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Aim Methods Results Conclusion Pregnant women are at increased risk for severe illness associated with coronavirus disease 2019 (COVID‐19) compared to nonpregnant women. The aim of this multicenter prospective study was to assess the current COVID‐19 vaccination status of pregnant women in the southern Osaka district and to compare their antibody titers with those of nonpregnant women.Serum antibody titers of anti‐NCP antibodies (antibodies against the SARS‐CoV‐2 nucleocapsid) and anti‐RBD antibodies (the receptor binding domain of the S1 subunit of the spike protein) were evaluated in 753 pregnant women at 34–35 weeks of gestation from October 2021 to March 2022. Anti‐RBD antibody titre was also investigated in 1003 health care workers at Kindai University hospital 3 and 6 months after a second dose of the vaccine from March 2021 to April 2021. 519 (68.9%) pregnant women were vaccinated during pregnancy, of whom 497 (95.8%) received two doses.The COVID‐19 infection rate calculated from the number of pregnant women with a positive anti‐NCP antibody titre or with confirmed diagnosis was 5.1% (12/234) in the unvaccinated and 3.5% (18/519) in the vaccinated. The estimated half‐life calculated from anti‐RBD antibody titers and the number of days between vaccination and antibody testing was 39.9 days. The antibody titre and half‐life in pregnant women were significantly lower and shorter than in nonpregnant women aged 20–39 years (109.4 days).Our study showed that pregnant women may have lower vaccine‐acquired COVID‐19 immunity than nonpregnant women. [ABSTRACT FROM AUTHOR]

Background and Aims Methods Results Interpretation Hyaluronidase‐facilitated subcutaneous immunoglobulin (fSCIG) consists of subcutaneous human immunoglobulin G (IgG) 10% with recombinant human hyaluronidase (rHuPH20) and can be administered at the same dose and interval as intravenous IgG (IVIG). fSCIG recently received US approval as maintenance therapy for adults with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and European approval for adults and children with CIDP after stabilization with IVIG.ADVANCE‐CIDP 3 (NCT02955355) was an open‐label long‐term extension of the Phase 3 double‐blind randomized placebo‐controlled ADVANCE‐CIDP 1 study (NCT02549170) that examined fSCIG safety and efficacy as maintenance CIDP therapy. Primary outcomes were safety, tolerability, and immunogenicity. Efficacy was an exploratory outcome.The study provided 220 patient‐years of follow‐up data from 85 patients. Median (range) exposure was 33 (0–77) months. Patients received fSCIG every 4 weeks (88.2%) or every 3 weeks (11.8%). Median (range) 4‐weekly IgG dose equivalent was 64.0 (28.0–200.0) g. Mean (standard deviation) infusion duration was 135.5 (62.8) minutes. Most adverse events (AEs) were mild or moderate and self‐limiting. Of the 1406 AEs, only 48 were severe and 30 were serious. fSCIG‐related AEs (n = 798) included infusion site reactions such as pain, redness, and pruritus. Three infusions (0.1%) were reduced in rate, interrupted, or stopped due to intolerability. Relapse occurred in 10 of 77 patients (13.0%); annual relapse rate was 4.5%. An anti‐rHuPH20 antibody titer ≥1:160 was detected in 14 of 84 patients (16.7%); patients who tested positive (≥1:160) had similar relapse rates versus those who tested negative (16.7% vs. 12.3%, respectively).ADVANCE‐CIDP 3 demonstrated favorable fSCIG long‐term safety and tolerability consistent with its established safety profile, and a low relapse rate, supporting use as maintenance CIDP treatment. [ABSTRACT FROM AUTHOR]

To evaluate experience in a tertiary rheumatology service with melanoma differentiation‐association‐protein‐5 (MDA5) disease and testing, patients with positive autoantibody results were reviewed for the presence of clinical disease. Anti‐MDA5 positivity was detected in 2% of myositis‐specific antibody tests. Of these, 29% did not have features consistent with anti‐MDA5 disease. However, when present, MDA5 disease is severe with a high mortality. [ABSTRACT FROM AUTHOR]

Background: Zaire Ebolavirus disease (EVD) outbreaks can be controlled using rVSV-ZEBOV vaccination and other public health measures. People in high-risk areas may have pre-existing antibodies from asymptomatic Ebolavirus exposure that might affect response to rVSV-ZEBOV. Therefore, we assessed the impact pre-existing immunity had on post-vaccination IgG titre, virus neutralisation, and reactogenicity following vaccination. Methods: In this prospective cohort study, 2115 consenting close contacts ("proches") of EVD survivors were recruited. Proches were vaccinated with rVSV-ZEBOV and followed up for 28 days for safety and immunogenicity. Anti-GP IgG titre at baseline and day 28 was assessed by ELISA. Samples from a representative subset were evaluated using live virus neutralisation. Results: Ten percent were seropositive at baseline. At day 28, IgG in baseline seronegative (GMT 0.106 IU/ml, 95% CI: 0.100 to 0.113) and seropositive (GMT 0.237 IU/ml, 0.210 to 0.267) participants significantly increased from baseline (both p < 0.0001). There was strong correlation between antibody titres and virus neutralisation in day 28 samples (Spearman's rho 0.75). Vaccinees with baseline IgG antibodies against Zaire Ebolavirus had similar safety profiles to those without detectable antibodies (63.6% vs 66.1% adults experienced any adverse event; 49.1% vs 60.9% in children), with almost all adverse events graded as mild. No serious adverse events were attributed to vaccination. No EVD survivors tested positive for Ebolavirus by RT-PCR. Conclusions: These data add further evidence of rVSV-ZEBOV safety and immunogenicity, including in people with pre-existing antibodies from suspected natural ZEBOV infection whose state does not blunt rVSV-ZEBOV immune response. Pre-vaccination serological screening is not required. [ABSTRACT FROM AUTHOR]

Background Study Design and Methods Results Discussion Transfusion‐transmitted malaria (TTM) is rare in non‐endemic areas (non‐EAs) but can potentially be fatal. This review analyzes the laboratory results of donors causing TTM in non‐EAs, to assess the detectability of their Plasmodium infection by molecular or antibody tests.TTM cases in the United States, Canada, and Europe since 2010 were identified through a literature review. Authors and laboratories were contacted for missing details about sample types and laboratory methods. Results of Plasmodium polymerase chain reaction (PCR) and antibody tests were summarized.Twelve cases of TTM and one bone marrow transplant transmission were identified. Of the 13 source donors, 12 were tested by PCR, 10 were positive on at least one sample; the 2 negative donors were tested only on retained segments of blood refrigerated for several weeks. All donors were PCR positive on a fresh sample except one who was positive on a retained but not a fresh sample. These PCRs targeted Plasmodium DNA with sensitivities in the range of 1000–10,000 parasites/mL. Antibody EIA was positive in only three of seven donors tested.This review found that antibody EIAs failed to detect four of the seven TTM donors tested. DNA‐based PCRs were able to detect Plasmodium infection in all donors tested except for two tested only on samples likely to have deteriorated from prolonged storage. Recently developed ribosomal RNA‐based molecular donor screening assays are approximately 1000 fold more sensitive than these DNA‐based PCRs, holding promise as a potential method to further reduce TTM. [ABSTRACT FROM AUTHOR]

We conducted research studies on avian reovirus (ARV) infectivity in egg-laying hens, focusing on three variants (δC genotypes 2, 3, and 5) detected in layer chickens in Pennsylvania to date. Day-old chicks (Hy-Line North America, LLC, PA), raised at the Poultry Education and Research Center of Penn State University Park campus, showed healthy growth and normal egg production after 20 weeks of age. ARV variants were propagated in LMH cell cultures, with concentrations measured at TCID50/mL. Each group of 10 hens received a 1.0 mL dose containing 103 to 104 TCID50/mL of one ARV variant through oral, nasal, and ocular routes. Infected hens showed normal egg production, with minimal symptoms of watery droppings in the first-week post-inoculation (pi). Cloacal and oral pharyngeal swabs were collected daily in the first week pi and every other day in the second-week pi to monitor virus shedding. Virus shedding began 24 hours pi through feces, peaked at 2 to 4 days pi, decreased by 5 to 7 days pi, and ceased after 12 to 14 days pi. A few birds’ oral pharyngeal swabs were weakly positive for 1 to 3 days pi, then all turned negative. Infected hens developed high serum and egg yolk antibody titers at 2 to 3 weeks pi, showing 100% protection against subsequent infections with the same variant strain, demonstrating a 100% protection rate. [ABSTRACT FROM AUTHOR]

Introduction: ABO-incompatible (ABOi) kidney transplantation (KT) has become an important option to overcome organ shortage. Plasmapheresis/rituximab-based desensitization therapy has successfully reduced anti-ABO antibody levels and suppressed antibody-mediated rejection (AMR) in ABOi KT. However, high titers of anti-ABO antibodies in some patients are refractory to standard desensitization, leading to loss of KT opportunities or AMR. Methods: Eculizumab treatment was used an adjunctive therapy to rescue high-titer ABOi KT patients refractory to plasmapheresis/rituximab-based desensitization. Molecular phenotypes of allograft biopsies and cellular phenotypes of peripheral blood mononuclear cells of eculizumab group were compared with those of control groups using the Banff Human Organ Transplant gene panel and flow-cytometric analysis, respectively. Results: The initial titers of anti-ABO antibodies in the two patients were 1:512 and >1:1024; the final pre-transplant titers after desensitization were 1:128 and 1:64. Both patients received eculizumab from KT day to two or four weeks post-KT and maintained stable renal function up to one-year post-transplantation without overt infection, despite early episodes of probable AMR or borderline T cell-mediated rejection. Molecular phenotype analysis revealed that gene expression patterns in the ABOi KT with eculizumab group overlapped with those in the ABOi KT with AMR group more than in the ABOi KT without AMR group, except for complement pathway-related gene expression. Anti-ABO antibody titers decreased to low levels 1–3 months post-transplant in the eculizumab group in parallel with decreasing anti-B-specific B cells. Conclusions: Short-term eculizumab therapy is promising for rescuing ABOi KT recipients with high anti-ABO antibody titers refractory to plasmapheresis-based desensitization therapy. [ABSTRACT FROM AUTHOR]

