Latest publication

J Antimicrob Chemother. 2026 Sep 1;81(10):dkag300. doi: 10.1093/jac/dkag300.

ABSTRACT

BACKGROUND: Dolutegravir (DTG)-based antiretroviral therapy has been widely adopted across sub-Saharan Africa, yet resistance pathways in non-B HIV-1 subtypes remain poorly defined. As lenacapavir (LEN), a long-acting capsid inhibitor, is introduced for prevention and treatment, characterizing baseline capsid variation alongside emerging integrase resistance is increasingly important. Whether DTG resistance pathways coexist with known capsid resistance mutations in West African epidemics remains poorly described.

METHODS: We performed deep sequencing of 87 HIV-1 samples from adults (n = 47) and paediatric participants (n = 40) failing DTG-based antiretroviral therapy in Nigeria. Resistance mutations were interpreted using Stanford HIVdb and IAS-USA criteria, with resistance estimates based on gene- or drug-panel-specific denominators. Low-frequency variants were assessed at 2%, 5%, 10% and 20% read-frequency thresholds. Capsid mutations associated with LEN resistance were characterized, structurally mapped and compared to global sequence data. HIV-1 subtype and recombinant forms were assigned using COMET HIV-1 v2.4.

RESULTS: At consensus, predicted resistance to ≥1 integrase strand transfer inhibitor (INSTI) was detected in 13/50 integrase-genotypable participants (26.0%; 95% CI 15.9%-39.6%), including 5/50 with a major INSTI resistance mutation. Reduced predicted susceptibility specifically to DTG was present in 6/50 (12.0%; 95% CI 5.6%-23.8%). G118R was detected in 4/50 participants at consensus, while Q148H/K/R and N155H were absent. In exploratory deep-sequencing analysis, G118R was detected in 8/47 participants with sufficient codon-level coverage at the ≥20% read-frequency threshold. No known primary LEN resistance mutation was detected among 33 participants with complete coverage of all six primary resistance positions (0/33; 95% CI 0%-10.4%); T107A, a polymorphic capsid substitution of uncertain effect on LEN susceptibility, was detected in in 3/33 individuals where sequence could be evaluated.

CONCLUSIONS: These findings demonstrate DTG resistance in both adult and paediatric participants with virological failure with G118R emerging as a prominent resistance pathway. No known primary LEN resistance mutation was detected in the assessable capsid sequences, although phenotypic susceptibility and clinical outcomes were not evaluated. These findings support continued surveillance of integrase and capsid resistance as long-acting antiretroviral strategies expand.

PMID:42708709 | DOI:10.1093/jac/dkag300

Vaccine. 2026 Sep 7;92:129129. doi: 10.1016/j.vaccine.2026.129129. Online ahead of print.

ABSTRACT

Schistosomiasis (bilharzia) is a neglected tropical disease caused by Schistosoma spp. Clinical manifestation of chronic schistosomiasis include but not restricted to anemia, growth stunting, hepatosplenomegaly, cognitive impairment in children and male/female genital schistosomiasis. Praziquantel (PZQ) remains the principal standard treatment for schistosomiasis, but concerns about its reduced effectiveness against larval stages, reinfections, and emerging drug resistance reinforces the urgent need for a vaccine. SchistoShield®, composed of Sm-p80 antigen with GLA-SE adjuvant, is a promising vaccine candidate that has successfully completed phase 1 and 1b clinical trials in the USA and two countries in Africa (Madagascar and Burkina Faso). In this study, SchistoShield® vaccine specific total IgG antibody titers were measured from serum samples collected at multiple time points from both the USA and Africa trials. Results demonstrate that total IgG titers increased at week 5 after the first booster and peaked at weeks 9 and 12. Furthermore, in vitro schistosomula killing assays and heterologous passive transfer of purified total IgG in mice were performed to evaluate the role of vaccine-induced antibodies against schistosomes. Sera collected from individuals enrolled in the USA, Burkina Faso, and Madagascar trials, exhibited 69.2%, 55.1%, and 34.3% in vitro schistosomula killing, respectively, indicative of potent anti-worm antibody responses. Passive transfer of human total IgG from vaccinated individuals in mice revealed notable reductions in worm burden, egg counts, and egg-hatching ability compared to groups given pre-vaccination sera across all trials. Overall, these findings support that SchistoShield® induces generation of functional antibodies that may play a crucial role in antibody-mediated protection against schistosomiasis.

