The study, conducted between March and September 2023, recruited convalescent individuals across Fuzhou and assessed them at baseline, Month 3, and Month 6. Serum IgG concentrations targeting SARS-CoV-2 were quantified using a chemiluminescence immunoassay, a platform widely used in clinical serology because of its high sensitivity and throughput. Rather than treating each measurement as an isolated snapshot, the investigators applied linear mixed-effects models to the longitudinal data, a statistical framework that allows each participant to serve, in effect, as their own control while accounting for repeated measurements nested within individuals. Because antibody titers are typically right-skewed, the team used a Yeo–Johnson transformation, a flexible power transformation that can accommodate both positive and negative values and stabilizes variance across a wide dynamic range, improving the validity of the mixed-model estimates.

One of the methodological challenges inherent to any longitudinal cohort is attrition: not every participant returns for every scheduled blood draw, and simply discarding incomplete records can bias results if dropouts differ systematically from those who complete follow-up. The Fuzhou team addressed this with multiple imputation, generating plausible values for missing follow-up IgG measurements based on the observed data structure and incorporating the uncertainty of those imputations into the final estimates. This approach preserves statistical power and reduces the risk that the apparent shape of antibody waning is an artifact of who happened to show up for their third visit. It is the kind of unglamorous but essential statistical hygiene that determines whether a cohort study’s conclusions can be trusted.

The central finding is that IgG trajectories diverged sharply by age group. Participants aged 0 to 18 years entered the study with higher baseline IgG levels than older participants, yet they experienced a more pronounced overall decline across the follow-up period. In other words, children and adolescents mounted robust antibody responses after infection but shed them relatively quickly. At the opposite end of the age spectrum, adults aged 65 and older showed no significant change in IgG from baseline to Month 3, followed by a subsequent decrease. This pattern suggests a relatively stable early phase of antibody persistence in older adults, with waning emerging later in the observation window, a tempo that is nearly the mirror image of what the youngest participants displayed.

The immunological logic behind such age-dependent divergence is a matter of active investigation. Younger immune systems generally generate vigorous germinal center reactions and produce high titers of neutralizing antibody after infection or vaccination, but those titers contract rapidly once the acute response subsides, leaving behind a smaller pool of long-lived plasma cells. Older adults, by contrast, often start from a lower peak but may exhibit slower contraction of the antibody compartment, although their overall humoral reserve is diminished and their protection against reinfection can be more fragile. The Fuzhou data cannot disentangle these mechanisms directly, since the study measured circulating IgG concentrations rather than memory B cell dynamics, but the trajectories are consistent with the broader literature on immune system aging, or immunosenescence, and with prior observations that antibody decay curves after SARS-CoV-2 infection are not uniform across populations.

Beyond age, the study identified several factors independently associated with IgG levels. Sex, notably, was not one of them; men and women showed no meaningful difference in antibody concentrations once other variables were accounted for. Symptom status, however, mattered. Asymptomatic individuals had lower IgG levels than those who had experienced symptomatic infection with recovery within one week, a finding that aligns with the well-established relationship between antigen load and the magnitude of the adaptive response. A symptomatic infection typically involves higher viral burden and more sustained antigenic stimulation, driving a stronger and more durable antibody output, whereas an asymptomatic or minimally symptomatic infection may fail to fully engage the germinal center machinery that produces high-affinity, long-lived antibody-secreting cells.

Vaccination history and smoking also left their fingerprints on the antibody curves. Participants with recent vaccination had higher IgG levels than those without, an expected but important confirmation that vaccine-boosted humoral immunity remains measurable in convalescent populations even months after infection. This hybrid immunity, the combination of vaccine-primed and infection-elicited responses, is now recognized as producing the most durable antibody profiles against SARS-CoV-2. Smoking history, on the other hand, was associated with lower IgG levels, adding to a growing body of evidence that cigarette smoke alters respiratory mucosal immunity and systemic inflammatory states in ways that can blunt or reshape antibody responses. The authors also observed inter-district heterogeneity in IgG levels across Fuzhou, meaning that where participants lived was associated with measurable differences in antibody concentrations. The study did not determine the cause of this geographic variation, and the authors note that it warrants further investigation; plausible explanations could include differences in local vaccination uptake, prior exposure intensity, or demographic composition, but the data available do not settle the question.

Technically, the study’s design choices deserve attention from readers who follow seroepidemiology. The chemiluminescence immunoassay used provides quantitative IgG values rather than simple positive-or-negative calls, which is what makes trajectory modeling possible in the first place. The Yeo–Johnson transformation is a thoughtful choice over the more common log transformation because it does not require strictly positive values, giving the modelers more flexibility when handling the full distribution of titers. Linear mixed-effects models with random intercepts and slopes allow the estimation of both average population-level decline and individual-level variation around that average, and the inclusion of fixed effects for age group, sex, symptom status, vaccination, smoking, and district permits simultaneous adjustment for potential confounders. Multiple imputation, when properly specified, is preferable to complete-case analysis in cohorts with uneven follow-up. Together, these methods produce estimates that are more robust than the simple before-and-after comparisons that dominated early pandemic serology.

The public health implications of the findings are straightforward even if the mechanisms remain open. If antibody persistence genuinely differs by age, then blanket assumptions about population-level immunity, the kind that feed into booster scheduling and reinfection risk models, may misrepresent both the youngest and oldest segments of the population. Children with rapidly waning antibodies may become increasingly susceptible to reinfection between waves, while older adults, despite a stable early antibody phase, face the steepest consequences when that protection eventually erodes. The authors frame their results as supporting age-stratified longitudinal surveillance, and the recommendation is well taken: understanding who loses antibody protection and when is a prerequisite for rational booster policy, particularly as new variants continue to emerge and the antigenic distance from prior infection grows.

