Malte Braunschweig

Bio: Malte Braunschweig is an academic researcher from Rockefeller University. The author has contributed to research in topics: Viral load & Antibody. The author has an hindex of 4, co-authored 4 publications receiving 1071 citations. Previous affiliations of Malte Braunschweig include University of Freiburg & Howard Hughes Medical Institute.

Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117

Abstract: HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned. However, recently developed single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4, 5). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody, in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30 mg kg^(−1) infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8–2.5 log_(10) and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure.

HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption

Abstract: Interruption of combination antiretroviral therapy in HIV-1-infected individuals leads to rapid viral rebound. Here we report the results of a phase IIa open label clinical trial evaluating 3BNC117,a broad and potent neutralizing antibody against the CD4 binding site of the HIV-1 Env protein, during analytical treatment interruption in 13 HIV-1-infected individuals. Participants with 3BNC117-sensitive virus outgrowth cultures were enrolled. Results show that two or four 30 mg kg(-1) 3BNC117 infusions,separated by 3 or 2 weeks, respectively, are generally well tolerated.Infusions are associated with a delay in viral rebound of 5-9 weeks after two infusions, and up to 19 weeks after four infusions, or an average of 6.7 and 9.9 weeks, respectively, compared with 2.6 weeks for historical controls (P < 0.00001). Rebound viruses arise predominantly from a single provirus. In most individuals,emerging viruses show increased resistance, indicating escape.However, 30% of participants remained suppressed until antibody concentrations waned below 20 μg ml(-1), and the viruses emerging in all but one of these individuals showed no apparent resistance to 3BCN117, suggesting failure to escape over a period of 9-19 weeks.We conclude that the administration of 3BNC117 exerts strong selective pressure on HIV-1 emerging from latent reservoirs during analytical treatment interruption in humans.

HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1

Abstract: 3BNC117 is a broad and potent neutralizing antibody to HIV-1 that targets the CD4 binding site on the viral envelope spike. When administered passively, this antibody can prevent infection in animal models and suppress viremia in HIV-1–infected individuals. Here we report that HIV-1 immunotherapy with a single injection of 3BNC117 affects host antibody responses in viremic individuals. In comparison to untreated controls that showed little change in their neutralizing activity over a 6-month period, 3BNC117 infusion significantly improved neutralizing responses to heterologous tier 2 viruses in nearly all study participants. We conclude that 3BNC117-mediated immunotherapy enhances host humoral immunity to HIV-1.

Corrigendum: Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117.

Abstract: Nature 522, 487–491 (2015); doi:10.1038/nature14411 In this Letter, the grant U19AI111825-01 Cooperative Centers on Human Immunology from NIH was erroneously included in the Acknowledgments section; this has been corrected in the online versions of the paper.

COVID-19: combining antiviral and anti-inflammatory treatments

Abstract: 400 www.thelancet.com/infection Vol 20 April 2020 5 WHO. Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an empirical treatment during outbreaks. 2014. http://apps.who.int/iris/rest/ bitstreams/604045/retrieve (accessed Feb 20, 2020). 6 Arabi Y, Balkhy H, Hajeer AH. Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol. Springerplus 2015; 4: 709. 7 Hung IF, To KK, Lee CK, et al. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis 2011; 52: 447–56. 8 Hung IFN, To KKW, Lee CK, et al. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection. Chest 2013; 144: 464–73. 9 Mair-Jenkins J, Saavedra-Campos M, Baillie JK, et al. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis. J Infect Dis 2015; 211: 80–90. 10 Luke TC, Kilbane EM, Jackson JL, Hoffman SL. Meta-analysis: convalescent blood products for Spanish influenza pneumonia: a future H5N1 treatment? Ann Intern Med 2006; 145: 599–609. 15 Schoofs T, Klein F, Braunschweig M, et al. HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1. Science 2016; 352: 997–1001. 12 Lu CL, Murakowski DK, Bournazos S, et al. Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science 2016; 352: 1001–04. 13 WHO. Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected. 2020. https://www.who. int/docs/default-source/coronaviruse/clinical-management-of-novel-cov. pdf (accessed Feb 20, 2020). 14 Clark DR, Jonathan EM, JKB. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 2020; published online Feb 7. https://doi.org/10.1016/S0140-6736(20)30317-2.