PMID:42705169 | DOI:10.1016/j.vaccine.2026.129129

Genes Immun. 2026 Aug 26. doi: 10.1038/s41435-026-00408-z. Online ahead of print.

ABSTRACT

Antibodies are the principal effector proteins of humoral immunity. Dysregulated antibody production is a feature of a number of heritable immune-mediated diseases, such as the antibody deficiencies and IgA nephropathy. To characterize the common-variant architecture of serum antibody levels in the general population, we conducted the largest GWAS meta-analyses to date of serum IgA, IgM and IgG, attaining sample sizes of 85,204, 55,368 and 58,777, respectively. We identified 82 novel associations across three isotypes, including 38 novel IgA associations (of a total of 77), 36 novel IgM associations (of a total of 82) and 8 novel IgG associations (of a total of 14). We found that isotype-specific genetic architecture was largely disjoint, with few signals colocalising across isotypes in spite of their overall positive genetic correlation. We identified a large number of colocalisations between antibody phenotypes and immune-mediated diseases and 16 between antibody phenotypes and a lymphocyte count phenotype. We report a greatly expanded catalogue of serum antibody-associated variants and characterise these in terms of their pathway context and relation to immune pathology.

PMID:42642615 | DOI:10.1038/s41435-026-00408-z

J Hum Immun. 2026 Aug 10;2(5):e20250175. doi: 10.70962/jhi.20250175. eCollection 2026 Sep 7.

ABSTRACT

Within a prospective cohort of patients with immune dysregulation, we identified several individuals with chronically increased proportions of TCR γδ cells but normal peripheral lymphocyte counts. Among those, we identified one individual with a TCR γδ cell-specific heterozygous p.Y665F STAT5B gain-of-function mutation. Recurrent oral aphthous lesions, susceptibility to infection, arthralgia, and fatigue, were linked to relatively elevated numbers of γδ T cells expressing a Vγ9Vδ2 TCR, displaying hyperphosphorylation of STAT5 upon in vitro IL-2 stimulation. The TCR Vγ9Vδ2 cells exhibited enhanced proliferative response to (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate and dysregulated cytokine production. The TCR γδ cell transcriptome revealed the suppression of the default Th17 program, along with inhibition of RORC and MAF expression. The JAK inhibitor baricitinib improved clinical features of the observed immune dysregulation and reduced the frequency of peripheral TCR Vγ9Vδ2 cells. Thus, functionally altered TCR γδ cells may underlie chronic immune dysregulation of unknown molecular cause, demonstrated here to be amenable to tailored immune modulation.

PMID:42577896 | PMC:PMC13455652 | DOI:10.70962/jhi.20250175

Nat Genet. 2026 Aug 4. doi: 10.1038/s41588-026-02681-0. Online ahead of print.

ABSTRACT

Innate lymphoid cells (ILCs) are rare tissue-resident lymphocytes that functionally mirror cells of CD4+ T helper lineage but lack antigen receptors. Type 3 ILCs (ILC3s) are enriched at barrier sites, regulating inflammation and promoting tissue integrity. Here we profile the promoter-anchored chromosomal contacts of primary human ILC3s using low-input, high-resolution targeted chromosome conformation capture and compare them with those in CD4+ T cells. We use these data to link Crohn's disease genome-wide association study variants with target genes, implicating both known and unanticipated candidates, including CLN3, a causal gene for Batten disease. We show that Cln3 overexpression in a mouse ILC3-like cell line alters stimulation-induced transcriptional programs and cytokine secretion. Extending our approach to five additional immune genome-wide association study traits reveals enrichment for regulators of ILC3 activation. Our work develops methods, maps long-range gene regulation in ILC3s, and prioritizes immune disease risk genes with roles in this clinically relevant immune cell type.

PMID:42552386 | DOI:10.1038/s41588-026-02681-0

FEBS Lett. 2026 Aug 1. doi: 10.1002/1873-3468.70423. Online ahead of print.

ABSTRACT

G protein-coupled receptor 35 (GPR35) has been implicated in cancer, but the functional roles of its isoforms remain unresolved. Here, we characterize GPR35-long, an N-terminally extended epithelial isoform selectively enriched in colorectal cancer and cholangiocarcinoma. Mass spectrometry and immunohistochemistry confirmed GPR35-long protein expression in tumor cells. Functional analyses revealed that GPR35-long supports tumor-associated transcriptional programs, enhances cellular ATP production, and exhibits increased constitutive and ligand-induced beta-arrestin signaling. These phenotypes were selectively suppressed by the inverse agonist CID-2745687, identifying GPR35-long as a functionally distinct isoform with selective pharmacological sensitivity in tumor cells.