Voltage-gated potassium channel (VGKC) complex autoimmunity associated with nerve hyperexcitability is an uncommon clinical spectrum. It is mostly characterized by limbic encephalitis, continuous neuromyotonia, and dysautonomia. Pain, however, has rarely been reported as the first symptom. The present study describes a case of persistent neuropathic pain as the only symptom associated with a positive serum contactin-associated protein-like 2 (CASPR2) auto-antibody in a 41-year-old female patient. Her pain was completely relieved with steroids and intravenous immunoglobulin (IVIG) therapy. Nevertheless, the pain recurred 1 year later, consistent with an immunofluorescence titer of the CASPR2 antibody. Our case shows that neuropathic pain may occur as the first and only manifestation of a VGKC complex autoimmunity disorder. VGKC antibody titers might be an indication of pain severity. Steroids coupled with IVIG are effective, but relapse may still occur. [ABSTRACT FROM AUTHOR]

Background: Defining the protective thresholds against the severe-acute-respiratory-syndrome-related corona virus-2 pandemic is a crucial challenge. To reduce the risks of severe disease, hospitalization, and death, various COVID-19 vaccines have been rapidly developed. Aim of the work: This study aimed to assess the impact of three common COVID-19 vaccine types; two mRNA COVID-19 vaccines: (Pfizer/BioNTech's BNT162b2 and Moderna's mRNA-1273), one adenoviral vector vaccine: Oxford/AstraZeneca's ChAdOx1, and one inactivated vaccine (Sinovac Biotech/China's Sinovac) on the level of neutralizing antibodies, considering factors such as vaccine type, demographic characteristics, and hybrid immunity. We conducted a direct comparative analysis involving 300 healthcare workers, both with and without prior SARS-CoV-2 infection (B.1, C.36.3, and AY.32 (Delta) variants). Neutralizing antibodies levels were measured at baseline (before vaccination), before the second dose, and six months after the second dose. Results: The results showed a significant increase in neutralizing antibodies levels after complete vaccination with all vaccine types. Among healthcare workers, those vaccinated with mRNA vaccines (Moderna or Pfizer) exhibited the highest neutralizing antibodies titers, followed by AstraZeneca, and finally Sinovac with the lowest titer. On studying the effect of previous COVID-19 infection after vaccination, no significant difference in neutralizing antibodies levels was observed between healthcare workers vaccinated with mRNA or AstraZeneca vaccines, both with prior COVID-19 infection, following the first and six months after the second dose. Conclusion: These findings suggest that individuals with prior COVID-19 may only require a single dose of mRNA or AstraZeneca vaccines to achieve a similar level of immunization as those without prior COVID-19 who completed the vaccination program. Highlights: There is a significant increase in neutralizing antibodies levels after complete vaccination against COVID-19 Vaccination with mRNA vaccines exhibits the highest neutralizing antibodies titers. Vaccination with Sinovac exhibits the lowest neutralizing antibodies titers. [ABSTRACT FROM AUTHOR]

Objective: Cyclophosphamide (CTX) is an effective anticancer drug, but toxic effects against normal human tissues are its dose-limiting drawback. The aim of this research was to investigate the in vivo immunomodulatory activities of Allium ampeloprasum Subsp Iranicum against CTX-induced toxicity in mice. Materials and Methods: Extract of the whole plant of A. ampeloprasum Subsp Iranicum was obtained using the maceration technique, and its total phenolic and flavonoid contents were quantified through spectrophotometric analysis. Mice received daily oral administration (PO) of the extract (150 mg/kg) for a duration of 14 days, either as a standalone treatment or in conjunction with an intraperitoneal (IP) injection of 20 mg/kg CTX. The effects of the extract on body weight, spleen weight, white blood cell (WBC), serum antibody titer hemagglutination (HA), delayed-type hypersensitivity response (DTH), lymphocyte proliferation, cytokine production, and histopathological examinations were evaluated. Results: A. ampeloprasum Subsp Iranicum restored several parameters including spleen weight (p<0.001), WBC (p<0.001), lymphocytes (p<0.05), and monocytes (p<0.01), HA titer (p<0.05), and DTH response (p<0.01). A. ampeloprasum Subsp Iranicum notably stimulated lymphocyte proliferation to PHA (p<0.01) and LPS (p<0.05) and recovered interferon (IFN)-γ (p<0.001) and interleukin (IL)-4 (p<0.001) levels in the immunosuppressed mice. Also, CTX-induced histopathological changes were reversed by A. ampeloprasum Subsp Iranicum . Conclusion: Analyses revealed A. ampeloprasum Subsp Iranicum could regulate immunity and increase host immune responses. The observed strengthening effect can be attributed to the high amount of flavonoids and dipropyl trisulfide compounds present in A. ampeloprasum Subsp Iranicum. [ABSTRACT FROM AUTHOR]

N -terminal acetylation is being recognized as a factor affecting protein lifetime and proteostasis. It is a modification where an acetyl group is added to the N -terminus of proteins, and this occurs in 80 % of the human proteome. N -terminal acetylation is catalyzed by enzymes called N -terminal acetyltransferases (NATs). The various NATs acetylate different N -terminal amino acids, and methionine is a known target for some of the NATs. Currently, the acetylation status of most proteins can only be assessed with a limited number of methods, including mass spectrometry, which although powerful and robust, remains laborious and can only survey a fraction of the proteome. We here present testing of an antibody that was developed to specifically recognize Nt-acetylated methionine-starting proteins. We have used dot blots with synthetic acetylated and non-acetylated peptides in addition to protein analysis of lysates from NAT knockout cell lines to assess the specificity and application of this anti-Nt-acetylated methionine antibody (anti-NtAc-Met). Our results demonstrate that this antibody is indeed NtAc-specific and further show that it has selectivity for some subtypes of methionine-starting N -termini, specifically potential substrates of the NatC, NatE and NatF enzymes. We propose that this antibody may be a powerful tool to identify NAT substrates or to analyse changes in N -terminal acetylation for specific cellular proteins of interest. • The function and regulation of Nt-acetylation is unknown for most proteins. • We evaluated a pan Nt-acetylation antibody as a method to monitor Nt-acetylation. • We used peptide dot blot, WB of NAT KO cell lysates, and MS of mouse tissue. • Met-hydrophobic starting N -termini are most suitable for NtAc-dependent detection with this antibody. • The antibody may be used for various Met-starting proteins, to be validated with peptide. [ABSTRACT FROM AUTHOR]

Introduction: Feline calicivirus (FCV) commonly causes upper respiratory tract, oral and ocular infections in species of the family Felidae, with high prevalence amongst domestic cat (Felis catus) populations worldwide. Detection of FCV‐specific antibodies in serum provides evidence of previous infection with FCV and an indication of whether a cat may be protected against clinical FCV disease. This study describes the most extensive sampling for anti‐FCV antibodies in feral and stray cat populations in Australia, and examines variation in prevalence associated with cat age, sex and location. Methods: Blood samples were opportunistically collected from 669 feral, stray or Indigenous community cats from the Northern Territory, South Australia, Victoria, south‐east Tasmania and south‐west New South Wales. The sera were harvested and tested for antibodies capable of neutralising the FCV vaccine strain F9 by serum‐virus neutralisation assay. Results: Of the 669 cats tested, 69.7% had detectable FCV‐F9‐neutralising antibodies (titres ≥5). Maturity was significantly associated with higher seroprevalence and higher antibody titres, with adult cats being more than twice as likely to have detectable FCV‐neutralising antibodies than subadults. Male cats had a higher seroprevalence and slightly higher antibody titres than females. Cats living in closer proximity to humans had significantly higher seroprevalences and higher FCV‐neutralising antibody titres than feral cats from more remote regions of Australia. Conclusion: Australian feral and stray cats have a high risk of natural exposure to and infection with FCV, with the prevalence and levels of pre‐existing immunity to FCV being highest amongst adult cats living in highly modified urban, peri‐urban and agricultural environments. [ABSTRACT FROM AUTHOR]