The study also carries the usual caveats that apply to observational cohort research. It was conducted in a single Chinese city over a six-month window in 2023, a period when the circulating variant landscape and vaccination coverage differed from earlier phases of the pandemic, so the absolute IgG levels and decay rates may not generalize directly to other populations or time points. The six-month follow-up captures only the early-to-intermediate phase of antibody waning, and longer observation will be needed to determine whether the age-related patterns persist, accelerate, or plateau. The inter-district differences, meanwhile, remain an intriguing but unexplained signal. Still, with 2,482 participants tracked across three time points and a modeling framework built to handle the messiness of real-world longitudinal data, the study provides a valuable reference point for the ongoing effort to map the durability of anti-SARS-CoV-2 immunity, and it reinforces a conclusion that has been accumulating across the field since 2020: antibody memory after this virus is not a single curve but a family of curves, shaped by age, exposure history, and the biology of the individual carrying them.

Subject of Research: Longitudinal dynamics of SARS-CoV-2 IgG antibodies in convalescent individuals across age groups

Article Title: SARS-CoV-2 IgG antibody and associated factors in a large longitudinal cohort of convalescent individuals

Article References: Wang, X., Liang, Z., Peng, H., Yang, X., Zhang, C., Chen, Z., & Zhang, X. (2026). SARS-CoV-2 IgG antibody and associated factors in a large longitudinal cohort of convalescent individuals. Virology Journal. https://doi.org/10.1186/s12985-026-03328-6

Image Credits: AI Generated

DOI: 10.1186/s12985-026-03328-6

Keywords: SARS-CoV-2, IgG antibodies, antibody dynamics, longitudinal cohort, humoral immunity, age-specific dynamics, seroepidemiology, vaccination, smoking, asymptomatic infection, immunosenescence, Virology Journal

Weaning is a physiological crucible for goat kids. Abrupt separation from the dam, a sudden shift from milk to solid feed, and an immature rumen converge to create a window of heightened susceptibility to gastrointestinal and respiratory disease. Pre-weaning mortality remains a persistent problem in goat production systems worldwide, and producers have long sought alternatives to prophylactic antibiotics, whose use is increasingly restricted on animal welfare and antimicrobial resistance grounds. Astragalus membranaceus, known in Chinese pharmacopoeia as huangqi, has been used for centuries as an immunomodulatory tonic, and a substantial body of modern research attributes much of its bioactivity to polysaccharides that can influence dendritic cells, macrophages, and B lymphocyte function. What has been missing, however, is a rigorous, molecularly informed assessment of how the herb affects the peripheral immune system of young ruminants specifically.

The research team addressed that gap with a controlled feeding trial involving thirty-six black Xiangdong goat kids, all weaned at postnatal day 42 and weighing on average about 5.3 kilograms. The animals were randomly divided into two groups: a control group of sixteen kids receiving only a basal diet, and a treatment group of twenty kids receiving the basal diet supplemented with ten grams per day of ultrafine-grained Astragalus membranaceus powder, abbreviated UGAM. After an eight-day adaptation period, the supplementation phase ran from postnatal day 43 through day 78, giving the treatment roughly five full weeks of exposure. The choice of ultrafine grinding was deliberate. By reducing particle size dramatically, ultrafine processing increases the surface area available for digestion and absorption, potentially liberating more of the herb’s active polysaccharides and other constituents than conventional coarse powders would allow.

On day 78, the researchers drew blood from every animal and subjected the samples to a battery of immunological assays. They quantified seven complement proteins spanning the classical and regulatory arms of the cascade, C1q, C1r, C1s, C3, C4, C4bp, and Factor H, together with the three major immunoglobulin classes, IgA, IgG, and IgM, and a panel of six inflammatory cytokines including IL-1α, IL-1β, IL-6, IL-10, TNF-α, and IFN-γ. Complete peripheral blood cell profiles rounded out the picture. In a randomly selected subset of eleven control animals and sixteen treated animals, the team also measured hepatic expression of complement-related genes using reverse transcription quantitative PCR, capitalizing on the fact that the liver is the principal site of complement protein synthesis and an increasingly recognized hub of systemic innate immunity.

The results were strikingly specific. Serum concentrations of C4bp, a glycoprotein that acts as a major negative regulator of the classical and lectin complement pathways by accelerating the decay of C3 and C5 convertases and serving as a cofactor for Factor I-mediated cleavage of C4b, rose significantly in the treated animals. Crucially, this increase was mirrored at the transcript level: hepatic C4bp mRNA expression was also significantly elevated, with the serum protein and liver gene expression changes both reaching statistical significance at p less than 0.001. This concordance between circulating protein and hepatic messenger RNA suggests that the herb acts, at least in part, by transcriptionally upregulating complement regulatory machinery in the liver rather than merely altering protein clearance or distribution. Alongside the C4bp signal, the treated kids showed significantly higher circulating IgM, the phylogenetically oldest and first-response antibody class, produced early in immune responses by naive B cells.

Equally informative was what did not change. Levels of IgA and IgG, the other two immunoglobulin classes measured, remained statistically indistinguishable between the groups, as did all six inflammatory cytokines. This absence of cytokine elevation is arguably as important as the increases themselves. Many immunostimulatory feed additives work, when they work, by provoking a mild inflammatory response, which carries metabolic costs and risks of tissue damage if sustained. The UGAM-treated animals instead exhibited a pattern consistent with homeostatic tuning: an expanded complement regulatory capacity and a bolstered first-line humoral defense, achieved without activating pro-inflammatory or even broadly anti-inflammatory cytokine programs. The researchers interpreted this as evidence of engagement of the body’s homeostatic complement regulatory system rather than blunt immune activation.

To test whether the observed changes were genuinely linked to the treatment rather than artifacts of multiple comparisons, the team employed a multi-parameter statistical framework. In that analysis, UGAM supplementation emerged as independently and positively associated with C4bp levels, with a partial correlation coefficient of 0.74 and a p-value below 0.001, a robust effect size for a nutritional intervention in a livestock trial. Furthermore, a Mantel test comparing the overall correlation structures of the complement system and the immunoglobulin panel revealed significant concordance between the two modules, with a Mantel statistic of 0.36 and p equal to 0.001. This suggests that the complement and antibody arms of humoral immunity moved together in response to the intervention, consistent with the well-documented crosstalk between complement activation products and B cell responses, in which complement receptor engagement shapes antibody quality and magnitude.