PMID:42541411 | DOI:10.1002/1873-3468.70423

Ann Intern Med. 2026 Jul 21. doi: 10.7326/ANNALS-25-02412. Online ahead of print.

ABSTRACT

Prevalence and incidence are fundamental metrics with numerous applications in epidemiology. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline lacks specific items for reporting studies of disease prevalence or incidence. To address this gap, the STROBE Enhanced Prevalence and Incidence Criteria (STROBE EPIC) extension was developed in accordance with established methods for reporting guideline development. The authors generated an initial list of reporting items, conducted a modified Delphi process, and convened a face-to-face consensus meeting to confirm the need for a STROBE extension and to generate an early version of the checklist. They conducted 2 further Delphi surveys, first extending from typhoid and other invasive salmonelloses to all infectious diseases, and then to noncommunicable diseases and injuries. Finally, experts piloted the checklist on relevant manuscripts to critically assess if it was clear, concise, complete, and free of errors. An executive group curated the checklist after every survey round. The STROBE EPIC checklist comprises 47 items in the domains of title (1 item), abstract (2 items), introduction (1 item), methods (25 items), results (6 items), discussion (7 items), and other information (5 items). STROBE EPIC items address reporting of study design, adjustment factors for underreporting and underdiagnosis, denominator population estimation, case ascertainment methods, factors producing artefactual changes to observed disease prevalence or incidence, limitations of incomplete surveillance coverage, generalizability of short-duration studies, and data availability. The authors anticipate that the STROBE EPIC extension will be used by researchers, authors, modelers, burden-of-disease researchers, peer reviewers, and journal editors to optimize the presentation of epidemiologic evidence to support diverse health policy decisions.

PMID:42475690 | DOI:10.7326/ANNALS-25-02412

Gut. 2026 Jul 16:gutjnl-2026-339056. doi: 10.1136/gutjnl-2026-339056. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Restoration of intestinal barrier integrity and function in inflammatory bowel disease (IBD) has been associated not only with a reduced burden of persistent symptoms but also with improved long-term outcomes, prompting growing interest in intestinal barrier healing as a potential new therapeutic target. To date, no clinical trials have specifically evaluated therapies aimed at restoring intestinal barrier function in IBD, and there is currently no consensus on how such trials should be designed or how the intestinal barrier should be assessed. The aim of this initiative was to develop consensus recommendations on the optimal design of clinical trials and the selection of tools to evaluate therapies targeting the intestinal barrier in IBD.

METHODS: A panel of 12 international specialists with recognised expertise in the intestinal barrier and/or IBD clinical trials evaluated statements developed from a systematic literature review. Statements were discussed and anonymously voted on using a modified Delphi methodology. Consensus was predefined as at least 75% agreement among participants. The study was conducted and reported in accordance with the Conducting and REporting of DElphi Studies framework.

RESULTS: Fourteen statements reached consensus and were approved. These statements addressed key aspects of clinical trial design, including the role of intestinal barrier assessment as an endpoint, timing of reassessment, protocol requirements and disease-specific considerations. Additional statements focused on the selection and standardisation of tools for intestinal barrier assessment, encompassing imaging-based techniques, functional permeability assays and endogenous biomarkers, as well as considerations for implementation and future research directions.

CONCLUSIONS: This international consensus provides a structured framework to guide the design of future clinical trials evaluating efficacies of therapies in restoring intestinal barrier integrity and/or function in IBD.

PMID:42463422 | DOI:10.1136/gutjnl-2026-339056

PLoS Negl Trop Dis. 2026 Jun 24;20(6):e0014457. doi: 10.1371/journal.pntd.0014457. Online ahead of print.

ABSTRACT

INTRODUCTION: Non-typhoidal Salmonella (NTS) bloodstream infections complicate Plasmodium falciparum (Pf) malaria infections in children under-five, but bacterial co-infections are often missed due to absence of microbiological diagnosis. We compared signs/symptoms and outcome of NTS bloodstream infection, severe Pf malaria and NTS-Pf malaria co-infections.