The role of immunosuppressive therapy on SARS-CoV-2 infection risk and COVID-19 severity remains unclear in unvaccinated solid organ transplant recipients. We included 1957 organ transplant recipients between July 2020 and April 2021 to analyze whether baseline immunosuppressive therapy and other risk factors are associated with SARS-CoV-2 infection and severe COVID-19. In total, 247 (12.6%) had SARS-CoV-2 (defined as positive nasopharyngeal swab and/or positive antibody titer). Of these, 57 (23.1%) had severe COVID-19, defined as oxygen supplementation, intensive care unit admission or death. Multivariable analysis identified diabetes (hazard ratio (HR) 1.39 (95% confidence interval (CI) 1.05–1.83)), chronic lung disease (HR 1.71 (95% CI 1.13–2.60)) and contact with a COVID-19 positive individual (HR 3.61 (95% CI 2.61–4.99) as independent risk factors for SARS-CoV-2 infection. There was no association between immunosuppressive therapy and infection risk. Severe COVID-19 was multivariably associated with hypertension (OR 5.45 (95% CI 1.66–17.84)), chronic kidney disease (OR 3.55 (95% CI 1.75–7.19)), corticosteroid use (OR 2.93 (95% CI 1.03–2.55)) and having a COVID-19 positive housemate (OR 6.77 (95% CI 2.65–17.28)). In conclusion, baseline corticosteroid use, but no other immunosuppressive agent, is independently associated with severe COVID-19 in unvaccinated SOT recipients after correction for hypertension, chronic kidney disease, housemates affected by COVID-19 and transplant type. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Hepatitis E virus (HEV) is a major global health issue, with an estimated 20 million infections annually. Although polymerase chain reaction (PCR) is the diagnostic gold standard due to its precision, it is expensive and technically demanding. Antibody tests offer a more practical and cost‐effective alternative, although their accuracy can vary due to factors, such as test manufacturer, antigen composition, HEV genotype, and host immune status.A comprehensive search was conducted in PubMed, Cochrane, Scopus, and Web of Science databases. Studies included comparing the sensitivity and specificity of immunoglobulin M or immunoglobulin G antibody tests to PCR. Exclusion criteria were non‐PCR comparisons, sample sizes under 10, IgA or antigen tests, non‐human samples, or missing sensitivity and specificity data. Only English‐language full‐texts or abstracts were considered. Data analysis was performed using Meta‐DTA v2.1.1 and Stata 16.0.The meta‐analysis evaluated 8054 blood samples from 21 studies. Immunoglobulin M antibody tests demonstrated an overall sensitivity of 83% (95% CI 76–88) and specificity of 98% (95% CI 97–99). Immunoglobulin G tests showed a sensitivity of 74% (95% CI 62–82) and specificity of 89% (95% CI 84–93). Among manufacturers, Wantai was the most accurate for immunoglobulin M detection, whereas MP led for immunoglobulin G. Notably, test sensitivity improved when the test protein genotype aligned with the HEV genotype.This meta‐analysis confirmed that antibody assays have a good sensitivity and high specificity to detect HEV infection in situations where PCR is not feasible, highlighting their potential as a practical diagnostic tool. [ABSTRACT FROM AUTHOR]

• Prevalence of high titers for IgM anti-A was 12.2% and IgG anti-A was 2.5%, with lower prevalence for anti-B antibodies. • Among blood donors, 14.1% of those with O blood groups were classified as Dangerous O, while 3.52% and 10.5% of donors with A and B blood groups, respectively, exhibited high titers. • Significant associations were found between high titers and factors like female gender, vegetarian diet, age under 30 years, and O blood group. Hemolytic transfusion reactions (HTRs) pose significant risks in transfused patients, with anti-A and anti-B antibodies in donor plasma being potential contributing factors. Despite advancements in component preparation, HTRs remain a concern, particularly with apheresis-derived platelets. This study aimed to determine the prevalence of high anti-A and anti-B titers among A, B, and O blood group donors and to explore factors associated with high titers. A cross-sectional observational study was conducted over 18 months, enrolling 978 participants from a tertiary care teaching hospital in Western India. Anti-A and anti-B titers were determined using the Conventional Tube Technique (CTT). Statistical analysis assessed correlations between high titers and demographic factors. The majority of participants were young males (98.8%). Prevalence of high titers for IgM anti-A was 12.2% and IgG anti-A was 2.5%. For anti-B, IgM titers were 2.3% and IgG titers were 0.2%. The prevalence of dangerous O was found to be 14.1%, while 3.52% and 10.5% of A and B blood group donors were found to have high titers, respectively. Factors associated with high titers included female gender, vegetarian diet, age <30 years, and O blood group. The study sheds additional light and provides supplementary information regarding the prevalence and correlation of high anti-A and anti-B titers among O, A and B blood donors. Understanding these factors is crucial for optimizing transfusion safety protocols, including selective screening of platelet units and tailored transfusion strategies based on donor characteristics. [ABSTRACT FROM AUTHOR]

We studied SARS-CoV-2 binding and neutralizing antibody titers among previously infected persons in the United States over time. We assayed SARS-CoV-2 spike protein receptor-binding domain and neutralizing antibody titers for a convenience sample of residual clinical serum specimens that had evidence of prior SARS-CoV-2 infection gathered during January 2021-February 2022. We correlated titers and examined them by age group (<18, 18-49, 50-64, and >65 years) across 4 different SARS-CoV-2 variant epochs. Among selected specimens, 30,967 had binding antibody titers and 744 had neutralizing titers available. Titers in specimens from children and adults correlated. In addition, mean binding antibody titers increased over time for all age groups, and mean neutralization titers increased over time for persons 16-49 and >65 years of age. Incorporating binding and neutralization antibody titers into infectious disease surveillance could provide a clearer picture of overall immunity and help target vaccination campaigns. [ABSTRACT FROM AUTHOR]

Masticatory myositis (MM) is an inflammatory myopathy reported in dogs and is characterized by inflammation of the masticatory muscles (temporalis, masseter, and pterygoid muscles). Immunosuppressive therapy is the current recommended treatment for MM and may involve glucocorticoids, cyclosporine, azathioprine, mycophenolate mofetil, leflunomide, or a combination of these treatments that are slowly tapered to the lowest effective dose. However, side effects from multimodal medical therapy and complications associated with MM relapses have been reported. The purpose of this case series was to report oclacitinib as a treatment alternative to traditional medical management of MM. The intent of this alternative is to manage side effects from glucocorticoid use. Oclacitinib (1mg/kg per os q12h) was used solely for treatment of MM in three dogs. The dogs were followed up to >6 months after oclacitinib administration. An increase in oral range of motion, as determined by gape angle, was noted in all three dogs. However, a corresponding drop in antibody titers (2M fiber) did not occur. All dogs showed improvement in overall clinical management of MM, side effects from glucocorticoids, and clinical signs related to chronic prednisone use. Larger controlled trials with consistent measurements (interincisal distance, gape angle) and 2M fiber antibody titers are indicated to further assess validation of oclacitinib treatment of MM. The clinical outcome of all dogs was considered successful. [ABSTRACT FROM AUTHOR]

Neurolisteriosis, a common disease of small ruminants, is most often caused by Listeria monocytogenes. Here we describe 25 cases of caprine neurolisteriosis diagnosed in our laboratory over a 5-y period and compare our fluorescent antibody test (FAT) results with immunohistochemistry (IHC) and polymerase chain reaction (PCR) testing for diagnostic confirmation. Neurohistologic changes consistent with neurolisteriosis affected the pons in all cases, extending rostrally to the mesencephalon in 6 cases, caudally to the medulla oblongata in 6 cases, and/or dorsally to the cerebellum in 4 cases. Acute inflammatory changes were observed in 17 cases, and included neuroparenchymal microabscesses, neuronal necrosis and neuronophagia, axonal swelling, microgliosis and astrogliosis, and perivascular neutrophils with macrophages, lymphocytes, and plasma cells that occasionally extended to the leptomeninges. Subacute-to-chronic changes (8 cases) consisted of neuroparenchymal and perivascular clusters of macrophages with rare neutrophils, lymphocytes, and plasma cells admixed with glial nodules. Bacterial bacilli were observed within neutrophils or macrophages in H&E-stained tissue sections in 4 cases. Gram stain highlighted gram-positive bacilli in 13 cases. Neurolisteriosis was confirmed by FAT in 2 cases, by IHC in 19 cases, and by PCR in 20 cases. [ABSTRACT FROM AUTHOR]

African swine fever (ASF) is a high-consequence transboundary animal disease caused by African swine fever virus (ASFV). Given that vaccines are not widely available, ASFV detection, including by molecular and serologic assays, is paramount to efficacious control and mitigation of ASF. ASFV-specific antibodies can be detected as early as 7–10 d postinfection in infected animals and may persist for several months or longer. Accurate detection of ASFV-specific antibody is critical for the identification of chronically infected, subclinically infected, or recovered animals. ELISAs are commonly used for the rapid screening of large numbers of animals for ASFV antibodies. The World Organisation for Animal Health recommends that ELISA-positive results should be confirmed with a second serologic method, such as an indirect immunofluorescent assay, indirect immunoperoxidase test (IPT), or immunoblot test. Commercial kits are not available for those tests. We developed and validated an in-house IPT by using a currently circulating genotype II ASFV strain as antigen. The sensitivity and specificity of the in-house IPT are comparable to the reference IPT developed by an international ASFV reference laboratory and superior to a commercial blocking ELISA. [ABSTRACT FROM AUTHOR]

