍‬ 0.021). In addition, the potentially cross-reactive sera were negative by the BAT but WB yielded three (9%) false-positive results. The results from 104 sera from possible Lyme disease patients demonstrated the clinical usefulness of the more sensitive and specific BAT. The BAT was positive for 40 (38%) sera from patients with Lyme disease-related symptoms and appropriate clinical and epidemiological findings. WB confirmed Lyme disease in 30 (75%) of the 40 BAT-positive patients but failed to detect B. burgdorferi infection in 10 BAT-positive patients. WB was also positive for 11 BAT-negative sera, but six (55%) patients had case histories which suggested that the results were false positives. Collectively, the results confirm that the BAT is a sensitive and highly specific test and suggest that widespread use would increase the accuracy of serodiagnostic confirmation of Lyme disease.Lyme disease occurs after the bite of Borrelia burgdorferiinfected Ixodes spp. ticks. Detecting anti-B. burgdorferi antibodies in serum is the most commonly used method for confirming Lyme disease, since detecting the spirochetes by culture or PCR is problematic. The Centers for Disease Control and Prevention (CDC) recommends confirming Lyme disease by a two-tiered system, where serum is screened with an indirect immunofluorescence assay (IFA) or indirect enzymelinked immunosorbent assay. The serum with equivocal or positive results is then confirmed by immunoglobulin M (IgM) and IgG Western blotting (WB) or IgG WB alone if the illness has been present for less than or more than 1 month, respectively (14).WB can accurately confirm Lyme disease (21, 34, 35), especially when patients are tested who reside in a focus of endemicity and present with a tick exposure and well-recognized (13) clinical symptoms. However, false-positive WBs can occur (5, 15, 36) and the impact of the nonspecificity is magnified when the patients have less-typical symptoms or little risk of obtaining a tick bite (26,29,33,35). This shortcoming necessitates the development of a more accurate serodiagnostic test.Infection with B. burgdorferi induces the production of borreliacidal antibodies (6, 9-12, 17, 19, 24, 25, 30-32) that activate complement to form a membrane attack complex. The membrane attack complex then kills the spirochetes without the need for phagocytic cells (4,10,12,(22)(23)(24). Most B. burgdorferi proteins expressed on the surface of the spirochetes induce borrel...