A case of disseminated autochthonous Cladophialophora bantiana infection in a renal transplant recipient in the UK.

Disease associated with Cladophialophora bantiana infection is uncommon but can be characterised by severe and life-threatening CNS involvement. Diagnosis is challenging due to both the infection's rarity and non-specific clinical presentation, which can mimic malignancy and infection caused by more common organisms. Transmission can occur via inhalation or inoculation through compromised skin, followed by haematogenous dissemination to the brain and other organs.

Letter to the Editor: Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection.

Research into HLA-B*15:01 association with asymptomatic SARS-CoV-2 infection has so far yielded contradicting results. Using the UK Biobank cohort, we found a significant association between HLA-B*15:01 and asymptomatic infection. Our study adds more evidence for the complex role HLA alleles play in SARS-Cov-2 infection severity.

Novel risk loci in LGI1-antibody encephalitis: genome-wide association study discovery and validation cohorts.

Encephalitis with antibodies to leucine-rich glioma-inactivated 1 (LGI1-Ab-E) is a common form of autoimmune encephalitis, presenting with seizures and neuropsychiatric changes, predominantly in older males. More than 90% of patients carry the human leucocyte antigen (HLA) class II allele, HLA-DRB1*07:01. However, this is also present in 25% of healthy controls.

Genetic Signatures of Positive Selection in Human Populations Adapted to High Altitude in Papua New Guinea.

Papua New Guinea (PNG) hosts distinct environments mainly represented by the ecoregions of the Highlands and Lowlands that display increased altitude and a predominance of pathogens, respectively. Since its initial peopling approximately 50,000 years ago, inhabitants of these ecoregions might have differentially adapted to the environmental pressures exerted by each of them. However, the genetic basis of adaptation in populations from these areas remains understudied.

A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity.

BA.2.86, a recently described sublineage of SARS-CoV-2 Omicron, contains many mutations in the spike gene.

How could our genetics impact COVID-19 vaccine response?

Introduction: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed unprecedented global health challenges since its emergence in December 2019. The rapid availability of vaccines has been estimated to save millions of lives, but there is variation in how individuals respond to vaccines, influencing their effectiveness at an individual, and population level.

Areas Covered: This review focuses on human genetic factors influencing the immune response and effectiveness of vaccines, highlighting the importance of associations across the HLA locus.

Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection.

The rapid evolution of SARS-CoV-2 is driven in part by a need to evade the antibody response in the face of high levels of immunity. Here, we isolate spike (S) binding monoclonal antibodies (mAbs) from vaccinees who suffered vaccine break-through infections with Omicron sub lineages BA.4 or BA.

The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86.

Under pressure from neutralising antibodies induced by vaccination or infection the SARS-CoV-2 spike gene has become a hotspot for evolutionary change, leading to the failure of all mAbs developed for clinical use. Most potent antibodies bind to the receptor binding domain which has become heavily mutated. Here we study responses to a conserved epitope in sub-domain-1 (SD1) of spike which have become more prominent because of mutational escape from antibodies directed to the receptor binding domain.

Genetic Susceptibility to Astrovirus Diarrhea in Bangladeshi Infants.

Background: Astroviral infections commonly cause acute nonbacterial gastroenteritis in children globally. However, these infections often go undiagnosed outside of research settings. There is no treatment available for astrovirus, and Astroviridae strain diversity presents a challenge to potential vaccine development.

Advancing multiplex serology.

Unlabelled: is a highly prevalent pathogen causing zoonotic infections with significant public health implications. Yet, our understanding of long-term consequences, associated risk factors, and the potential role of co-infections is still limited. Seroepidemiological studies are a valuable approach to address open questions and enhance our insights into across human populations.

A common NFKB1 variant detected through antibody analysis in UK Biobank predicts risk of infection and allergy.

Infectious agents contribute significantly to the global burden of diseases through both acute infection and their chronic sequelae. We leveraged the UK Biobank to identify genetic loci that influence humoral immune response to multiple infections. From 45 genome-wide association studies in 9,611 participants from UK Biobank, we identified NFKB1 as a locus associated with quantitative antibody responses to multiple pathogens, including those from the herpes, retro-, and polyoma-virus families.

N-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting.