Background: In areas where C. sinensis is endemic, early screening and diagnosis of C. sinensis infection is crucial to prevent complications and interrupt the chain of transmission. Testing for C. sinensis IgG antibodies is frequently employed as a screening method for detecting the disease. However, its effectiveness in populations with a high risk remains to be determined. This study aimed to evaluate the clinical value of IgG antibody testing for screening C. sinensis infection in high-risk populations. Methods: Between October 2020 and September 2023, 1,080 participants from Liuzhou Municipal Liutie Central Hospital patients were recruited. All participants underwent enzyme-linked immunosorbent assay (ELISA) to detect IgG antibodies and fecal examination for C. sinensis eggs using the Kato-Katz technique. The study examined the diagnostic concordance between two methods by using inter-rater agreement evaluation (Kappa). The diagnostic effectiveness of IgG antibodies was assessed comprehensively and across different gender and age categories, with the outcomes of the parasite egg test serving as the benchmark for diagnosis. Results: Out of the 1,080 participants, 48.0% (518/1,080) tested positive for C. sinensis eggs, and 46.9% (506/1,080) tested positive for IgG antibodies. The Kappa value of the two methods' diagnostic concordance was 0.599. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of IgG antibody detection were 78.0%, 81.9%, 79.8%, 80.1%, and 80.0%, respectively, using C. sinensis eggs as the diagnostic criterion. Gender and age subgroup analyses revealed that diagnostic specificity, negative predictive value (NPV), and accuracy were higher in females than males (p = 0.003, 0.001, and 0.049, respectively). Sensitivity tended to decrease, while specificity tended to increase with age (p = 0.007 and 0.010, respectively). Conclusions: The technique for detecting Clonorchiasis IgG antibodies has a certain degree of accuracy in diagnosing C. sinensis, but its sensitivity is low, particularly in mild infections and in the elderly population. Diagnosis requires a combination of other assays or further optimization of the technique's performance. [ABSTRACT FROM AUTHOR]

High levels of pre-existing antibodies are amajor challenge for the application of viral vectors since they can severely limit their efficacy. To identify promising candidates among adeno-associated virus (AAV) based vectors for future gene therapies for the treatment of hereditary neuromuscular disorders (NMDs), we investigated the antibody levels in sera from patients with NMDs against 18 AAV types, including 11 AAVs with wild-type capsids, 5 AAVs with peptide-modified capsids and 2 AAVs with shuffled capsids. With regard to the wild-type capsid AAVs, the lowest binding antibody levels were detected against AAV6, AAV5, AAV12 and AAV9, whereas the highest binding antibody levels were detected against AAV10, AAV8, AAV1, and AAV2. The lowest neutralizing antibody levels againstwild-type AAVs were detected against AAV12, AAV5, AAV9, AAV7, AAV8 and AAV10, and the highest neutralizing antibody levels were detected against AAV13, AAV2 and AAV3. Interestingly, the influence of peptide modifications or shuffling of AAV capsids on antibody binding and AAV neutralization seemed to depend on the parental AAV. While the sex of the serum donors had no significant impact on binding or neutralizing antibody levels, we observed a trend to higher binding antibodies in older serum donors against some AAV types and a clear positive correlation of neutralizing antibody titers with the age of the serum donors. The disease status on the other hand did not have a meaningful impact on antibody levels, with no changes in AAV neutralization. Our data indicate that several wild-type or peptide-modified AAV may be good candidates for therapeutic application due to low pre-existing antibody levels, and that the age of potential recipients rather than their health status with regard to NMDs has the biggest impact on vector applicability. [ABSTRACT FROM AUTHOR]

Context In the previous issue of this journal, we reported that the incidence of fulminant type 1 diabetes (FT1D) due to the drug-induced hypersensitivity syndrome (DIHS) in Japan is higher than that in the general population and is associated with HLAB62. On the other hand, the reactivation of human herpesvirus 6 (HHV-6), which has been reported to be associated with DIHS, was observed at a higher frequency, but its association with the development of FT1D was unclear. Objective We aimed to clarify the relationship between the onset of FT1D and the reactivation of HHV-6. Methods We conducted a literature search for cases of DIHS-induced FT1D in addition to previously reported cases and investigated the changes in the HHV-6 antibody titer before and after the onset of FT1D. Results The HHV-6 antibody titer was increased just before or after the onset of FT1D in all 8 cases. In 1 case, HHV-6 DNA was also identified shortly before the onset of FT1D. Conclusion These results indicate for the first time that the reactivation of HHV-6 is associated with the onset of FT1D caused by DIHS. [ABSTRACT FROM AUTHOR]

Background: A sharp increase in reported brucellosis incidence was observed in northwestern Tajikistan (from 1.0/100,000 people in January-May 2022 to 32.7/100,000 in January-May 2023). Most (82%) cases were from the same remote mountainous village (population = 10,712). The aim of this study was to identify risk factors for brucellosis infection and mitigate disease risk. Methods: Using a case-control design, we conducted face-to-face interviews and collected blood samples during May-June 2023. Fifty-seven cases and 114 controls were recruited. Cases were the first person in a household diagnosed with brucellosis during February-June 2023 with positive serum agglutination test and antibody titers ≥1/160 from blood samples. Two controls were selected for each case (neighbors from different households matched by age and sex). Controls testing positive were excluded and replaced. We conducted conditional multivariable logistic regression to calculate adjusted odds ratio (AOR) and 95% confidence intervals (CI). Results: Among the 87 brucellosis patients reported, 57 (66%) agreed to participate and didn't have secondary cases in the household. Of the 57 cases, 68% were 15-44 years old, and 44% were male. Cases peaked in May 2023. Common symptoms were joint pain (95%), fever (84%), weakness (72%), and night sweats (65%). Of selected controls, 13% tested positive and were excluded. All cases and 94% of controls owned livestock (mostly cattle, sheep, or goats); no animals had not been vaccinated in the past 5 years. Brucellosis was associated with consumption of both homemade kaymak (clotted cream) and home-raised meat compared with neither (AOR: 59 [95%CI: 4.3-798], p < 0.01), home-raised meat but not kaymak compared with neither (AOR: 54 [4.0-731], p < 0.01), and involvement in animal slaughter compared with no involvement (AOR: 36 [2.8-461], p<0.01). Conclusion: Contact with unvaccinated livestock or consumption of their products was a key contributor to this outbreak in a remote village of Tajikistan. With 13% of controls testing positive, true incidence was likely greater than reported. Following our investigation, a brucellosis awareness education campaign and animal vaccination campaigns were carried out in the region and only one case was reported in September 2023. [ABSTRACT FROM AUTHOR]

Background: Understanding how infectious disease transmission varies from person to person, including associations with age and contact behavior, can help design effective control strategies. Within households, transmission may be highly variable because of differing transmission risks by age, household size, and individual contagiousness. Our aim was to disentangle those factors by fitting mathematical models to SARS-CoV-2 household survey and serologic data. Methods: We surveyed members of 3,381 Utah households from January-April 2021 and performed SARS-CoV-2 antibody testing on all available members. We paired these data with a probabilistic model of household importation and transmission composed of a novel combination of transmission variability and age- and size-structured heterogeneity. We calculated maximum likelihood estimates of mean and variability of household transmission probability between household members in different age groups and different household sizes, simultaneously with importation probability and probabilities of false negative and false positive test results. Results: 12.8% of individual participants, residing in 17.4% of the participating households, showed serologic evidence of prior infection or reported a prior positive test on the survey. Serologically positive individuals in younger age groups were less likely than older adults to have tested positive during their infection according to our survey results. Our model results suggested that adolescents and young adults (ages 13–24) acquired SARS-CoV-2 infection outside the household at a rate substantially higher than younger children and older adults. Our estimate of the household secondary attack rate (HSAR) among adults aged 45 and older exceeded HSARs to and/or from younger age groups at a given household size. We found lower HSAR in households with more members, independent of age differences. The age-specific HSAR patterns we found could not be explained by age-dependent biological susceptibility and transmissibility alone, suggesting that age groups contacted each other at different rates within households. Conclusions: We disentangled several factors contributing to age-specific infection risk, including non-household exposure, within-household exposure to specific age groups, and household size. Within-household contact rate differences played a significant role in driving household transmission epidemiology. These findings provide nuanced insights for understanding community outbreak patterns and mechanisms of differential infection risk. [ABSTRACT FROM AUTHOR]

Lassa virus (LASV) outbreaks in West Africa pose a significant public health threat. We investigated the infection phenotype and transmission (horizontal and vertical) of LASV strain Ba366 in its natural host, Mastomys natalensis. Here we analyze viral RNA levels in body fluids, virus titers in organs and antibody presence in blood. In adults and 2-week-old animals, LASV causes transient infections with subsequent seroconversion. However, mice younger than two weeks exhibit persistent infections lasting up to 16 months despite antibody presence. LASV can be detected in various body fluids, organs, and cell types, primarily in lung, kidney, and gonadal epithelial cells. Despite the systemic virus presence, no pathological alterations in organs are observed. Infected animals efficiently transmit the virus throughout their lives. Our findings underscore the crucial role of persistently infected individuals, particularly infected females and their progeny, in LASV dissemination within the host population. Mastomys natalensis, a mouse found closely to rural human dwellings in Sub-Saharan Africa, is a major reservoir for Lassa Virus (LASV). Here, the authors show that LASV causes transient infections in adult M. natalensis, but persistent infections in young animals despite antibodies. LASV is found in various organs without causing pathology and infected animals efficiently transmit the virus. [ABSTRACT FROM AUTHOR]

