Reactivation of BK polyomavirus (BKPyV) can cause significant kidney and bladder disease in immunocompromised patients. There are currently no effective, BKPyV-specific therapies. MAU868 is a novel, human immunoglobulin (Ig) G1 monoclonal antibody that binds the major capsid protein, VP1, of BKPyV with picomolar affinity, neutralizes infection by the 4 major BKPyV genotypes (EC50 ranging from 0.009-0.093 μg/mL; EC90 ranging from 0.102-4.160 μg/mL), and has comparable activity against variants with highly prevalent VP1 polymorphisms. No resistance-associated variants were identified in long-term selection studies, indicating a high in vitro barrier-to-resistance. The high-resolution crystal structure of MAU868 in complex with VP1 pentamer identified 3 key contact residues in VP1 (Y169, R170, and K172). A first-in-human study was conducted to assess the safety, tolerability, and pharmacokinetics of MAU868 following intravenous and subcutaneous administration to healthy adults in a randomized, placebo-controlled, double-blinded, single ascending dose design. MAU868 was safe and well-tolerated. All adverse events were grade 1 and resolved. The pharmacokinetics of MAU868 was typical of a human IgG, with dose-proportional systemic exposure and an elimination half-life ranging between 23 and 30 days. These results demonstrate the potential of MAU868 as a first-in-class therapeutic agent for the treatment or prevention of BKPyV disease.

Biologic drugs are reshaping clinical practice in various disciplines, even while access to them is imbalanced across global settings. In sub-Saharan Africa, biotherapeutics have potential roles to play in the treatment of a range of conditions that include infectious and noncommunicable diseases (NCDs). However, the literature is scarce on guidance for addressing local access challenges, including technical, regulatory, affordability, and other healthcare delivery aspects. This article aims to assess fundamental determinants of use of biologic medicines in sub-Saharan Africa. The purpose is to inform strategic actions of scientists, physicians, policymakers, and other stakeholders that are working to improve access to innovative therapies in low resource parts of the world.

Biotherapeutics have become an essential component of the modern clinical armamentarium due in part to their high specificity and potency, but access to biotherapeutics is currently uneven across global settings.Compared with small molecule drugs, biotherapeutics have unique features that affect the way they are manufactured, supplied, and administered to patients.The disease burden in sub-Saharan Africa includes many communicable and noncommunicable disease indications for which biotherapeutics are already approved or are in clinical development.Technical, regulatory, health system, and economic factors all impact the safe and reliable access to biotherapeutics in sub-Saharan Africa. Biologic drugs are reshaping clinical practice in various disciplines, even while access to them is imbalanced across global settings. In sub-Saharan Africa, biotherapeutics have potential roles to play in the treatment of a range of conditions that include infectious and noncommunicable diseases (NCDs). However, the literature is scarce on guidance for addressing local access challenges, including technical, regulatory, affordability, and other healthcare delivery aspects. This article aims to assess fundamental determinants of use of biologic medicines in sub-Saharan Africa. The purpose is to inform strategic actions of scientists, physicians, policymakers, and other stakeholders that are working to improve access to innovative therapies in low resource parts of the world. Biologic drugs are reshaping clinical practice in various disciplines, even while access to them is imbalanced across global settings. In sub-Saharan Africa, biotherapeutics have potential roles to play in the treatment of a range of conditions that include infectious and noncommunicable diseases (NCDs). However, the literature is scarce on guidance for addressing local access challenges, including technical, regulatory, affordability, and other healthcare delivery aspects. This article aims to assess fundamental determinants of use of biologic medicines in sub-Saharan Africa. The purpose is to inform strategic actions of scientists, physicians, policymakers, and other stakeholders that are working to improve access to innovative therapies in low resource parts of the world.

Prion immunotherapy may hold great potential, but antibodies against certain PrP epitopes can be neurotoxic. Here we identified >6000 PrP-binding antibodies in a synthetic human Fab phage display library, 49 of which we characterized in detail. Antibodies directed against the flexible tail of PrP conferred neuroprotection against infectious prions. We then mined published repertoires of circulating B cells from healthy humans and found antibodies similar to the protective phage-derived antibodies. When expressed recombinantly, these antibodies exhibited anti-PrP reactivity. Furthermore, we surveyed 48’718 samples from 37’894 hospital patients for the presence of anti-PrP IgGs, and found 21 high-titer individuals. The clinical files of these individuals did not reveal any enrichment of specific pathologies, suggesting that anti-PrP autoimmunity is innocuous. The existence of protective anti-prion antibodies in unbiased human immunological repertoires, combined with the reported lack of such antibodies in carriers of disease-associated PRNP mutations, suggests a link to the low incidence of spontaneous prion diseases in human populations.

Human polyomaviruses cause a common childhood infection worldwide and typically elicit a neutralizing antibody and cellular immune response, while establishing a dormant infection in the kidney with minimal clinical manifestations. However, viral reactivation can cause severe pathology in immunocompromised individuals. We developed a high-throughput, functional antibody screen to examine the humoral response to BK polyomavirus. This approach enabled the isolation of antibodies from all peripheral B cell subsets and revealed the anti-BK virus antibody repertoire as clonally complex with respect to immunoglobulin sequences and isotypes (both IgM and IgG), including a high frequency of monoclonal antibodies that broadly neutralize BK virus subtypes and the related JC polyomavirus. Cryo-electron microscopy of a broadly neutralizing IgG single-chain variable fragment complexed with BK virus-like particles revealed the quaternary nature of a conserved viral epitope at the junction between capsid pentamers. These features unravel a potent modality for inhibiting polyomavirus infection in kidney transplant recipients and other immunocompromised patients.