The study builds on a growing literature exploring Astragalus preparations across livestock species. Previous work has documented improved growth performance, serum immunity, and antioxidant status in Tibetan sheep and finishing lambs supplemented with Astragalus root, enhanced intestinal health and gut microbiota profiles in broilers fed Astragalus-derived polysaccharides, and protective effects on mucosal immunity in immunosuppressed poultry. An earlier companion study by some of the same authors showed that ultra-ground Astragalus supplementation altered ileal microbiome composition and mucosal immune profiles in weaned goats, and the new work extends that picture to the systemic, liver-centered complement axis. Notably, several prior studies linked Astragalus polysaccharides to effects on NF-κB signaling and trained immunity pathways, providing plausible mechanistic scaffolding for the observed hepatic transcriptional changes, though the present study did not directly assay these signaling pathways.

The authors are appropriately measured about the limits of their evidence. Complement activity itself, as opposed to component concentrations, was not measured, and neither were plasma cell responses, downstream signaling events, or formal safety parameters, leaving the precise mechanisms behind the observed C4bp and IgM elevations hypothetical and requiring validation in future experiments. The treatment group was also larger than the control group, and hepatic gene expression was assessed in a subset rather than the full cohort. Nonetheless, the internal consistency of the findings, spanning protein, transcript, and multivariate correlation analyses, lends the central conclusion considerable weight. The trial was funded by China’s National Key Research and Development Program and the Natural Science Foundation of Guangxi, and the analysis code has been made publicly available on GitHub, an increasingly welcome transparency measure in animal science.

If replicated and extended, the implications extend beyond goat husbandry. The complement system sits at the intersection of innate and adaptive immunity, and pharmacological or nutritional modulation of its regulatory arm, particularly C4bp, is an active frontier in human medicine, with complement-targeting therapeutics advancing for conditions ranging from nephropathy to autoimmune disease. Demonstrating that a simple dietary herb powder can shift complement regulatory tone in a large animal model, without inflammatory side effects, offers a conceptual bridge between traditional herbal medicine and modern molecular immunology. For producers of black Xiangdong goats, a breed valued in subtropical China, the prospect of a ten-gram daily supplement that meaningfully supports humoral immunity through the perilous post-weaning weeks is an attractive one. The next step, the researchers indicate, will be to confirm the mechanisms, verify safety over longer durations, and determine whether the immunological gains translate into measurable improvements in disease resistance and survival under field conditions.

Subject of Research: Effects of oral ultrafine-grained Astragalus membranaceus supplementation on complement regulator C4bp and immunoglobulin responses in weaned goats

Article Title: Oral administration of ultrafine-grained Astragalus membranaceus enhances peripheral immunity in weaned black Xiangdong goats by upregulating the complement regulator C4bp and immunoglobulin responses

Article References: Liao, J., Sun, J., Gebeyew, K., Khan, N. A., & Liu, Y. (2026). Oral administration of ultrafine-grained Astragalus membranaceus enhances peripheral immunity in weaned black Xiangdong goats by upregulating the complement regulator C4bp and immunoglobulin responses. Molecular Biology Reports, 53(1), Article 1680. https://doi.org/10.1007/s11033-026-12883-8

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12883-8

Keywords: Astragalus membranaceus, complement system, C4bp, immunoglobulins, IgM, weaned goats, ultrafine grinding, hepatic gene expression, innate immunity, humoral immunity, livestock nutrition, Xiangdong goats

The EG95 protein has occupied a special place in echinococcosis research since its discovery as a protective antigen from oncosphere-stage parasites. Recombinant EG95-based vaccines have shown efficacy in sheep and have been deployed in some control programs, but the platform has persistent weaknesses. Protein subunit vaccines tend to elicit immune responses that wane relatively quickly, requiring booster doses and careful scheduling to maintain protection in flocks. Their production depends on expression systems that can be technically demanding, and the immunogenicity of the purified antigen, while real, is modest compared with what newer vaccine technologies can achieve. For a neglected zoonotic disease whose control depends on vaccinating large numbers of livestock in resource-limited settings, those limitations matter enormously.

The Chinese research group, whose members span institutions working on parasitic diseases and veterinary science, reasoned that the mRNA-lipid nanoparticle platform, which transformed human vaccinology during the COVID-19 pandemic, could address these shortcomings. mRNA vaccines instruct the recipient’s own cells to manufacture the target antigen, which means the protein is produced in its native form, with appropriate folding and post-translational modifications, and presented to the immune system in a context that engages both antibody and T-cell arms of immunity. The lipid nanoparticles that deliver the messenger RNA also act as built-in adjuvants, stimulating innate immune sensors that amplify the adaptive response. Manufacturing is fast, scalable, and does not require cell culture systems specific to each antigen, making the platform attractive for diseases that have never attracted the commercial investment of human medicine.

From this starting point, the team designed three vaccine candidates. The first was a straightforward EG95 mRNA-LNP vaccine, encoding the canonical protective antigen. The second, an IL-4-EG95 mRNA-LNP vaccine, was more inventive: it encoded a fusion protein in which EG95 was joined to interleukin-4, an immune signaling molecule, via a flexible peptide linker. The idea was to exploit the cytokine as a molecular adjuvant, tethering an immunostimulatory signal directly to the antigen so that cells taking up the vaccine would present EG95 in a context primed to enhance immune activation. The third candidate, an EG95-EC95 mRNA-LNP vaccine, took a multivalent approach, incorporating EC95 antigens derived from Echinococcus canadensis, a related parasite species within the E. granulosus sensu lato complex. Because the parasite species complex encompasses organisms with antigenic variation, a formulation that covers multiple variants could broaden protection across the range of parasites circulating in different regions and host species.

The researchers confirmed that all three vaccine candidates were efficiently encapsulated in lipid nanoparticles and that the encoded antigens were robustly expressed both in cell culture and in vaccinated animals. Expression of the target protein is the essential first step for any mRNA vaccine, and the fusion constructs, despite their added complexity, performed well. With the platform validated in vitro, the team moved to animal studies, comparing the mRNA vaccines head-to-head with a commercial EG95 subunit vaccine, the benchmark against which any new echinococcosis vaccine must be measured.