COVID-19 convalescent plasma (CCP) was one of the first therapies to receive emergency use authorization for management of COVID-19. We assessed the effectiveness of CCP in a propensity-matched analysis, and whether the presence of antibodies in the recipient at the time of treatment or the titer of antibodies in the administered CCP influenced clinical effectiveness. In an inpatient population within a single large health system, a total of 290 CCP patients were matched to 290 controls. While CCP increased titers of anti-SARS-CoV-2 RBD IgG titers post-CCP (p = <0.0001), no differences in 30-day survival were observed between CCP patients and controls in univariate and multivariate analyses. Survival at 30 days was numerically lower in recipients who were seronegative prior to CCP administration, compared to those with low titer and high titer anti-SARS-CoV-2 RBD IgG, respectively, but did not reach statistical significance (56% vs 82% vs 75%, p = 0.16). Patients who received 2 units of high-titer CCP had numerically better survival versus those who received fewer high-titer units, but this was not statistically significant (p = 0.08). CCP did not improve 30-day survival compared to propensity matched controls. Together these data support that CCP therapy provides limited benefit to hospitalized patients with SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion We have previously reported the mid‐term efficacy and safety of tacrolimus (Tac)‐based immunosuppressive therapy in such patients, and herein, we aimed to determine their long‐term outcomes (over 10 years).We retrospectively evaluate the data of 13 consecutive patients with biopsy‐proven long‐standing LN who underwent a long‐term Tac‐based treatment regimen. Tac was administered once daily at a dose of 3 mg as reinduction or maintenance treatment. Treatment outcomes were defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), urinary protein/creatinine ratio (Up/cr), serum creatinine, estimated glomerular filtration rate (eGFR) and serological lupus markers (complement C3, complement hemolytic activity [CH 50], and anti‐dsDNA antibody titre), and the concomitantly administered prednisolone (PDN) dose. Data on clinical parameters and serological lupus activity were collected annually from each patient throughout the study period.The patients' baseline characteristics at the treatment initiation were as follows: mean age, 18 years; Up/cr, 0.63 ± 0.69; serum C3 level, 57.2 ± 22.4 mg/dL (normal range, 79–152 mg/dL); CH50, 27.9 ± 15.7 U/mL (normal range, 23.0–46.0 U/mL); serum anti‐dsDNA antibody titre, 111.7 ± 123.4 IU/mL (normal range, <12.0 IU/mL); serum creatinine, 0.60 ± 0.19 mg/dL; eGFR, 115.6 ± 21.3 mL/min and SLEDAI, 13 ± 8.1. Despite the gradual tapering of the concomitantly administered PDN dose from 18.7 ± 13.5 mg/day at baseline to 3.5 ± 2.8 mg/day at 10 years (p = .002), a marked improvement in the outcomes, compared with the baseline values, was observed within a year. Additionally, these favourable changes persisted throughout study period in most patients. Compared with the baseline values, the following measures confirmed sustained outcome improvements after a 10‐year treatment: SLEDAI, 1.7 ± 2.0; serum C3 level, 83.8 ± 16.1 mg/dL; CH50, 45.6 ± 10.9 U/mL (all p < .01) and Up/cr, 0.16 ± 0.18 and serum anti‐dsDNA antibody titre, 25.8 ± 28.8 IU/mL (both p < .05). Serum creatinine level and eGFR remained within the normal range in all study participants except for one patient who experienced several flare‐ups. No serious adverse effects were observed.Our results suggest that long‐term Tac‐based immunosuppressive treatment as maintenance therapy is beneficial and has low cytotoxicity. Therefore, it represents an attractive option for the treatment of selected patients with paediatric‐onset LN in a real‐world setting. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune nodopathy (AN) is a new entity in the field of peripheral neuropathies and is defined by the presence of auto-antibodies against structures of the node of Ranvier combined with specific clinicopathophysiological features and therapy response in affected patients. The target-specific antibodies do not only serve as diagnostic biomarkers but also for treatment evaluation during follow-up. Case report: We report a 66-year-old female patient with various autoimmune diseases, including a history of membranous glomerulonephritis which presented with acute-onset, sensorimotor tetraparesis, cranial nerve involvement, and mild respiratory insufficiency. Under the suspicion of Guillain--Barreé syndrome, she received intravenous immunoglobulins (IVIg) and achieved remission. At 8 months later, she relapsed with now a poor response to IVIg and developed additional features such as severe sensory ataxia, tremor, and neuropathic pain. Anti-contactin-1 IgG2 antibodies were detected, and the diagnosis was reverted to AN. Plasma exchange and rituximab treatment led to a serological remission and corresponding significant clinical improvement, and the therapy was paused. At 2 years after symptom onset, her condition worsened again with sensorimotor symptoms and severe neuropathic pain despite seronegativity for contactin-1. However, serum binding assays to teased nerve fiber staining showed recurring antibody reactivity against paranodal structures. Caspr-1 was identified as a new target antigen via cell-based assay, and high-titer antibodies of the IgG4 subclass were confirmed via ELISA. Hence, a new cycle of plasma exchange and regular rituximab treatment was initiated, with subsequent clinical improvement and serological remission. The serum neurofilament light chain (sNFL) levels were assessed retrospectively and rose and fell together with the antibody titer. Discussion: This case demonstrates that autoimmunity to (para)nodal structures can reoccur especially in patients prone to autoimmune disorders and can switch its target antigen and subclass in the course of disease. The presence of autoantibodies against different targets at the node of Ranvier has direct implications for therapeutic management. We suggest a close follow-up of patients with AN after successful therapy. In case of deterioration despite seronegativity, nonspecific tests such as teased fiber assays and repeated screening for different target antigens should be considered. [ABSTRACT FROM AUTHOR]

Simple Summary: This present study evaluated the efficacy of dietary benzoic acid (BA) and oregano essential oil (OEO) separately or together as a substitute for a commercial coccidiostatic drug (salinomycin) on growth performance and physiological and immunological responses in broiler chickens challenged with Eimeria species. It was found that the BA and OEO applied alone or in combination significantly reduced gut pathogenic bacteria (Salmonella and Escherichia coli) and Eimeria spp. and concurrently enhanced the Lactobacillus population with better body weight gain, improved feed utilization, and superior hematological values. It boosted the immune system by enhancing Eimeria-specific immunoglobulin Y titer and up- and down-regulated various immune gene expressions to protect the chickens from inflammatory reactions that were not demonstrated in salinomycin-treated birds. This study suggests that the combined application of OEO and BA can substitute for salinomycin in controlling coccidiosis as well as improving growth performance, gut health, and immune responses in broiler chickens. To overcome the antimicrobial residues in food, benzoic acid (BA) and oregano essential oil (OEO) are used in the broiler chicken industry. Independently, both exerted anticoccidial and antimicrobial actions and improved growth performance in broiler chickens. Their effect may be multiplied when they are used in combination. This present study was carried out to evaluate the efficacy of dietary BA and OEO alone or in combination as a substitute for a commercial coccidiostatic drug on growth performance and physiological and immunological responses in broiler chickens challenged with Eimeria species. A total of 252 unsexed 1-day-old broiler chicks were equally allotted to 36 pens, each pen containing seven chicks. The pens were randomly assigned to six treatments with six pens (replicates) for each treatment (n = 6)—(i) negative control, (ii) positive control, coccidia-challenged and non-treated, (iii) supplemented with salinomycin (an anti-coccidial drug) at 60 mg/kg of feed and coccidia-challenged, (iv) supplemented with BA at 500 mg/kg of feed and coccidia-challenged, (v) supplemented with OEOat 500 mg/kg of feed and coccidia-challenged (OEO), and (vi) supplemented with BA at 500 mg/kg of feed and OEO at 500 mg/kg of feed and coccidia-challenged (B&O). The liver enzymes and thyroxine and creatinine levels were not affected (p > 0.05) both in coccidia-challenged and supplemented chickens. The BA and OEO applied separately or in combination (B&O) significantly (p < 0.05) reduced gut pathogenic bacteria (Salmonella and Escherichia coli) and Eimeria spp., and concurrently enhanced (p > 0.05) the Lactobacillus population with better body weight gain, improved feed utilization, and superior hematological values. It also up-regulated (p > 0.05) the interferon-γ gene expression and down-regulated (p < 0.05) the interleukin-10 and Toll-like receptor-4 gene expression to protect the chickens from inflammatory reactions, which were not demonstrated in salinomycin-treated birds. The B&O supplementation increased (p < 0.05) the immune system by enhancing Eimeria-specific immunoglobulin Y titer and lymphocyte proliferation response. This study suggests that the combined application of OEO and BA can substitute for a commercial anti-coccidial agent (salinomycin) in controlling coccidiosis as well as improving growth performance, gut health, and immune responses in broiler chickens with a means of antimicrobial-resistant free food products. [ABSTRACT FROM AUTHOR]

In this study, we developed an injectable DNA vaccine targeting the aopB gene of Aeromonas hydrophila, encapsulated within poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles, for use in common carp. Juvenile common carp were divided into six groups with three replicates each. Groups A and B received intramuscular injections of the plasmid containing the target gene (pCDNA3.1‐aopB) with or without encapsulation, respectively. Groups C and D received the plasmid lacking the target gene via the same route. Group E received PLGA, while Group F (control) received phosphate‐buffered saline. Sampling occurred on days 0, 30, and 60, and hematological and immunological indices were compared among the groups. On day 60, all groups were challenged with Aeromonas hydrophila, and cumulative mortality rates were assessed. Our results indicated successful detection of the target gene in various tissues of vaccinated fish. Notably, vaccinated groups exhibited a significant decrease in cumulative mortality (p < 0.05). Immunological indices, such as serum antibody titer and nonspecific immune responses, significantly improved in vaccinated groups, particularly those receiving the DNA vaccine with PLGA encapsulation (p < 0.05). Overall, the DNA vaccine, especially when nanoencapsulated with PLGA, demonstrated efficacy and immunogenicity against A. Hydrophila in common carp, suggesting its potential as a vaccination strategy against this infection. Further research could optimize its effectiveness and applicability. [ABSTRACT FROM AUTHOR]

