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Articles by Ben Murrell
Prophylactic treatment with broadly neutralizing antibody VRC01 selects for escape mutants after infection in Antibody-Mediated Prevention trials
Abstract Broadly neutralizing antibodies (bnAbs) show promise in HIV prevention, yet viral escape remains a challenge. In the Antibody-Mediated Prevention (AMP) trials, the CD4 binding site (CD4bs) bnAb VRC01 blocked acquisition by VRC01-sensitive strains. However, its influence on viral evolution post acquisition is not fully understood.
Long-read deep sequencing reveals high rates of multilineage transmission and rapid viral population changes in acute HIV infection
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Abstract Understanding the selective forces acting upon HIV early in infection is crucial to design prevention strategies. By leveraging deep sequencing and the short diagnostic intervals of the FRESH and RV217 cohorts between the last-negative and first-positive RNA tests (median 4 days), we captured a precise and early snapshot of acute HIV infection.
By James Mullins, Wenjie Deng, Elena Giorgi, Craig A Magaret, Morgane Rolland, Tanmoy Bhattacharya, Dylan Westfall, Anna Yssel, Roger E. Bumgarner, Ben Murrell, Thumbi Ndung’u, Merlin L. Robb, Raabya Rossenkhan, Paul T. Edlefsen, Krista L Dong, Lennie Chen, Asanda Gwashu-Nyangiwe, Hong Zhao, Ruwayhida Thebus, Nonkululeko Ndabambi, Sorachai Nitayaphan, Talita York, David Matten, Hugh Murrell, Alec Pankow, Michal Juraska, James Ludwig, John Hural, Myron Cohen, Lawrence Corey, M. Juliana McElrath, Peter Gilbert, Carolyn Williamson, Bruna Galvao, Fredrick Sawe
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Nature
Verified
Computer Science > Machine Learning
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Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials
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Abstract In the antibody mediated prevention (AMP) trials, the broadly neutralizing antibody (bNAb) VRC01 demonstrated protective efficacy against susceptible HIV strains. To understand how VRC01 shaped breakthrough infections, deep sequencing was performed on 172 participants (>100,000 gag-Δpol and rev-env-Δnef sequences), at diagnosis and over time, in the placebo and treatment arms of the African (HVTN703/HPTN081; NCT02568215) and Americas/Europe (HVTN704/HPTN085; NCT02716675) cohorts.
By Carolyn Williamson, Chivonne Moodley, Craig A Magaret, Elena Giorgi, Morgane Rolland, Dylan Westfall, Anna Yssel, Wenjie Deng, Nonhlanhla N. Mkhize, Lennie Chen, Hong Zhao, Tanmoy Bhattacharya, Alec Pankow, Ben Murrell, Ruwayhida Thebus, Paula Cohen Verified, Bronwen E. Lambson, Michal Juraska, Hongjun Bai, Allan C. deCamp, Maurine D Miner, James Ludwig, Yunda Huang, Lily Zhang, Daniel Reeves, Bryan Mayer, Shelly Karuna, John Hural, Lynn Morris, David C. Montefiori, Penny Moore, Paul T. Edlefsen, Srilatha Edupuganti, Nyaradzo Mgodi, M. Juliana McElrath, Myron Cohen, Lawrence Corey, Peter Gilbert, James Mullins, Raabya Rossenkhan, Talita York, Asanda Gwashu-Nyangiwe, Nonkululeko Ndabambi, Haajira Kaldine, Sinethemba Bhebhe, Cindy Molitor, Nicolas Beaume, David Matten, Roger E. Bumgarner
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Nature
Verified
[2511.16599] Time dependent loss reweighting for flow matching and diffusion models is theoretically justified
arXivLabs is a framework that allows collaborators to develop and share new arXiv features directly on our website. Both individuals and organizations that work with arXivLabs have embraced and accepted our values of openness, community, excellence, and user data privacy. arXiv is committed to these values and only works with partners that adhere to them. Have an idea for a project that will add value for arXiv's community? Learn more about arXivLabs.
Detection of PCR chimeras in adaptive immune receptor repertoire sequencing using hidden Markov models
Abstract Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) has emerged as a central approach for studying T cell and B cell receptor populations, and is now an important component of studies of autoimmunity, immune responses to pathogens, vaccines, allergens, and cancers, and for antibody discovery.
Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques - Nature Communications
Abstract The continued evolution of SARS-CoV-2 underscores the need to understand qualitative aspects of the humoral immune response elicited by spike immunization. Here, we combine monoclonal antibody (mAb) isolation with deep B cell receptor (BCR) repertoire sequencing of rhesus macaques immunized with prefusion-stabilized spike glycoprotein.
