Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.

Summary Human antibodies to HIV-1 can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection1,2. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time3,4. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design5-9. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice (hu-mice). Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies (bNAbs) can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy (ART)10-12, the longer half-life of antibodies led to viremic control for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in hu-mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals.

Antibodies against the CD4 binding site (CD4bs) on the HIV-1 spike protein gp120 can show exceptional potency and breadth. We determined structures of NIH45-46, a more potent clonal variant of VRC01, alone and bound to gp120. Comparisons with VRC01–gp120 revealed that a four-residue insertion in CDRH3 contributed to increased interaction between NIH45-46 and the gp120 inner domain, which correlated with enhanced neutralization. We used structure-based design to create NIH45-46G54W, a single substitution in CDRH2 that increases contact with the gp120 bridging sheet and improves breadth and potency, critical properties for potential clinical use, by an order of magnitude. Together with the NIH45-46–gp120 structure, these results indicate that gp120 inner domain/bridging sheet residues should be included in immunogens to elicit CD4bs antibodies.

Artificial intelligence (AI) is rapidly integrating into modern technology and clinical practice. Although in its nascency, AI has become a hot topic of investigation for applications in clinical practice. Multiple fields of medicine have embraced the possibility of a future with AI assisting in diagnosis and pathology applications. In the field of gastroenterology, AI has been studied as a tool to assist in risk stratification, diagnosis, and pathologic identification. Specifically, AI has become of great interest in endoscopy as a technology with substantial potential to revolutionize the practice of a modern gastroenterologist. From cancer screening to automated report generation, AI has touched upon all aspects of modern endoscopy. Here, we review landmark AI developments in endoscopy. Starting with broad definitions to develop understanding, we will summarize the current state of AI research and its potential applications. With innovation developing rapidly, this article touches upon the remarkable advances in AI-assisted endoscopy since its initial evaluation at the turn of the millennium, and the potential impact these AI models may have on the modern clinical practice. As with any discussion of new technology, its limitations must also be understood to apply clinical AI tools successfully. clin endosc 2020;53:132-141

Endoscopic ultrasound (EUS) is a minimally invasive diagnostic and therapeutic modality with a number of established as well as evolving uses in patients with chronic liver disease. Compared to other diagnostic tools such as cross-sectional imaging or conventional endoscopy, EUS has been shown to increase diagnostic sensitivity and therapeutic success for many clinical scenarios and applications with a low rate of adverse events. In this review, we discuss and focus on the current and growing role of EUS in the evaluation and/or treatment of hepatobiliary masses, hepatic parenchymal disease, portal hypertension, esophageal and other varices, and indeterminate biliary strictures.