Introduction: The gut microbiome is recognized as a factor that could potentially contribute to the persistent antibodies of antiphospholipid syndrome (APS). Gut microbial interventions can both induce and mitigate APS in mice. In human APS patients, anti-beta-2-glycoprotein I (β2GP-1) titers correlate with antibody titers against a gut commensal protein homologous to β2GP-1. Aim: To investigate the effect of the intestinal microenvironment on human APS. Methods We cross-sectionally compared intestinal microbiota composition quantified by shotgun sequencing; fecal short chain fatty acids (SCFAs), bacterial metabolites known to affect autoimmune processes; and fecal calprotectin, an intestinal inflammatory marker, in APS patients and healthy controls. Results: Neither alpha nor beta diversity of the gut microbiota differed between APS patients (n = 15) and controls (n = 16) and no taxa were differentially abundant. Moreover, fecal SCFAs and fecal calprotectin, did not differ between the groups. Conclusion: Gut microbiome effects on the APS phenotype are likely not driven by bacterial overabundance, SCFA production or intestinal inflammation. [ABSTRACT FROM AUTHOR]

Background: There is a dire need for the establishment of active dengue surveillance to continuously detect cases, circulating serotypes, and determine the disease burden of dengue fever (DF) in the country and region. Predicting dengue PCR results using machine learning (ML) models represents a significant advancement in pre‐emptive healthcare measures. This study outlines the comprehensive process of data preprocessing, model selection, and the underlying mechanisms of each algorithm employed to accurately predict dengue PCR outcomes. Methods: We analyzed data from 300 suspected dengue patients in Islamabad and Rawalpindi, Pakistan, from August to October 2023. NS1 antigen ELISA, IgM and IgG antibody tests, and serotype‐specific real‐time polymerase chain reaction (RT‐PCR) were used to detect the dengue virus (DENV). Representative PCR‐positive samples were sequenced by Sanger sequencing to confirm the circulation of various dengue serotypes. Demographic information, serological test results, and hematological parameters were used as inputs to the ML models, with the dengue PCR result serving as the output to be predicted. The models used were logistic regression, XGBoost, LightGBM, random forest, support vector machine (SVM), and CatBoost. Results: Of the 300 patients, 184 (61.33%) were PCR positive. Among the total positive cases detected by PCR, 9 (4.89%), 171 (92.93%), and 4 (2.17%) were infected with serotypes 1, 2, and 3, respectively. A total of 147 (79.89%) males and 37 (20.11%) females were infected, with a mean age of 33 ± 16 years. In addition, the mean platelet and leukocyte counts and the hematocrit percentages were 75,447%, 4189.02%, and 46.05%, respectively. The SVM was the best‐performing ML model for predicting RT‐PCR results, with 71.4% accuracy, 97.4% recall, and 71.6% precision. Hyperparameter tuning improved the recall to 100%. Conclusion: Our study documents three circulating serotypes in the capital territory of Pakistan and highlights that the SVM outperformed other models, potentially serving as a valuable tool in clinical settings to aid in the rapid diagnosis of DF. [ABSTRACT FROM AUTHOR]

Purpose: Nocardia is emerging as a common and easily neglected cause of both healthcare- and occupation-associated infections worldwide, however, human vaccines for Nocardia prevention are not yet available. In this study, we aimed to evaluate the immunoprotective effect of the NFA47630 protein, a secreted protein abundant in the N. farcinica IFM10152 supernatant. Methods: Conservation and characteristics of nfa47630 were analyzed by PCR and bioinformatics. Then recombinant NFA47630 protein was cloned, expressed and purified for further antigenicity analysis. Subsequently, the ability to activate innate immunity was evaluated by examining the phosphorylation status of the MAPK signaling pathway and cytokine levels. Finally, the protective effect was evaluated on rNFA47630-immunized mice. Results: nfa47630 was conserved in N. farcinica strains with good antigenicity. The rNFA47630 protein was expressed under the optimal conditions of 0.2 mM IPTG, 28 °C, and it can be recognized by anti-N. farcinica and anti-N. cyriacigeorgica sera, but not anti-N. asteroids, anti-N. brasiliensis, anti-N. nova and anti-Mycobacterium bovis sera. It can upregulate the phosphorylation status of ERK, JNK, P38 and the cytokine levels of TNF-α, IL-10, IL-12, and IFN-γ. In addition, mice immunized with rNFA47630 protein exhibited higher antibody titers, greater bacterial clearance ability, milder organ infection, and higher survival rates than PBS-immunized mice. Conclusions: Our data demonstrate that NFA47630 is a potential vaccine candidate for defending against N. farcinica infection. [ABSTRACT FROM AUTHOR]

Erysipelas still causes large economic losses to pig industry. Maternal immunity is critical to prevent erysipelas in young animals, thus, intensive vaccination protocols or practices focused on the improvement of the maternally derived immunity could provide substantial benefits. The present study evaluates potential changes in antibodies levels in sows and their offspring using two types of tests (commercial ELISA, Ingenasa or rSpaA415 ELISA) when two different vaccination programs (before farrowing or after farrowing) against Erysipelothrix rhusiopathiae were applied to sows from Iberian (A) or conventional Large White-Landrace (B) pig farms. The results showed a statistical correlation between titers found in sows and their one-week old piglets in both tests. The overall mean of (log) antibody titers in farm B measured by the commercial ELISA test was significantly higher in pre-farrowing vaccinated sows compared to the post-farrowing vaccine protocol (p = 0.0278). Additionally, using the rSpaA415 ELISA test, the overall mean of (log) antibody titers was significantly higher in pre-farrowing sows (p = 0.0056) compared to sows following post-farrowing vaccine protocol (p = 0.0003) or non- vaccinated sows. None of the above-mentioned differences were found in farm A. The overall mean of (log) antibody titers in piglets from the pre-farrowing vaccination protocol was significantly higher than piglets from the post-farrowing vaccination protocol in farm A (p = 0.0059; rSpaA415 ELISA) and farm B (p = 0.0168 and p = 0.0098 for the commercial and rSpaA415 ELISA data, respectively). Additionally, higher proportion of piglets from pre-farrowing vaccinated sows remained seropositive during the post-weaning period (days 42 to 84) compared to piglets from non-vaccinated or post-farrowing vaccinated groups in both farms A and B. [ABSTRACT FROM AUTHOR]

Background: Before SARS-CoV-2 vaccination availability, medical center employees were at high risk of COVID-19. However, risk factors for SARS-CoV-2 infection in medical center employees, both healthcare and non-healthcare workers, are poorly understood. Methods: From September-December 2020, free IgG antibody testing was offered to all employees at a large urban medical center. Participants were asked to complete a questionnaire on work and non-work related risk factors for COVID-19 infection. Results: SARS-CoV-2 seropositivity was found in 4.7%. Seropositivity was associated with close contact with COVID-19 cases with or without the use of adequate personal protective equipment (PPE), (OR 3.1 [95% CI 1.4–6.9] and OR 4.7 [95% CI 2.0–11.0] respectively), never wearing a mask outside of work (OR 10.1 [95% CI 1.9–57]), and Native Hawaiian/Pacific Islander race (OR 6.3 95% CI (1.6–25)]. Conclusions: Among workers in a large urban medical center, SARS-CoV-2 seropositivity was associated with work-related COVID-19 close contacts and low mask use outside of work, suggesting that non-workplace close contacts are also relevant routes of COVID-19 spread among healthcare workers. [ABSTRACT FROM AUTHOR]

Unlike most other picornaviruses, foot-and-mouth disease (FMD) intact virions (146S) dissociate easily into small pentameric subunits (12S). This causes a dramatically decreased immunogenicity by a mechanism that remains elusive. Here, we present the high-resolution structures of 12S (3.2 Å) and its immune complex of a single-domain antibody (VHH) targeting the particle interior (3.2 Å), as well as two 146S-specific VHHs complexed to distinct sites on the 146S capsid surface (3.6 Å and 2.9 Å). The antigenic landscape of 146S is depicted using 13 known FMD virus-antibody complexes. Comparison of the immunogenicity of 146S and 12S in pigs, focusing on the resulting antigenic sites and incorporating structural analysis, reveals that dissociation of 146S leads to structural alteration and destruction of multiple epitopes, resulting in significant differences in antibody profiles/lineages induced by 12S and 146S. Furthermore, 146S generates higher synergistic neutralizing antibody titers compared to 12S, whereas both particles induce similar total FMD virus specific antibody titers. This study can guide the structure-based rational design of novel multivalent and broad-spectrum recombinant vaccines for protection against FMD. Foot-and-mouth disease vaccine efficacy is reduced when full virion 146S dissociates into pentameric 12S subunit. Here, the authors elucidate the molecular basis of this compromised immunogenicity by comparing antigenicity, humoral immunogenicity and structures of 146S and 12S particles. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionCTRI Registration number\nSUMMARYWHO and other health agencies recommend that tetanus toxoid (TT) should be replaced by tetanus-diphtheria (Td) vaccine taking into consideration the low coverage and waning immunity, especially for diphtheria. In this randomised, multicentre, non-inferiority study, the immunogenicity and safety of TeddyVac™ vaccine of Human Biologicals Institute were compared with an existing brand.The study involved 444 eligible subjects in two age groups at four centres across India. Group A included subjects of 18–60 years and Group B subjects of 10–18 years of age. All subjects received single dose of either TeddyVac™ or the comparator vaccine as per randomisation. Blood samples for antibody titre estimation were collected before vaccination and 4–6 weeks after vaccination. Immunogenicity was assessed by estimating seroconversion rate, seroprotection rate, and geometric mean titres of antibodies. Safety was evaluated by collection and analysis of data on solicited and unsolicited adverse events.Overall, 441 subjects completed the study. Both the vaccine arms showed comparable seroconversion after a single dose for both the components. Both arms showed increase in seroprotection and geometric mean titres after a single dose of vaccination for both vaccine components, being significantly better for the diphtheria component in the test vaccine arm. Only few minor local and systemic adverse events were observed in both the vaccine arms. No serious adverse event was reported.The study results indicate that the TeddyVac™ vaccine is immunogenic, safe and non-inferior to the comparator Vaccine when administered to healthy subjects of 10 to 60 years of age.CTRI/2021/07/035112In a randomised, multicentre study, TeddyVac™ vaccine of Human Biologicals Institute was found to be immunogenic, safe and non-inferior to an existing commercial brand when administered to healthy subjects of 10 to 60 years of age. [ABSTRACT FROM AUTHOR]