Spike deep mutational scanning helps predict success of SARS-CoV-2 clades - Nature
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Abstract SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion1 and affect other properties that contribute to viral fitness, such as ACE2 receptor binding and cell entry2,3. Knowledge of how mutations affect these spike phenotypes can provide insight into the current and potential future evolution of the virus.
By Bernadeta Dadonaite, Cameron Stewart Verified, Jenni Logue, Ben Murrell, Helen Y. Chu, David Veesler
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Nature
Verified
Three immunizations with Novavax’s protein vaccines increase antibody breadth and provide durable protection from SARS-CoV-2 - npj Vaccines
Abstract The immune responses to Novavax’s licensed NVX-CoV2373 nanoparticle Spike protein vaccine against SARS-CoV-2 remain incompletely understood. Here, we show in rhesus macaques that immunization with Matrix-MTM adjuvanted vaccines predominantly elicits immune events in local tissues with little spillover to the periphery.
SARS-CoV-2 evolution in the Omicron era - Nature Microbiology
Abstract Since SARS-CoV-2 BA.5 (Omicron) emerged and spread in 2022, Omicron lineages have markedly diversified. Here we review the evolutionary trajectories and processes that underpin the emergence of these lineages, and identify the most prevalent sublineages. We discuss the potential origins of second-generation BA.2 lineages. Simple and complex recombination, antigenic drift and convergent evolution have enabled SARS-CoV-2 to accumulate mutations that alter its antigenicity.
Antigen pressure from two founder viruses induces multiple insertions at a single antibody position to generate broadly neutralizing HIV antibodies
Structural consequences of the CDRH1 insertion Since the development of neutralization breadth was associated with an insertion of varying length at CDRH1, we sought to investigate the consequences of the insertion on antibody structure. X-ray crystal structures were solved for three 11aa-insertion Fabs (17A, 23D and 50I) and three 4 aa-insertion (group 4b) Fabs (50E, 55C and 50L) and the PC39-1 lineage UCA Fab. Each PC39-1 mAb is named after the timepoint (in mpi) at which it was isolated.
Vaccination of SARS-CoV-2-infected individuals expands a broad range of clonally diverse affinity-matured B cell lineages - Nature Communications
Abstract Vaccination of SARS-CoV-2 convalescent individuals generates broad and potent antibody responses. Here, we isolate 459 spike-specific monoclonal antibodies (mAbs) from two individuals who were infected with the index variant of SARS-CoV-2 and later boosted with mRNA-1273. We characterize mAb genetic features by sequence assignments to the donors’ personal immunoglobulin genotypes and assess antibody neutralizing activities against index SARS-CoV-2, Beta, Delta, and Omicron variants.
An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction
Abstract SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this interaction presents an attractive possibility for suppressing SARS-CoV-2 replication. Here, we report the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement.
HIV Superinfection Drives De Novo Antibody Responses and Not Neutralization Breadth
Eliciting antibodies that neutralize a broad range of circulating HIV strains (broadly neutralizing antibodies [bnAbs]) represents a key priority for vaccine development. HIV superinfection (re-infection with a second strain following an established infection) has been associated with neutralization breadth, and can provide insights into how the immune system responds to sequential exposure to distinct HIV envelope glycoproteins (Env).
HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage
PCT64 LMCA Ab Binds to Early Autologous Env Trimers Only When Devoid of Complex and Hybrid Glycans Recent publications offer hope that rational, structure-based HIV vaccine strategies, based on germline targeting followed by sequential immunizations with guide immunogens, might succeed (Briney et al., 2016bxTailored immunogens direct affinity maturation toward hiv neutralizing antibodies.
Intrapatient viral diversity and treatment outcome in patients with genotype 3a hepatitis C virus infection on sofosbuvir-containing regimens
Treatment with the direct-acting antiviral agent (DAA) sofosbuvir (SOF), an NS5B inhibitor, and velpatasvir (VEL), an NS5A inhibitor, demonstrates viral cure rates of ?95% in hepatitis C virus (HCV) genotypes (GT) 1-6. Here we investigated intrapatient HCV diversity in NS5A and NS5B using Shannon entropy to examine the relationship between viral diversity and treatment outcome.
Less Is More: An Adaptive Branch-Site Random Effects Model for Efficient Detection of Episodic Diversifying Selection
Over the past two decades, comparative sequence analysis using codon-substitution models has been honed into a powerful and popular approach for detecting signatures of natural selection from molecular data. A substantial body of work has focused on developing a class of “branch-site” models which permit selective pressures on sequences, quantified by the ω ratio, to vary among both codon sites and individual branches in the phylogeny.
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