The immunological results were striking. In both mice and lambs, the mRNA-LNP vaccines induced humoral and cellular immune responses that were significantly stronger than those provoked by the subunit vaccine. Antibody titers rose higher and, critically, persisted longer: the animals maintained high levels of EG95-specific antibodies for more than twelve months after vaccination. For a livestock vaccine intended to protect animals through the period when they are most vulnerable to infection and through the breeding cycles of a working flock, that durability is a decisive advantage. It suggests that a vaccination schedule built on the mRNA platform could achieve with fewer doses what currently requires repeated boosters, reducing the logistical burden on herders and veterinary services in endemic regions.

Cellular immunity, often the neglected dimension in evaluations of antiparasitic vaccines, also differed markedly between the platforms. The mRNA vaccines engaged T-cell responses to a degree the subunit formulation did not match, a consequence of the way lipid nanoparticles deliver their cargo into cells and stimulate innate immune pathways. Because the immune response to Echinococcus involves both antibodies that attack oncospheres as they attempt to establish infection and cellular mechanisms that shape the environment around developing parasites, the breadth of the response induced by the mRNA platform may explain much of its protective superiority.

The decisive test came from parasite challenge experiments. When vaccinated animals were exposed to Echinococcus infection, the three mRNA-LNP vaccines all conferred protection, but the IL-4-EG95 fusion vaccine stood out. In animals receiving that formulation, the survival of protoscoleces, the larval forms that seed hydatid cysts, was inhibited, and the growth of cysts that did establish was suppressed. The fusion of the cytokine to the antigen, an approach that might have backfired by skewing immunity in an unhelpful direction, instead delivered the most effective protection of any candidate tested. The result validates the concept of genetically adjuvanted mRNA vaccines for parasitic diseases and suggests that the IL-4-EG95 construct is the leading candidate for further development.

The implications extend beyond echinococcosis itself. Cystic echinococcosis is one of many neglected zoonotic diseases for which the economics of vaccine development have never worked in favor of conventional platforms. The mRNA approach offers safety, scalability, and flexibility: the same lipid nanoparticle technology can be adapted to new antigens simply by changing the encoded sequence, and manufacturing does not depend on the biological quirks of expression systems. For a disease whose control requires coordinated vaccination of livestock, deworming of dogs, and public health surveillance across vast rural landscapes, a vaccine that is both more effective and longer-lasting could shift the calculus of elimination programs that have struggled for decades.

The study, published in PLOS Pathogens, positions EG95-based mRNA vaccines as a promising strategy for reducing the transmission of E. granulosus sensu lato and, with it, the zoonotic burden of cystic echinococcosis in the communities where the parasite remains endemic. Challenges remain before the platform reaches the field, including the regulatory pathways for veterinary mRNA vaccines, cold-chain requirements for lipid nanoparticle formulations, and the scale-up of challenge studies in livestock under natural transmission conditions. But the demonstration that mRNA vaccines can outperform the established subunit benchmark in both magnitude and duration of immunity, and that a cytokine-antigen fusion can push protection even further, gives researchers and control programs a concrete new tool to pursue. For a neglected disease that has waited decades for a technological leap, the arrival of one may finally be at hand.

Subject of Research: Development of EG95-based mRNA-lipid nanoparticle vaccines inducing long-term protective immunity against cystic echinococcosis

Article Title: Novel EG95-based mRNA vaccines induce long-term protective immunity against echinococcosis

Article References: Novel EG95-based mRNA vaccines induce long-term protective immunity against echinococcosis. (n.d.). https://doi.org/10.1371/journal.ppat.1014659

Image Credits: AI Generated

DOI: 10.1371/journal.ppat.1014659

Keywords: echinococcosis, Echinococcus granulosus, EG95, mRNA vaccine, lipid nanoparticles, zoonotic disease, veterinary vaccinology, humoral immunity, IL-4, parasitology, vaccine development, one health

The study enrolled 23 patients with muscle-invasive bladder cancer, stages T2 to T3b, who were undergoing radical radiotherapy delivered over four weeks alongside weekly gemcitabine chemotherapy. Blood samples were collected before the first radiation fraction and then every week until treatment ended. The researchers also retrieved each patient’s diagnostic biopsy and measured the activity of a validated 24-gene hypoxia signature, generating a hypoxia score for every tumour. Patients were then split into high and low hypoxia groups based on the median score. This design allowed the team to ask a deceptively simple question: do the proteins circulating in the blood of patients with oxygen-starved tumours look different from those in patients with well-oxygenated tumours, and do they change as treatment progresses?

Answering that question required overcoming a long-standing technical obstacle. Plasma is dominated by a small number of extremely abundant proteins, such as albumin and immunoglobulins, which mask the low-abundance molecules that often carry the most informative biological signals. Previous attempts to find circulating hypoxia markers relied on targeted antibody tests of single proteins, and several promising candidates, including osteopontin in head and neck cancer, ultimately failed prospective validation. The Manchester team took a different approach, using engineered liposomal nanoparticles roughly 105 nanometres in diameter as molecular fishing hooks. When incubated with plasma, these particles attract a shell of bound proteins, known as a protein corona, which preferentially captures lower-abundance molecules. The corona proteins were then purified, digested and analysed by high-resolution liquid chromatography tandem mass spectrometry.

The results were striking. Across all time points, the analysis identified 816 plasma proteins, of which 115 showed significant differences between patients with high and low tumour hypoxia scores, defined as a fold change greater than 1.5 and a p-value below 0.05. The number of differentially abundant proteins fluctuated across the treatment timeline: 24 before radiotherapy, 46 after one week, 40 after two weeks, 14 after three weeks and 37 at the end of treatment. Remarkably, roughly 45 percent of the differentially abundant proteins were immunoglobulins or complement cascade proteins, pointing to a previously underappreciated connection between tumour hypoxia and the humoral immune system, the antibody-producing arm of immunity.