Background: Serology (the detection of antibodies formed by the host against an infecting pathogen) is frequently used to assess current infections and past exposure to specific pathogens. However, the presence of cross-reactivity among host antibodies in serological data makes it challenging to interpret the patterns and draw reliable conclusions about the infecting pathogen or strain. Methodology/Principal findings: In our study, we use microscopic agglutination test (MAT) serological data from three host species [California sea lion (Zalophus californianus), island fox (Urocyon littoralis), and island spotted skunk (Spilogale gracilis)] with confirmed infections to assess differences in cross-reactivity by host species and diagnostic laboratory. All host species are known to be infected with the same serovar of Leptospira interrogans. We find that absolute and relative antibody titer magnitudes vary systematically across host species and diagnostic laboratories. Despite being infected by the same Leptospira serovar, three host species exhibit different cross-reactivity profiles to a 5-serovar diagnostic panel. We also observe that the cross-reactive antibody titer against a non-infecting serovar can remain detectable after the antibody titer against the infecting serovar declines below detectable levels. Conclusions/Significance: Cross-reactivity in serological data makes interpretation difficult and can lead to common pitfalls. Our results show that the highest antibody titer is not a reliable indicator of infecting serovar and highlight an intriguing role of host species in shaping reactivity patterns. On the other side, seronegativity against a given serovar does not rule out that serovar as the cause of infection. We show that titer magnitudes can be influenced by both host species and diagnostic laboratory, indicating that efforts to interpret absolute titers (e.g., as indicators of recent infection) must be calibrated to the system under study. Thus, we implore scientists and health officials using serological data for surveillance to interpret the data with caution. Author summary: Serology is frequently used for disease surveillance, especially in systems that are resource constrained or logistically challenging. Serological testing involves analyzing blood serum samples to detect antibodies with reactivity toward specific pathogens (or more generally, molecular antigens), with the goal of characterizing past exposure to those pathogens. However, these antibodies can be non-specific and may react against other related pathogens or strains–a phenomenon known as cross-reactivity. Interpretation of serological data exhibiting cross-reactivity is difficult and simplifying assumptions are often made (e.g., to interpret the strain that elicits the highest antibody titer level as the infecting pathogen strain). Our work shows that interpreting antibody data requires more nuance and more caution. Both absolute titers and relative reactivity against different strains can vary across host species and diagnostic laboratories, so it is essential to interpret these data in the appropriate context. These host species differences in antibody reactivity and cross-reactivity patterns make direct comparisons across species inadvisable. [ABSTRACT FROM AUTHOR]

We report the case of a 24-year-old previously healthy man who presented with an unusual combination of myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) and Leber’s hereditary optic neuropathy (LHON). Initially experiencing two episodes of painless visual acuity reduction, the patient responded well to glucocorticoid therapy, coinciding with an MOG antibody titre of 1:32. However, a subsequent third episode of painless vision loss did not improve with continued glucocorticoid treatment. Further diagnostic workup revealed a mitochondrial DNA mutation (11778 G>A), confirming the diagnosis of LHON. This unique presentation highlights the necessity of considering multiple aetiologies in cases of optic neuropathy where the cause is not immediately apparent, especially when the response to standard treatments is inconsistent. Our findings suggest that dual pathologies may coexist and should be considered in unexplained cases of optic neuropathy to facilitate appropriate clinical management. [ABSTRACT FROM AUTHOR]

Introduction: Molting is induced in commercial laying hens to rejuvenate the reproductive system and increase egg production. However, this process causes stress and reduces bird health and performance. Methods: The experiment was conducted to study the effect of multi probiotics and vitamin additives on induced molting in 240 ISA Brown hens. Hens were randomly divided into four groups receiving probiotic and vitamin additives (I-IV) during different period of molting. During the whole molting process, the laying performance indexes such as egg laying rate, egg quality, ovary weight and oviduct lengths were measured, and the spleen index, serum immunoglobulin, immune response of NDV and AIV vaccine were monitored. Results: Molted hens resumed 50% egg production in just 37 days, with 1.62% mortality. Egg quality such as egg weight, yolk color, Haugh unit, eggshell strength and protein height were significantly improved. After the second production peak, the reproductive organs and immune organs returned to normal, and the immune antibody titer of NDV vaccine increased significantly. Discussion: Molting with probiotic and vitamin additives improve the laying performance and egg quality, reduce mortality, significantly improve immune function and vaccine titer, and help to enhance disease resistance and maintain production performance of aged laying hens. [ABSTRACT FROM AUTHOR]

Idiopathic generalized tremor syndrome is a disorder characterized by an acute onset of full-body tremors, sometimes accompanied by vestibulo-cerebellar signs, that is responsive to treatment with corticosteroids. Although considered to have an overall good outcome, relapsing and persistent mild clinical signs have been described. So far, little is known about the etiopathology of this syndrome, but it is believed to have an immune-mediated origin. In human medicine, description of numerous autoantibodies involved in certain noninfectious neurologic disorders has revolutionized understanding of their pathophysiology, diagnosis and treatment. In this multicenter retrospective study, we aimed to describe the clinical signs, course, and outcome of dogs with idiopathic generalized tremor syndrome and correlate potential findings with the presence or absence of autoantibodies associated with autoimmune cerebellar syndromes in humans. Information regarding signalment, history, clinical signs, laboratory findings, diagnostic imaging and testing for regional infectious diseases was gathered and the remaining serum and CSF samples were then analyzed for neural antibodies against targets associated with autoimmune encephalitic diseases of humans. Thirty-three dogs were included, and screening for neural antibodies was performed in 30 of those dogs. The analysis showed an increased titer of mGluR1 antibodies in two dogs, GFAP and later in the course of disease mGluR1 antibodies in one dog and an increase in unspecific autoantibodies which could not be further classified in two dogs. Dogs with detectable neural autoantibodies always had cerebrospinal fluid abnormalities in the form of a pleocytosis, with or without increased protein concentration, and tended to present with hyperthermia, potentially indicating a more severe clinical form of idiopathic generalized tremor syndrome in these cases. In conclusion, idiopathic generalized tremor syndrome is proposed to be an immune-mediated disorder potentially mediated by neural autoantibodies in a subgroup of dogs. [ABSTRACT FROM AUTHOR]

Infectious laryngotracheitis (ILT) is a WOAH-listed respiratory disease in poultry caused by Gallid alphaherpesvirus 1, known as ILT virus (ILTV). We monitored two unvaccinated commercial layer flocks of 46- and 64-weeks old birds, more than 3 months after the onset of ILT. For this purpose, tracheal swabs, cloacal swabs, and blood samples were collected. Molecular and serology results were compared with the mortality data. The increased mortality in flocks 1 and 2 lasted 9 and 15 days, reaching 13.0% and 11.3%, respectively. We isolated the virus by inoculation on chicken embryo's chorioallantoic membrane. Tracheal swabs were positive at each sampling point, but cloacal swabs were negative. Based on the molecular and phylogenetic analysis of the ICP4 gene, the ILTV closely matched vaccine strains. In flock 1, seroconversion was evident at the second sampling (day 15). Thereafter, an increase in antibody titer was observed, eventually achieving levels that were nearly identical to those on day 15 and on 109. During the acute period of the outbreak, seroconversion was already visible in flock 2, and a similar pattern was then seen as in flock 1. Three months after the outbreak, the virus DNA was still persistently detected in tracheal swabs. [ABSTRACT FROM AUTHOR]

Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to assess the safety and exploratory efficacy of human umbilical cord-derived osteoblasts (hUC-Os), osteogenic differentiation-induced cells from hUCMSCs, in patients with early-stage ONFH. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 will be assigned to a low-dose (1 × 107 hUC-O cells, n = 3), medium-dose (2 × 107 cells, n = 3), and high-dose group (4 × 107 cells, n = 3) in the order of their arrival at the facility, and, depending on the occurrence of dose-limiting toxicity, up to 18 patients can be enrolled by applying the 3 + 3 escalation method. We will perform hUC-O (CF-M801) transplantation combined with core decompression and follow-up for 12 weeks according to the study protocol. Safety will be determined through adverse event assessment, laboratory tests including a panel reactive antibody test, vital sign assessment, physical examination, and electrocardiogram. Efficacy will be explored through the change in pain visual analog scale, Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index, ARCO stage, and also size and location of necrotic lesion according to Japanese Investigation Committee classification before and after the procedure. Joint preservation is important, particularly in younger, active patients with ONFH. Confirmation of the safety and efficacy of hUC-Os will lead to a further strategy to preserve joints for those suffering from ONFH and improve our current knowledge of cell therapy. [ABSTRACT FROM AUTHOR]