In vitro-transcribed (IVT) mRNAs are modalities that can combat human disease, exemplified by their use as vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IVT mRNAs are transfected into target cells, where they are translated into recombinant protein, and the biological activity or immunogenicity of the encoded protein exerts an intended therapeutic effect. Modified ribonucleotides are commonly incorporated into therapeutic IVT mRNAs to decrease their innate immunogenicity, but their effects on mRNA translation fidelity have not been fully explored.

Mexican Biobank advances population and medical genomics of diverse ancestries.

Latin America continues to be severely underrepresented in genomics research, and fine-scale genetic histories and complex trait architectures remain hidden owing to insufficient data. To fill this gap, the Mexican Biobank project genotyped 6,057 individuals from 898 rural and urban localities across all 32 states in Mexico at a resolution of 1.8 million genome-wide markers with linked complex trait and disease information creating a valuable nationwide genotype-phenotype database.

Topic modeling identifies novel genetic loci associated with multimorbidities in UK Biobank.

Many diseases show patterns of co-occurrence, possibly driven by systemic dysregulation of underlying processes affecting multiple traits. We have developed a method (treeLFA) for identifying such multimorbidities from routine health-care data, which combines topic modeling with an informative prior derived from medical ontology. We apply treeLFA to UK Biobank data and identify a variety of topics representing multimorbidity clusters, including a healthy topic.

Targeting hepatitis B vaccine escape using immunogenetics in Bangladeshi infants.

Hepatitis B virus (HBV) vaccine escape mutants (VEM) are increasingly described, threatening progress in control of this virus worldwide. Here we studied the relationship between host genetic variation, vaccine immunogenicity and viral sequences implicating VEM emergence. In a cohort of 1,096 Bangladeshi children, we identified human leukocyte antigen (HLA) variants associated with response vaccine antigens.

HLA-E-restricted SARS-CoV-2-specific T cells from convalescent COVID-19 patients suppress virus replication despite HLA class Ia down-regulation.

Pathogen-specific CD8 T cell responses restricted by the nonpolymorphic nonclassical class Ib molecule human leukocyte antigen E (HLA-E) are rarely reported in viral infections. The natural HLA-E ligand is a signal peptide derived from classical class Ia HLA molecules that interact with the NKG2/CD94 receptors to regulate natural killer cell functions, but pathogen-derived peptides can also be presented by HLA-E. Here, we describe five peptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that elicited HLA-E-restricted CD8 T cell responses in convalescent patients with coronavirus disease 2019.

Large clones of pre-existing T cells drive early immunity against SARS-COV-2 and LCMV infection.

T cell responses precede antibody and may provide early control of infection. We analyzed the clonal basis of this rapid response following SARS-COV-2 infection. We applied T cell receptor (TCR) sequencing to define the trajectories of individual T cell clones immediately.

Evaluation of T cell responses to naturally processed variant SARS-CoV-2 spike antigens in individuals following infection or vaccination.

Most existing studies characterizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses are peptide based. This does not allow evaluation of whether tested peptides are processed and presented canonically. In this study, we use recombinant vaccinia virus (rVACV)-mediated expression of SARS-CoV-2 spike protein and SARS-CoV-2 infection of angiotensin-converting enzyme (ACE)-2-transduced B cell lines to evaluate overall T cell responses in a small cohort of recovered COVID-19 patients and uninfected donors vaccinated with ChAdOx1 nCoV-19.

Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis.

Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed that neutrophils and emergency granulopoiesis drove a maladaptive response during sepsis. We generated a whole-blood single-cell multiomic atlas (272,993 cells, n = 39 individuals) of the sepsis immune response that identified populations of immunosuppressive mature and immature neutrophils.

Rapid escape of new SARS-CoV-2 Omicron variants from BA.2-directed antibody responses.

In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.

Variation in ERAP2 has opposing effects on severe respiratory infection and autoimmune disease.

ERAP2 is an aminopeptidase involved in immunological antigen presentation. Genotype data in human samples from before and after the Black Death, an epidemic due to Yersinia pestis, have marked changes in allele frequency of the single-nucleotide polymorphism (SNP) rs2549794, with the T allele suggested to be deleterious during this period, while ERAP2 is also implicated in autoimmune diseases. This study explored the association between variation at ERAP2 and (1) infection, (2) autoimmune disease, and (3) parental longevity.