From the full set of hypoxia-associated proteins, seven candidates stood out because they correlated significantly with tumour hypoxia scores at two or more time points and maintained a consistent direction of correlation throughout treatment. Five of them, IGKV3, IGLV2-18, VL_4 and VL_7 alongside the extracellular matrix protein FN1, were consistently elevated in patients with hypoxic tumours, while IGLV2-14 and CAMP were consistently reduced. Principal component analysis and K-means clustering showed that this seven-protein signature cleanly separated high-hypoxia from low-hypoxia patients, and, crucially, that the separation held steady at every time point during radiotherapy. That temporal stability is exactly what a clinically useful monitoring biomarker requires, since a signal that drifts unpredictably during treatment cannot guide real-time decisions.

Because only two of the seven proteins, FN1 and CAMP, had matching RNA expression data in public cohorts, the team distilled the signature into a two-gene version and validated it retrospectively in three independent bladder cancer cohorts. In the TCGA-BLCA cohort of 404 patients treated with cystectomy, high hypoxia scores predicted poorer ten-year overall survival with a hazard ratio of 1.54. In the BC2001 radiotherapy cohort of 313 patients, the hazard ratio was 1.42. A meta-analysis combining TCGA-BLCA, BC2001 and the BCON trial confirmed the association with poor prognosis across 150 patients, with a hazard ratio of 1.48, independently of age, sex, stage and treatment received. The signature also remained prognostic in patients treated with and without concurrent chemotherapy, suggesting its signal is not an artefact of a particular drug regimen.

The most clinically provocative finding came from the BCON phase III trial, which tested whether breathing carbogen, a mixture of oxygen and carbon dioxide, together with nicotinamide, a drug that improves blood flow, could sensitise hypoxic tumours to radiation. That trial previously showed a 17 percent improvement in five-year overall survival with hypoxia modification. When the new two-gene signature was applied to BCON samples, patients with high hypoxia scores had poorer survival in the radiotherapy-only arm but lost that disadvantage when treated with carbogen and nicotinamide, with a hazard ratio of 0.60 favouring hypoxia modification. In other words, the blood-based signature did not merely forecast prognosis; it predicted who would actually benefit from targeting hypoxia, mirroring the performance of the original 24-gene tumour biopsy signature but requiring only a blood draw.

Beyond the biomarker itself, the study revealed a dynamic biological story. Weighted correlation analysis grouped the 115 hypoxia-associated proteins into five co-expression clusters, each peaking at a successive point in the treatment timeline: before radiotherapy, and at weeks one through four. Every cluster was enriched for B cell response and immunoglobulin production pathways, while the pre-treatment cluster was uniquely enriched for extracellular matrix remodelling, and later clusters for coagulation, fibrin formation and metabolic processes. Comparing expression patterns with fold-change dynamics suggested that radiotherapy primarily drove the timing of cluster activation, whereas tumour hypoxia shaped the baseline abundance and magnitude of the response. The researchers propose that tumour re-oxygenation during radiotherapy, which generates reactive oxygen species and activates HIF-1 signalling, may explain the declining protein levels seen in later weeks of treatment.

The immunological implications extend well beyond bladder cancer. Prior laboratory work has shown that hypoxia-inducible factors directly regulate B cell maturation and immunoglobulin class switching, and mouse studies have demonstrated that germinal centre hypoxia can impair humoral anti-tumour responses. This study provides the first clinical, plasma-level evidence that such immune modulation occurs in patients, with hypoxic tumours showing a shifted immunoglobulin profile that evolves over the course of radiotherapy. The authors caution that the discovery cohort was small, included only two female patients, and lacked direct protein-level outcome validation, so prospective validation at the protein level is the essential next step. Even so, the work establishes nanoparticle-enabled proteomics as a powerful discovery platform for circulating cancer biomarkers and suggests a future in which a routine blood test could tell oncologists, week by week, whether a patient’s tumour is suffocating, whether radiation is working, and whether hypoxia-targeting drugs should be added to the plan.

Subject of Research: A plasma protein signature for detecting tumour hypoxia and predicting benefit from hypoxia-modifying radiotherapy in bladder cancer

Article Title: A plasma derived hypoxia signature predicts benefit from hypoxia-modifying radiotherapy and reveals dynamic humoral immune modulation in bladder cancer

Article References: Guerrero Quiles, C., Abumanhal-Masarweh, H., G. Abalos, J., Lodhi, T., Sanchez-Martinez, D., Reeves, K., James, N. D., Hall, E., Huddart, R. A., Porta, N., Hoskin, P., Biolatti, L. V., Hadjidemetriou, M., West, C. M., & Choudhury, A. (2026). A plasma derived hypoxia signature predicts benefit from hypoxia-modifying radiotherapy and reveals dynamic humoral immune modulation in bladder cancer. British Journal of Cancer. https://doi.org/10.1038/s41416-026-03603-x

Image Credits: AI Generated

DOI: 10.1038/s41416-026-03603-x

Keywords: bladder cancer, tumour hypoxia, radiotherapy, biomarker, proteomics, nanoparticles, protein corona, mass spectrometry, humoral immunity, BCON trial, carbogen and nicotinamide, liquid biopsy

The research team, led by Xuetong Zhu and Jiancheng Xu of the First Hospital of Jilin University in Changchun, China, together with colleagues from several Jilin institutions, assembled an unusually large immunological dataset. The analysis included 112 peripheral blood mononuclear cell samples, which allowed the investigators to probe T-cell responses, and 3,202 serum samples, which provided the statistical power needed to characterize antibody profiles across health and disease states. Using enzyme-linked immunosorbent assay to quantify antibody titers and enzyme-linked immunospot assay to measure cellular reactivity, the researchers built a two-pronged picture of what remains of vaccinia-induced immunity years after the last dose was administered.

The cellular arm of the study delivered a sobering message. Among individuals with historical smallpox vaccination, T-cell responses were limited, and — perhaps most strikingly — no significant differences were observed between healthy participants and those living with disease. In other words, the cellular memory that once formed a critical line of defense against variola virus and its relatives has thinned to a low, relatively flat baseline across the population studied. This matters because cell-mediated immunity is generally considered the more durable component of protection against orthopoxviruses, and its scarcity in previously vaccinated adults suggests that historical vaccination status alone cannot be assumed to confer meaningful cellular protection today.