METHODS: In an area with high, stable Pf malaria transmission (Kongo Central, DR Congo), children (>28 days- <5 years) admitted to hospital with severe febrile illness were enrolled during 18 months (NCT04473768/NCT04850677). Data (in-hospital and 1-month post-discharge) were prospectively collected.

RESULTS: NTS bloodstream infections and severe Pf malaria were diagnosed in 12% (331/2682) and 52% (1389/2682) of enrolled children, respectively. NTS-Pf co-infections occurred in 10% (264/2682) of enrolled children, i.e., Pf malaria co-infected 80% (264/330) of NTS bloodstream infections and NTS co-infected 6% (78/1389) of severe Pf malaria. In children with recent Pf malaria (i.e., HRP2-antigen persistence with negative microscopy), NTS occurred in 32% (173/545), making recent malaria a major risk factor for NTS (OR=5.85, p < 0.001). Compared to severe Pf malaria, age under-two (OR=2.19), > 3 days of fever (OR=3.28) and acute malnutrition (OR=2.20-3.48) were risk factors for NTS (p < 0.001) and NTS cases more often had hypoglycemia, grunting, hepato-/splenomegaly, jaundice or altered consciousness, but overall clinical presentation was not discriminative. In-hospital NTS case fatality was high (24% versus 3% in severe Pf malaria), occurred within 2 days of admission in 64% of deaths, and was preceded by general danger/sepsis signs. NTS cases had slower fever resolution, more frequent in-hospital fever recurrence, longer hospital stays, and more post-discharge deaths (n = 4) than severe Pf malaria cases.

CONCLUSION: NTS and Pf malaria frequently co-infected children under-five. Severe Pf malaria and NTS bloodstream infections could not be distinguished clinically, but fatality rates were higher in NTS. Low thresholds for empirical NTS antibiotics and early danger sign recognition triggering sepsis care might improve outcome.

PMID:42341028 | DOI:10.1371/journal.pntd.0014457

Nat Commun. 2026 Jun 23;17(1):5312. doi: 10.1038/s41467-026-74190-x.

ABSTRACT

Pneumonia is the leading infectious disease killer worldwide and commonly requires admission to critical care. Despite its prevalence, the underpinning biology of severe pneumonia remains incompletely understood. Here we perform multifaceted assessments of bronchoalveolar transcriptome, cytokines, microbiology, and clinical features to biologically characterise a cohort of patients with suspected severe pneumonia. Our data implicate three lung-restricted transcriptionally defined severe pneumonia endotypes (termed 'Pneumotypes' (Pn)). All three Pneumotypes have comparable clinical presentations and severity of respiratory failure but experience divergent outcomes. Pn1, the most common, is characterised by low alveolar cytokines, expanded tolerogenic macrophages and epithelial damage. Pn3 is characterised by immature neutrophil infiltration, IL-6-STAT3 activation and longer duration of mechanical ventilation. Pn2 displays the fastest resolution, exhibiting a balanced immune response and epithelial-endothelial repair signatures. We identify and validate mechanistically distinct phenotypes in the lungs of patients with suspected pneumonia and acute lung injury, implicating targets for personalised therapy.

PMID:42337236 | DOI:10.1038/s41467-026-74190-x

EMBO J. 2026 Jun 3. doi: 10.1038/s44318-026-00825-w. Online ahead of print.

ABSTRACT

Interferons (IFN) are cytokines that regulate the expression of hundreds of genes during viral infections to generate a broadly antiviral environment in the stimulated cell. Antiviral breadth is provided by the concurrent expression of many individual IFN-stimulated genes (ISG), each encoding a protein with often exquisite antiviral specificity. Here, we identify mechanistic plasticity at a single genetic locus as a novel mechanism to diversify the antiviral profile of human cells. Through alternative splicing, the OAS2 gene encodes two antiviral molecules with distinct target specificities. The shorter OAS2 p69 isoform restricts seasonal human coronavirus OC43 (HCoV-OC43), whereas the longer p71 isoform restricts picornavirus Cardiovirus A (EMCV). The restriction profile is determined by the variable length OAS2 C-terminal tails. Notably, these antiviral activities differ in their dependence on RNase L, suggesting that alternative splicing separates canonical restriction and virus sensing functions across two distinct OAS2 polypeptides. Together, these findings show how alternative splicing expands antiviral diversity at the human OAS2 locus.

PMID:42236548 | DOI:10.1038/s44318-026-00825-w

NPJ Vaccines. 2026 Jun 2. doi: 10.1038/s41541-026-01501-0. Online ahead of print.

