Daniel J. Sheward
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View article: Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2
Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2 Open
The COVID-19 pandemic showcased a coevolutionary race between the human immune system and SARS-CoV-2, during which the immune system generated neutralizing antibodies targeting the SARS-CoV-2 spike protein's receptor-binding domain (RBD), …
View article: Generation of antigen-specific paired chain antibody sequences using large language models
Generation of antigen-specific paired chain antibody sequences using large language models Open
The traditional process of antibody discovery is limited by inefficiency, high costs, and low success rates. Recent approaches employing artificial intelligence (AI) have been developed to optimize existing antibodies and generate antibody…
View article: Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families
Isolation and characterization of IgG3 glycan-targeting antibodies with exceptional cross-reactivity for diverse viral families Open
Broadly reactive antibodies that target sequence-diverse antigens are of interest for vaccine design and monoclonal antibody therapeutic development because they can protect against multiple strains of a virus and provide a barrier to evol…
View article: Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques
Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques Open
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…
View article: Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2
Synthetic coevolution reveals adaptive mutational trajectories of neutralizing antibodies and SARS-CoV-2 Open
The Covid-19 pandemic showcases a coevolutionary race between the human immune system and SARS-CoV-2, mirroring the Red Queen hypothesis of evolutionary biology. The immune system generates neutralizing antibodies targeting the SARS-CoV-2 …
View article: Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques
Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques Open
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 combined monoclonal antibody (mAb) isolation with deep B cell receptor (BC…
View article: Humoral immune responses to the monovalent XBB.1.5-adapted BNT162b2 mRNA booster
Humoral immune responses to the monovalent XBB.1.5-adapted BNT162b2 mRNA booster Open
Continued SARS-CoV-2 evolution and immune escape necessitated the development of updated vaccines, and a monovalent vaccine incorporating the XBB.1.5 variant spike protein is currently being rolled out. Amidst the emergence of the highly m…
View article: SARS-CoV-2 antibodies from children exhibit broad neutralization and belong to adult public clonotypes
SARS-CoV-2 antibodies from children exhibit broad neutralization and belong to adult public clonotypes Open
From the beginning of the COVID-19 pandemic, children have exhibited different susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, reinfection, and disease compared with adults. Motivated by the establ…
View article: Antigen receptor stimulation induces purifying selection against pathogenic mitochondrial tRNA mutations
Antigen receptor stimulation induces purifying selection against pathogenic mitochondrial tRNA mutations Open
Pathogenic mutations in mitochondrial (mt) tRNA genes that compromise oxidative phosphorylation (OXPHOS) exhibit heteroplasmy and cause a range of multisyndromic conditions. Although mitochondrial disease patients are known to suffer from …
View article: Sensitivity of BA.2.86 to prevailing neutralising antibody responses
Sensitivity of BA.2.86 to prevailing neutralising antibody responses Open
A new SARS-CoV-2 variant, designated BA.2.86, has recently emerged with over 30 spike mutations relative to its parental BA.2, raising questions about its degree of resistance to neutralising antibodies. Using a spike-pseudotyped virus mod…
View article: Frequent use of IGHV3-30-3 in SARS-CoV-2 neutralizing antibody responses
Frequent use of IGHV3-30-3 in SARS-CoV-2 neutralizing antibody responses Open
The antibody response to SARS-CoV-2 shows biased immunoglobulin heavy chain variable (IGHV) gene usage, allowing definition of genetic signatures for some classes of neutralizing antibodies. We investigated IGHV gene usage frequencies by s…
View article: Vaccine-induced correlate of protection against fatal COVID-19 in the old and frail during waves of neutralization resistant variants of concern
Vaccine-induced correlate of protection against fatal COVID-19 in the old and frail during waves of neutralization resistant variants of concern Open
Background To inform future preventive measures including repeated vaccinations, we have searched for a clinically useful immune correlate of protection against fatal Covid-19 among nursing homes residents. Methods We performed repeated ca…
View article: SARS-CoV-2 spike HexaPro formulated in aluminium hydroxide and administered in an accelerated vaccination schedule partially protects Syrian Hamsters against viral challenge despite low neutralizing antibody responses
SARS-CoV-2 spike HexaPro formulated in aluminium hydroxide and administered in an accelerated vaccination schedule partially protects Syrian Hamsters against viral challenge despite low neutralizing antibody responses Open
SARS-CoV-2 continues to pose a threat to human health as new variants emerge and thus a diverse vaccine pipeline is needed. We evaluated SARS-CoV-2 HexaPro spike protein formulated in Alhydrogel ® (aluminium oxyhydroxide) in Syrian hamster…
View article: Silver nanoparticles with excellent biocompatibility block pseudotyped SARS-CoV-2 in the presence of lung surfactant
Silver nanoparticles with excellent biocompatibility block pseudotyped SARS-CoV-2 in the presence of lung surfactant Open
Silver (Ag) is known to possess antimicrobial properties which is commonly attributed to soluble Ag ions. Here, we showed that Ag nanoparticles (NPs) potently inhibited SARS-CoV-2 infection using two different pseudovirus neutralization as…
View article: Longitudinal single-cell analysis of SARS-CoV-2–reactive B cells uncovers persistence of early-formed, antigen-specific clones
Longitudinal single-cell analysis of SARS-CoV-2–reactive B cells uncovers persistence of early-formed, antigen-specific clones Open
Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from pat…
View article: Vaccination of SARS-CoV-2-infected individuals expands a broad range of clonally diverse affinity-matured B cell lineages
Vaccination of SARS-CoV-2-infected individuals expands a broad range of clonally diverse affinity-matured B cell lineages Open
Vaccination of SARS-CoV-2 convalescent individuals generates broad and potent antibody responses. Here, we isolated 459 spike-specific monoclonal antibodies (mAbs) from two individuals who were infected with an early ancestral strain of SA…
View article: Omicron sublineage BA.2.75.2 exhibits extensive escape from neutralising antibodies
Omicron sublineage BA.2.75.2 exhibits extensive escape from neutralising antibodies Open
Several sublineages of omicron have emerged with additional mutations that may afford further antibody evasion. Here, we characterise the sensitivity of emerging omicron sublineages BA.2.75.2, BA.4.6, and BA.2.10.4 to antibody-mediated neu…
View article: Evasion of neutralizing antibodies by Omicron sublineage BA.2.75
Evasion of neutralizing antibodies by Omicron sublineage BA.2.75 Open
An emerging SARS-CoV-2 Omicron sublineage, BA.2.75, is increasing in frequency in India and has been detected in at least 15 countries as of 19 July 2022. Relative to BA.2, BA.2.75 carries nine additional mutations in spike. Here we report…
View article: HIV Coinfection Provides Insights for the Design of Vaccine Cocktails to Elicit Broadly Neutralizing Antibodies
HIV Coinfection Provides Insights for the Design of Vaccine Cocktails to Elicit Broadly Neutralizing Antibodies Open
Despite being the focus of extensive research, we still do not know how to reproducibly elicit cross-neutralizing antibodies against variable pathogens by vaccination. Here, we characterize the antibody responses in people coinfected with …