The humoral picture was more nuanced and more clinically revealing. Vaccinated individuals with comorbidities had significantly lower immunoglobulin G titers against the vaccinia virus Tianan strain than their healthy counterparts, a difference that reached strong statistical significance with P values below 0.001. When the researchers broke the disease groups down into chronic disease subgroups, the variations persisted, indicating that the erosion of antibody memory is not a uniform process but one shaped by the specific burden of illness a person carries. Antibody titers are the standard surrogate for neutralizing capacity against orthopoxviruses, so lower titers in comorbid groups translate directly into a plausible reduction in protective buffering.

Regression analyses sharpened the risk stratification. Chronic disease was associated with lower odds of high antibody positivity, with an odds ratio of 0.67 and a 95 percent confidence interval of 0.44 to 0.98. Cancer carried an even stronger signal, with an odds ratio of 0.58 and a confidence interval of 0.37 to 0.90. These figures suggest that people with cancer who were vaccinated decades ago are roughly 40 percent less likely to maintain high-level antibody positivity than comparable healthy individuals. At the same time, the proportion of individuals with negative neutralizing antibody responses decreased with age — consistent with more of the oldest cohort having been vaccinated — but remained higher among disease groups than among healthy participants at every comparison point.

Beyond clinical diagnoses, the study uncovered associations between routine laboratory markers and antibody levels, offering a biochemical window into why some vaccinated individuals retain stronger humoral memory than others. High-density lipoprotein cholesterol, often called good cholesterol, showed a positive association with antibody levels, as did aspartate aminotransferase, an enzyme commonly monitored as a marker of liver and cellular turnover. Cholinesterase, by contrast, displayed an inverse association with antibody titers. While such correlations do not establish causation, they hint that metabolic and hepatic status may modulate the persistence of vaccine-induced humoral immunity, and they raise the possibility that routinely collected blood chemistry could help clinicians estimate residual orthopoxvirus protection without specialized immunological testing.

The second half of the study moved from measurement to simulation. The team constructed an exploratory susceptible-infected-recovered-dead model — a classic epidemiological framework that tracks individuals through states of susceptibility, infection, recovery, and death — parameterized with published epidemiological values rather than observed outbreak data. Within this framework, they simulated hypothetical transmission scenarios among immunocompromised populations to explore how reduced immune competence might alter the shape of an orthopoxvirus outbreak. The authors are careful to frame this modeling as exploratory and hypothetical, but the exercise provides a structured way to think about vulnerability that cannot ethically or practically be studied in real outbreaks.

The simulated scenarios produced an age-stratified pattern that public health planners will recognize as a double burden. In the model, immunocompromised individuals aged 15 to 19 years showed higher simulated infection proportions, suggesting that younger immunocompromised people — many of whom were never vaccinated and may have weakened immune systems due to disease or treatment — could contribute disproportionately to transmission in a hypothetical outbreak. At the other end of the age spectrum, individuals aged 70 and above showed higher simulated mortality proportions, reflecting the compounding of advanced age, waning or absent immunity, and reduced physiological reserve. Together, the two ends of the simulated curve sketch a scenario in which an orthopoxvirus introduction could simultaneously stress pediatric and adolescent transmission control and geriatric intensive care capacity.

The authors conclude that individuals with historical smallpox vaccination do show detectable residual immune responses, but that these responses vary meaningfully across comorbidity groups and correlate with measurable laboratory markers. They further suggest that immunocompromised individuals may warrant further evaluation for potential orthopoxvirus susceptibility — a recommendation that carries practical weight given that mpox clade outbreaks continue to evolve and that smallpox vaccines, including modern non-replicating formulations, are being redeployed in some settings. The study does not claim that previously vaccinated people are unprotected, nor does it establish that the modeled outbreak dynamics would occur in reality; its value lies in quantifying the heterogeneity of residual immunity and in providing a transparent, parameterized starting point for preparedness planning.

What emerges from the combined evidence is a portrait of a partially protected world. The generation vaccinated before routine smallpox immunization ended carries measurable but uneven antibody memory, eroded most in those with chronic disease and cancer, and supported by cellular responses too limited to distinguish the sick from the healthy. Meanwhile, younger immunocompromised people who never received the vaccine represent a structurally susceptible population in whom simulated outbreaks spread more readily. As the authors note, these findings may inform future orthopoxvirus preparedness and prevention strategies — from targeted serological screening of comorbid vaccinees to prioritized vaccination of immunocompromised cohorts — and they underscore a broader lesson of post-eradication immunology: population immunity is not a switch that stays on, but a gradient that shifts with age, health, and time.

Subject of Research: Residual smallpox vaccine immunity and orthopoxvirus outbreak modeling in immunocompromised populations

Article Title: Residual immune responses after historical smallpox vaccination and exploratory outbreak modeling in immunocompromised populations

Article References: Zhu, X., Wang, J., Wang, X., Tu, Z., Zhou, Q., Zhu, Y., & Xu, J. (2026). Residual immune responses after historical smallpox vaccination and exploratory outbreak modeling in immunocompromised populations. Journal of Translational Medicine. https://doi.org/10.1186/s12967-026-08907-3

Image Credits: AI Generated

DOI: 10.1186/s12967-026-08907-3

Keywords: smallpox vaccination, orthopoxvirus, mpox, neutralizing antibodies, immunocompromised, vaccinia virus, humoral immunity, cellular immunity, SIRD model, antibody titers, chronic disease, outbreak modeling

The rationale for targeting mucins rests on their central role in tick biology. Mucins are heavily glycosylated proteins that, in ticks, contribute to the formation of the cement cone that anchors the mouthparts into the host skin during feeding, help modulate the host immune response at the bite site, and participate in assembling the peritrophic membrane that lines the tick gut and protects it from ingested blood and microbes. Because these functions are essential to feeding and survival, proteins involved in them are attractive vulnerabilities: antibodies circulating in the host’s blood would be ingested by the tick and could interfere with these processes from within the parasite.