Convalescent plasma as a potential therapy for COVID-19.

Abstract: 398 www.thelancet.com/infection Vol 20 April 2020 Control and Nursing in Guangdong Second Provincial General Hospital, have undergone intensive training to become familiar with the requirements for infection control in the negative pressure isolation wards. Herein, cameras cover the entire ward except for the privacy area. The infection control observer monitors medical staff in real time via computer monitors in a separate area (figure). The main responsibilities of the observer are to maintain the normal operation of the negative pressure isolation wards, supervise the implementation of disinfection, ensure a sufficient supply of protective materials, arrange specimens for inspection, and relieve anxiety of the medical personnel while treating patients. The observers pay attention to the medical staff not only during their time in the negative pressure ward, but also during the putting on or taking off of protective equipment when they enter or leave the ward. Although the health-care providers have attended multiple training sessions and emergency drills, in operation (especially in high-stress negative pressure wards) some steps might be omitted or overlooked, thus incurring potential exposure to nosocomial infection. For example, when a nurse helped an elderly patient pull up a zipper in the negative pressure ward, the zipper unexpectedly ripped the nurse’s glove. The nurse became nervous, and anxious to continue her procedures. Discovering this situation on screen, the observer immediately soothed the nurse and sent another staff member into the ward to assist. Following the occupational exposure process, the observer then instructed the nurse to remove her gloves carefully, disinfect her hands, and dispose of the ripped gloves. The observer also systematically assessed the risks for the nurse and arranged a quarantine room for medical observation to ensure full safety before she was allowed to return to the negative pressure ward. The observing system, as a proactive infection control tool, provides immediate prevention against nosocomial infection in negative pressure isolation wards, which offers creative assistance to combat the COVID-19 outbreak. Guangdong Second Provincial General Hospital plans to incorporate artificial intelligence image recognition into the observing system, aiming to enhance the sensitivity and accuracy of instant detection. Implementing and improving the observing system might be a promising endeavor for controlling nosocomial infection of the COVID-19 outbreak and other acute infectious diseases.

Follicular Helper T Cells

Abstract: Although T cell help for B cells was described several decades ago, it was the identification of CXCR5 expression by B follicular helper T (Tfh) cells and the subsequent discovery of their dependence on BCL6 that led to the recognition of Tfh cells as an independent helper subset and accelerated the pace of discovery. More than 20 transcription factors, together with RNA-binding proteins and microRNAs, control the expression of chemotactic receptors and molecules important for the function and homeostasis of Tfh cells. Tfh cells prime B cells to initiate extrafollicular and germinal center antibody responses and are crucial for affinity maturation and maintenance of humoral memory. In addition to the roles that Tfh cells have in antimicrobial defense, in cancer, and as HIV reservoirs, regulation of these cells is critical to prevent autoimmunity. The realization that follicular T cells are heterogeneous, comprising helper and regulatory subsets, has raised questions regarding a possible division of labor in germinal center B cell selection and elimination.

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society–USA Panel

Abstract: Importance New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. Objective To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. Evidence Review A panel of experts in HIV research and patient care convened by the International Antiviral Society–USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. Findings Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure. Conclusions and Relevance Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.

Prospective mapping of viral mutations that escape antibodies used to treat COVID-19.

Abstract: Antibodies are a potential therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the risk of the virus evolving to escape them remains unclear. Here we map how all mutations to the receptor binding domain (RBD) of SARS-CoV-2 affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino acid mutation that fully escapes the REGN-COV2 cocktail, which consists of two antibodies, REGN10933 and REGN10987, targeting distinct structural epitopes. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2 and during in vitro viral escape selections. Finally, the maps reveal that mutations escaping the individual antibodies are already present in circulating SARS-CoV-2 strains. These complete escape maps enable interpretation of the consequences of mutations observed during viral surveillance.