ABSTRACT

Helminth parasites of the genus Schistosoma cause 290,000 deaths annually, mostly in tropical and subtropical regions. An estimated 250 million people are currently chronically infected with Schistosoma parasites, imposing a risk of new and recurrent infections in an additional 800 million people. SchistoShield® (Sm-p80 + GLA-SE) is a leading vaccine candidate for schistosomiasis that has successfully completed Phase 1 (USA) and Phase 1b (Africa) safety and immunogenicity clinical trials. Using Peripheral Blood Mononuclear Cells (PBMCs) obtained from intercontinental Phase 1 and Phase 1b trial participants, adaptive immune effector and memory responses to SchistoShield® were investigated. Functional recall responses were measured in vitro using Sm-p80 vaccine antigen. Results clearly demonstrate that the vaccine induced pronounced effector and memory T-cell responses. Upon recall with Sm-p80 antigen, cytokines including IFN-γ, TNF-α, IL-17A, IL-9, and granzyme B were produced, indicating the generation of functionally heterogeneous CD4 T-helper and cytotoxic lymphocyte responses. Consistent with T-helper responses that promote humoral immunity, Sm-p80 antigen-specific antibody-secreting plasmablasts were detected in vaccinated volunteers who were tracked longitudinally. Taken together, the SchistoShield® vaccine induced robust cell-mediated effector and memory responses, hallmarks of a potentially efficacious vaccine against schistosome/helminth parasites.

PMID:42230670 | DOI:10.1038/s41541-026-01501-0

iScience. 2026 Apr 28;29(6):115910. doi: 10.1016/j.isci.2026.115910. eCollection 2026 Jun 19.

ABSTRACT

Distinct from vaccine-first models, infection-first exposures provide a critical context for understanding SARS-CoV-2 immune imprinting in unvaccinated populations. We analyzed neutralizing antibody responses in two independent unvaccinated Nigerian cohorts sampled in early 2023. Using a BA.1 receptor-binding domain (RBD)-based assay for Omicron exposure discrimination, we identified widespread pre-Omicron and partial Omicron exposure. Despite recent Omicron infection, plasma neutralization titers against Omicron lineages remained equal or lower compared to those against ancestral Wu-1, indicating infection-derived imprinting. Depletion of Wu-1 spike-binding antibodies abrogated neutralization of both Wu-1 and Omicron pseudoviruses, confirming dominance of ancestral cross-reactive antibodies. Following Wu-1-based vaccination, neutralizing responses increased across all variants, yet Omicron titers did not exceed Wu-1 titers even after breakthrough infection. These findings demonstrate durable infection-induced immune imprinting established before vaccination and only partially mitigated by repeated Omicron exposures, underscoring the influence of infection-first exposure sequence on antibody breadth and broader global relevance for vaccine design.

PMID:42221816 | PMC:PMC13218260 | DOI:10.1016/j.isci.2026.115910

Cell Rep. 2026 May 28;45(6):117460. doi: 10.1016/j.celrep.2026.117460. Online ahead of print.

ABSTRACT

Prolonged infections in immunocompromized individuals are associated with accumulation of unexpected combinations of mutations, as exemplified by the Omicron variant. Here, we show that intra-host evolution during a chronic SARS-CoV-2 infection in the pre-Omicron era was associated with mutations that modulate antibody evasion, cell entry efficiency, spike processing, and fusogenicity. Single spike N-terminal mutations S13I and W64G exerted deleterious impacts on S1/S2 cleavage, syncytia formation, and cell entry but combined through an inferred recombination event with P330S to restore function. The single mutants were never detected individually in respiratory samples, but mediated temperature-dependent evasion from neutralizing antibodies and altered reliance on TMPRSS2-mediated membrane fusion, possibly explaining their transient selection. Molecular dynamics simulations revealed that W64G induces local N-terminal domain destabilization with distal effects at the S1/S2 cleavage loop, linking structural perturbation to functional defects and immune evasion. Together, these findings demonstrate how intra-host recombination contributes to viral adaptation.

PMID:42213788 | DOI:10.1016/j.celrep.2026.117460

Clin Microbiol Infect. 2026 May 21:S1198-743X(26)00265-X. doi: 10.1016/j.cmi.2026.05.023. Online ahead of print.

NO ABSTRACT

PMID:42173193 | DOI:10.1016/j.cmi.2026.05.023