Before committing to laboratory production, the team characterized Mucin-6 using bioinformatic tools. The predictions indicated a hydrophilic but intrinsically unstable protein with a molecular mass of 24.9 kilodaltons after removal of its signal peptide, the short N-terminal sequence that normally directs secretion. Importantly for vaccine design, the sequence was predicted to be rich in linear B-cell epitopes, the short stretches of amino acids that antibodies can recognize on a denatured or soluble protein. Abundant epitopes increase the likelihood that vaccination will elicit a robust and specific humoral response, which is the arm of immunity most relevant for an antigen that will be encountered by the tick through a blood meal.

To confirm that the gene is biologically relevant throughout the tick life cycle, the researchers used quantitative PCR to measure Mucin-6 expression across developmental stages and feeding states. The gene was transcribed at every stage examined, from larva to adult, with significantly higher expression in eggs. This broad and consistent expression profile matters for vaccine utility: an antigen expressed only in a narrow stage or feeding condition would leave windows in which the parasite is unprotected, whereas a constitutively expressed protein offers a target throughout the tick’s interaction with the vaccinated host.

With the sequence validated, the team moved to recombinant production. The Mucin-6 coding sequence was cloned into the pET28a expression vector and transformed into BL21(DE3) Escherichia coli, a standard laboratory strain engineered for high-level protein expression under T7 promoter control. On induction, the recombinant protein accumulated in inclusion bodies, the dense aggregates of misfolded protein that bacteria often form when expressing foreign or disulfide-rich proteins. The researchers recovered the protein from these bodies, renatured it to restore a soluble conformation, and purified it using nickel-nitrilotriacetic acid affinity chromatography, which exploits the histidine tag encoded by the pET28a vector. On SDS-PAGE, the purified recombinant Mucin-6 migrated at approximately 41 kilodaltons, larger than the predicted 24.9 kilodaltons of the mature protein, a discrepancy consistent with the tag and the anomalous electrophoretic behavior typical of mucin-like, compositionally biased proteins.

The immunization trial used six New Zealand White rabbits randomly assigned to a vaccinated group of three and a phosphate-buffered saline control group of three. Each vaccinated rabbit received 500 micrograms of recombinant Mucin-6 formulated with Freund’s adjuvant in three subcutaneous injections spaced 14 days apart. Enzyme-linked immunosorbent assays tracked the antibody response, revealing titers that reached 1:512,000 by day 35, an exceptionally high level indicating strong recognition of the recombinant antigen. Fourteen days after the final booster, the researchers challenged each rabbit with 30 adult ticks, 15 males and 15 females, and measured the parameters that define tick vaccine efficacy: engorgement weight, egg mass, blood-feeding duration and egg-hatching rate.

The results showed a consistent, statistically significant burden on the parasites. Ticks that fed on immunized rabbits had engorged body weights reduced by 13.6 percent and egg masses reduced by 14.7 percent compared with ticks fed on control rabbits, both differences significant at P less than 0.05. Blood-feeding duration was prolonged by 8.3 percent, suggesting that antibodies disrupted the efficiency of feeding, forcing ticks to remain attached longer to obtain a full blood meal. Combining the effects on tick weight and fecundity, the authors calculated an overall vaccine efficacy of 26.3 percent. While modest compared with the best commercial anti-tick formulations, this figure represents a meaningful proof of concept for a single antigen tested in its first host species.

A critical question for any recombinant antigen is whether antibodies raised against the laboratory-produced protein also recognize the native version in the parasite. The team addressed this by western blot, incubating tick lysates with serum from the immunized rabbits. The anti-rMucin-6 serum bound native Mucin-6 in tick extracts, confirming that the recombinant protein preserved epitopes present in the authentic tick protein and that the antibodies generated in the vaccinated animals could, in principle, engage their target during a natural blood meal. This cross-recognition underpins the observed phenotypic effects and strengthens the case that Mucin-6, rather than an artifact of immunization, is the operative antigen.

The study sits within a broader effort to develop anti-tick vaccines that reduce both parasite loads and pathogen transmission without the drawbacks of chemical acaricides. The only commercially available tick vaccine, based on the gut antigen Bm86 against Rhipicephalus microplus, demonstrated decades ago that vaccinating the host can starve and sterilize ticks from within, but its efficacy varies across tick species and regions, driving the search for new antigens. Secreted proteins such as mucins, which are exposed to host antibodies in the ingested blood and are functionally indispensable, form a promising class of candidates. The Hainan team’s work adds Mucin-6 to this pipeline and demonstrates a complete workflow, from epitope prediction and expression profiling through prokaryotic production and a controlled animal challenge.

Limitations remain before Mucin-6 could approach practical deployment. The trial involved a small number of animals, a single antigen and a single host species, and Freund’s adjuvant is unsuitable for veterinary or human use, so future work would need to test the antigen with licensed adjuvants, in larger cohorts, and ideally in combination with other antigens to push efficacy higher. The authors, led by corresponding author Qingfeng Guan with co-first authors Jie Chen and Yongchuan Zhu, conclude that Mucin-6 merits further evaluation as a candidate vaccine antigen against R. linnaei. Given that tick-borne diseases continue to expand their geographic range with changing climates and livestock movements, even incremental gains from antigen discovery of this kind carry substantial implications for animal health and the economics of tick control.

Subject of Research: Evaluation of the tick protein Mucin-6 from Rhipicephalus linnaei as a recombinant anti-tick vaccine antigen

Article Title: Prokaryotic expression and vaccine potential of Mucin-6 from Rhipicephalus linnaei

Article References: Chen, J., Zhu, Y., Zhao, J., Wang, J., Han, Q., & Guan, Q. (2026). Prokaryotic expression and vaccine potential of Mucin-6 from Rhipicephalus linnaei. Parasites & Vectors. https://doi.org/10.1186/s13071-026-07675-9

Image Credits: AI Generated

DOI: 10.1186/s13071-026-07675-9

Keywords: Rhipicephalus linnaei, Mucin-6, anti-tick vaccine, recombinant protein, prokaryotic expression, vaccine efficacy, tick control, humoral immunity, B-cell epitopes, Parasites & Vectors, livestock health, vector biology

The study drew on 289 children enrolled in the PROGRESS cohort in Mexico, a long-running birth cohort designed to examine how environmental exposures shape child health. Rather than relying on blood or urine samples, which capture only recent exposure, the researchers turned to deciduous teeth, the baby teeth that children naturally shed. Teeth grow in layers much like tree rings, and the dentine that forms during specific developmental periods locks in a chemical record of what circulated in the child’s bloodstream at the time. By segmenting dentine along growth lines, the team was able to retrospectively quantify arsenic exposure for every week from sixteen weeks before birth through fourteen weeks after birth, an unprecedented temporal resolution for an immunotoxicology study.

