• Pre-exposure Prophylaxis With OspA-Specific Human Monoclonal Antibodies Protects Mice Against Tick Transmission of Lyme Disease Spirochetes

      Wang, Yan; Kern, Aurelie; Boatright, Naomi; Schiller, Zachary; Sadowski, Andrew; Monir, Ejemel; Souders, Colby; Reimann, Keith A.; Hu, Linden; Thomas, William D. Jr.; et al. (2016-07-15)
      BACKGROUND: Tick transmission of Borrelia spirochetes to humans results in significant morbidity from Lyme disease worldwide. Serum concentrations of antibodies against outer surface protein A (OspA) were shown to correlate with protection from infection with Borrelia burgdorferi, the primary cause of Lyme disease in the United States. METHODS: Mice transgenic for human immunoglobulin genes were immunized with OspA from B. burgdorferi to generate human monoclonal antibodies (HuMabs) against OspA. HuMabs were generated and tested in in vitro borreliacidal assays and animal protection assays. RESULTS: Nearly 100 unique OspA-specific HuMabs were generated, and 4 HuMabs (221-7, 857-2, 319-44, and 212-55) were selected as lead candidates on the basis of borreliacidal activity. HuMabs 319-44, 857-2, and 212-55 were borreliacidal against 1 or 2 Borrelia genospecies, whereas 221-7 was borreliacidal (half maximal inhibitory concentration, < 1 nM) against B. burgdorferi, Borrelia afzelii, and Borrelia garinii, the 3 main genospecies endemic in the United States, Europe, and Asia. All 4 HuMabs completely protected mice from infection at 10 mg/kg in a murine model of tick-mediated transmission of B. burgdorferi CONCLUSIONS: Our study indicates that OspA-specific HuMabs can prevent the transmission of Borrelia and that administration of these antibodies could be employed as preexposure prophylaxis for Lyme disease.
    • Preexposure Prophylaxis for the Prevention of HIV Infection: US Preventive Services Task Force Recommendation Statement

      US Preventive Services Task Force; Owens, Douglas K.; Pbert, Lori; Wong, John B. (2019-06-11)
      Importance: An estimated 1.1 million individuals in the United States are currently living with HIV, and more than 700000 persons have died of AIDS since the first cases were reported in 1981. In 2017, there were 38281 new diagnoses of HIV infection reported in the United States; 81% of these new diagnoses were among males and 19% were among females. Although treatable, HIV infection has no cure and has significant health consequences. Objective: To issue a new US Preventive Services Task Force (USPSTF) recommendation on preexposure prophylaxis (PrEP) for the prevention of HIV infection. Evidence Review: The USPSTF reviewed the evidence on the benefits of PrEP for the prevention of HIV infection with oral tenofovir disoproxil fumarate monotherapy or combined tenofovir disoproxil fumarate and emtricitabine and whether the benefits vary by risk group, population subgroup, or regimen or dosing strategy; the diagnostic accuracy of risk assessment tools to identify persons at high risk of HIV acquisition; the rates of adherence to PrEP in primary care settings; the association between adherence and effectiveness of PrEP; and the harms of PrEP when used for HIV prevention. Findings: The USPSTF found convincing evidence that PrEP is of substantial benefit in decreasing the risk of HIV infection in persons at high risk of HIV acquisition. The USPSTF also found convincing evidence that adherence to PrEP is highly associated with its efficacy in preventing the acquisition of HIV infection; thus, adherence to PrEP is central to realizing its benefit. The USPSTF found adequate evidence that PrEP is associated with small harms, including kidney and gastrointestinal adverse effects. The USPSTF concludes with high certainty that the magnitude of benefit of PrEP with oral tenofovir disoproxil fumarate-based therapy to reduce the risk of acquisition of HIV infection in persons at high risk is substantial. Conclusions and Recommendation: The USPSTF recommends offering PrEP with effective antiretroviral therapy to persons at high risk of HIV acquisition. (A recommendation).