When the children returned for a follow-up visit around age four to five, the investigators measured serum levels of immunoglobulin G antibodies directed against six vaccine antigens: measles, mumps, and rubella from the MMR vaccine, and diphtheria, tetanus, and pertussis from the DTP series. These antibodies are the immune system’s memory of vaccination, the molecular shield that prevents re-infection, and their concentrations in blood are a standard benchmark of how well a vaccine has taken hold. The measurements were performed using a multiplexed Luminex bead-based immunoassay, a technique that allows all six antibody targets to be quantified simultaneously from a small serum sample.

The statistical challenge was considerable. Because arsenic exposure was estimated for thirty consecutive weeks, the researchers needed a method that could detect when in that timeline exposure mattered, not just whether it mattered overall. They employed Distributed Lag Non-linear Models, or DLNMs, a framework originally developed in environmental epidemiology for studying delayed and time-varying effects of air pollution and temperature. The models related log2-transformed dentine arsenic concentrations to log2-transformed antibody levels across every week of the perinatal period, while adjusting for the child’s age, maternal education, parity, and child sex. The log2 transformation means the reported effects can be read as the change in antibody level associated with a doubling of arsenic exposure during a given week.

The results converged on a single, well-defined period. A doubling of arsenic exposure in the window spanning one week before birth to six weeks after birth was associated with significantly lower anti-measles antibody levels, with an estimated effect of minus 5.62 on the log2 scale and a 95 percent confidence interval running from minus 8.39 to minus 0.83. The same perinatal window showed a significant association for anti-rubella antibodies, with an effect estimate of minus 3.85 and a confidence interval from minus 6.99 to minus 0.63. In practical terms, children with higher arsenic exposure in the weeks surrounding delivery carried measurably weaker antibody defenses against measles and rubella years later, even though their vaccinations occurred long after the exposure itself.

Just as telling was what the analysis did not find. Arsenic exposure during the perinatal window showed no significant association with antibody levels against mumps, diphtheria, tetanus, or pertussis. Nor did earlier or later periods of prenatal and early postnatal exposure produce significant signals for any antigen. This selectivity is biologically intriguing. It suggests that the immune pathways supporting long-term antibody maintenance against measles and rubella may be more sensitive to arsenic’s interference than those supporting the other four antigens, or that different vaccine antigens rely on differently timed developmental programs of B-cell and plasma-cell maturation that vary in their vulnerability to toxic insult.

The timing of the susceptible window makes biological sense. The weeks surrounding birth are a period of profound immunological transition. The fetus must shift from the sterile, maternally protected environment of the womb to an microbe-rich world, and neonatal immune cells are actively learning to distinguish threat from tolerance. Maternal antibodies transferred across the placenta are waning while the infant’s own antibody production is just beginning. Arsenic is known to disrupt immune signaling, generate oxidative stress, and interfere with methylation processes that regulate gene expression, and a toxic exposure during this delicate choreography could plausibly leave a lasting imprint on how well vaccine memory is established and maintained.

The researchers also probed whether the effects differed between boys and girls, or between children who were breastfed at one month postpartum and those who were not, since both factors can shape immune development and arsenic dynamics. They found no heterogeneity by either sex or breastfeeding status, indicating that the association between perinatal arsenic and reduced measles and rubella antibodies appears to operate similarly across these subgroups. That consistency strengthens the case that the finding reflects a general biological vulnerability rather than an effect confined to a particular subset of children.

The methodological innovation deserves particular attention. Traditional exposure assessment in environmental health has long been hampered by the difficulty of reconstructing what a person was exposed to years or decades earlier. Baby teeth offer a solution that is both retrospective and precise, and their use here demonstrates how naturally shed biomaterials can transform the study of developmental toxicology. Combined with the DLNM framework, which treats exposure timing as a variable to be mapped rather than averaged, the approach allowed the team to draw a temporal map of vulnerability with weekly resolution, something conventional single-biomarker studies simply cannot achieve.

The public health implications are significant. Measles remains one of the most contagious human pathogens, and even modest reductions in population-level antibody levels can erode herd immunity and fuel outbreaks, a concern made vivid by recent resurgences of measles in countries where the disease was once controlled. Arsenic contamination of groundwater affects an estimated hundreds of millions of people worldwide, and in regions such as Mexico, where the PROGRESS cohort is based, exposure often begins before birth. If the findings are confirmed in other cohorts, they would add vaccine-preventable disease susceptibility to the long list of harms attributable to early-life arsenic exposure, and they would sharpen the argument for reducing arsenic exposure among pregnant women and newborns, whether through water filtration, dietary interventions, or regulatory limits on contaminated sources. The study, funded by the National Institutes of Health and led by researchers at the Icahn School of Medicine at Mount Sinai together with collaborators at Mexico’s National Institute of Public Health and other institutions, was published open access, with the authors reporting no competing interests.

Subject of Research: Perinatal arsenic exposure and vaccine-specific antibody levels in children

Article Title: Susceptible perinatal windows to arsenic exposure and serum antibody levels in children

Article References: Scotti, A., India-Aldana, S., Martinez, M., Arora, M., McRae, N., Lamadrid-Figueroa, H., Quataert, S. A., Estrada-Gutierrez, G., Torres-Olascoaga, L., Téllez-Rojo, M. M., Wright, R. O., Jusko, T. A., & Colicino, E. (2026). Susceptible perinatal windows to arsenic exposure and serum antibody levels in children. Environmental Health. https://doi.org/10.1186/s12940-026-01331-6

Image Credits: AI Generated

DOI: 10.1186/s12940-026-01331-6

Keywords: arsenic exposure, perinatal window, vaccine antibodies, measles, rubella, immunotoxicology, baby teeth, dentine, PROGRESS cohort, DLNM, humoral immunity, environmental health