Background: While John Cunningham virus (JCV) is known to cause neuronal damage in progressive multifocal leukoencephalopathy (PML) among natalizumab-treated MS patients, its association with axonal loss in non-PML conditions remains unclear. Methods: In a cohort of 128 natalizumab-treated MS patients, serum neurofilament (sNfL) levels and JCV antibody titres were measured. Results: Among 128 patients (mean age = 38.4 years, 71.9% female), 51 (40%) were JCV positive. NfL levels increased by 15.3% for JCV index <0.7 (95% confidence interval [CI] = 0.963–1.381), by 18.6% for index 0.7–1.5 (95% CI = 1.009–1.394) and by 21.1% for index >1.5 (95% CI = 1.040–1.409) compared to JCV negative patients. Conclusion: These findings indicate a potential link between JCV burden and neuroaxonal degeneration in natalizumab-treated MS patients. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) is an important cause of chronic liver disease. Among at-risk populations, access to care is challenging. The French Ministry of Health has supported a seek-and-treat pilot intervention aiming at micro-elimination in Perpignan, France, to inform scale-up of elimination efforts across the whole territory. University College Dublin (UCD) led a successful EU funded project, called HepCare, focusing on the micro-elimination of HCV. UCD was contracted to evaluate and benchmark the Perpignan results against results from HepCare. Using mixed-method approaches including qualitative interviews with patients, a focus group with healthcare professionals, and quantitative analyses of the cascade of care against results obtained at other European sites, we analyse the acceptability, reproducibility, replicability, and effectiveness of the Perpignan intervention. A total of 960 participants were recruited in the Perpignan area. HCV antibody test results were obtained for 928 (96.6%), of which 150 (15.6%) were antibody-positive. Of the antibody-positive participants, 68 (45.3%) tested positive for HCV-RNA, 141 (94%) were linked to care, and of the HCV-RNA-positive participants, 60 (88%) started treatment. Of those who underwent treatment, 34 (56.7%) completed treatment and achieved a sustained viral response (SVR) at dataset closure, 18 (30%) were still in treatment, 5 (8.3%) defaulted from treatment, and 3 (5%) had a virologic failure or died. The intervention in Perpignan was acceptable to patients, but had limitations in effectiveness, as shown in comparisons with HepCare results. To engage harder-to-reach cohorts in France, future models of care in the territory should incorporate peer support. [ABSTRACT FROM AUTHOR]

The ISARIC 4C Mortality score was developed to predict mortality risk among patients with COVID-19. Its performance among vaccinated individuals is understudied. This is a retrospective study of all patients with SARS-CoV-2 infection admitted to the National Centre for Infectious Diseases, Singapore, from January-2020 to December-2021. Demographic, clinical, and laboratory data were extracted, and multiple logistic regression (MLR) models were developed to predict the relationship between ISARIC score, vaccination status, anti-S antibody titre, and severe COVID-19. A total of 6377 patients were identified, of which 5329 met the study eligibility criteria. The median age of the patients was 47 years (IQR 35–71), 1264 (23.7%) were female, and 1239 (25.7%) were vaccinated. Severe disease occurred in 499 (9.4%) patients, including 133 (2.5%) deaths. After stratification, 3.0% of patients with low (0–4), 17.8% of patients with moderate (5–9), and 36.2% of patients with high (≥10) ISARIC scores developed severe COVID-19. Vaccination was associated with a reduced risk of progression to severe COVID-19 in the MLR model: aOR 0.88 (95% CI: 0.86–0.90), and the risk of severe COVID-19 decreased inversely to anti-S antibody titres. The anti-S antibody titre should be further investigated as an adjunct to the ISARIC score to triage COVID-19 patients for hospital admission and antiviral therapy. [ABSTRACT FROM AUTHOR]

Adeno-associated viruses (AAV) are widely used as delivery vectors in clinical trials for in vivo gene therapy due to their unique features. Göttingen minipigs are a well-established animal model for several diseases and can be used for the efficacy and safety testing of AAV-based gene therapy. Pre-existing antibodies against AAV may influence the results of testing and, therefore, the animals should be tested for the presence of antibodies against relevant AAV serotypes. The detection of AAVs in pigs may be also important for the virus safety of xenotransplantation. In this study, we screened Göttingen minipigs from Ellegaard Göttingen Minipigs A/S, Denmark, and Marshall BioResources, USA, for antibodies against AAV1, AAV2, AAV6, AAV9 serotypes. Of the 20 animals tested, 18 had no neutralizing antibodies for all AAVs tested, none had antibodies against AAV9, only one had antibodies against AAV6, and the titers of antibodies against AAV1 and AAV2 were less than 1:100, with two exceptions. For total binding IgG, more individuals showed positivity for all the tested serotypes but, in general, the levels were low or zero. Three animals had no antibodies at all against the AAVs tested. Therefore, Göttingen minipigs could be considered an attractive animal model for gene therapy studies. Since some animals were negative for all AAVs tested, these may be selected and used as donor animals for xenotransplantation. [ABSTRACT FROM AUTHOR]

Pigeon paramyxovirus serotype 1 (PPMV-1), an antigenic and host variant of avian paramyxovirus Newcastle disease virus (NDV), primarily originating from racing pigeons, has become a global panzootic. Egypt uses both inactivated PPMV-1 and conventional NDV vaccines to protect pigeons from disease and mortality. However, the impact of prevalent strains and the effectiveness of available vaccines in pigeons in Egypt are unclear. This study investigates the virulence of PPMV-1 (Pigeon/Egypt/Sharkia-19/2015/KX580988) and evaluates available paramyxovirus vaccines in protecting pigeons against a PPMV-1 challenge. Ten-day-old specific-pathogen-free (SPF) embryonated chicken eggs infected with this strain exhibited a mean death time (MDT) of 86.4 ± 5.88 h. The intracerebral pathogenicity index (ICPI) in day-old chickens was 0.8, while pigeons experienced an ICPI of 0.96 and an intravenous pathogenicity index (IVPI) of 2.11. These findings classify the strain as virulent and velogenic. Experimental infection of pigeons with this PPMV-1 strain at 106 EID50/0.1 mL resulted in a 62.5% mortality rate, displaying nervous and enteric distress. The virus caused extensive lesions in visceral organs, with strong immunohistochemistry signals in all examined organs, indicating the systemic spread of the virus concurrent to its neurotropic and viscerotropic tropism. Furthermore, vaccination using an inactivated PPMV-1 and live NDV LaSota vaccine regimen protected 100% of pigeons against mortality, while with a single NDV LaSota vaccine, it was 62.5%. The PPMV alone or combined with NDV LaSota induced protective levels of haemagglutination inhibition (HI) antibody titres and reduced virus shedding from buccal and cloacal cavities. Based on generalised linear gamma model analysis, both PPMV-1 and NDV LaSota are antigenically comparable by HI. These findings suggest that using both inactivated PPMV-1 (G-VI) and live attenuated NDV (LaSota) vaccines is an effective prophylactic regimen for preventing and controlling PPMV-1 and NDV in pigeons, thereby reducing the risk of interspecies transmission. [ABSTRACT FROM AUTHOR]

The diagnostic accuracy of cerebrospinal fluid (CSF) anti-human T-cell leukemia virus type I (HTLV-1) antibody testing for HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM) remains unclear. Therefore, we measured the anti-HTLV-1 antibody levels in CSF using various test kits, evaluated the stability of CSF antibodies, and performed a correlation analysis using the particle agglutination (PA) method, as well as a receiver operating characteristic (ROC) analysis between patients with HAM and carriers. The CSF anti-HTLV-1 antibody levels were influenced by freeze–thaw cycles but remained stable when the CSF was refrigerated at 4 °C for up to 48 h. Measurements from 92 patients (69 patients with HAM and 23 carriers) demonstrated a strong correlation (r > 0.9) with the PA method across all six quantifiable test kits. All six test kits, along with CSF neopterin and CXCL10, exhibited areas under the ROC curve greater than 0.9, indicating a high diagnostic performance for HAM. Among these, five test kits, Lumipulse and Lumipulse Presto HTLV-I/II, HISCL-UD (a kit under development), HTLV-Abbott, and Elecsys HTLV-I/II, established a cutoff with 100% sensitivity and maximum specificity, achieving a sensitivity of 100% and a specificity ranging from 43.5% to 56.5%. This cutoff value, in combination with clinical findings, will aid in the accurate diagnosis of HAM. [ABSTRACT FROM AUTHOR]

Background Over the past 20 years, over 5 million cases of chikungunya, a mosquito-transmitted viral disease, have been reported in over 110 countries. Until recently, preventative strategies for chikungunya were largely ineffective, relying on vector control and individual avoidance of mosquito bites. Methods This review outlines the preclinical and clinical efficacy and safety data that led to the approval of VLA1553 (IXCHIQ®), a live-attenuated vaccine against chikungunya disease. It also describes the innovative development pathway of VLA1553, based on an immunological surrogate of protection, and discusses ongoing and future post-licensure studies. Results In mice and non-human primate models, VLA1553 elicited high titres of neutralizing antibodies, conferred protection against wild-type chikungunya virus challenge and raised no safety concerns. A Phase 1 clinical trial of VLA1553 demonstrated 100% seroconversion among 120 healthy participants, with sustained neutralizing antibody titres after 12 months. These results and determination of a surrogate marker of protection led to advancement of VLA1553 directly into Phase 3 clinical development, as agreed with the US Food and Drug Administration (FDA) and the European Medicines Agency. The pivotal Phase 3 trial met its primary immunogenicity endpoint, achieving seroprotective levels based on immuno-bridging in baseline seronegative participants 28 days post-vaccination. These findings enabled submission of a Biologics Licence Application to the FDA for accelerated approval of VLA1553 in the US for adults aged ≥18 years. Ongoing and planned studies will confirm the clinical efficacy/effectiveness and safety of VLA1553 in adults and younger individuals, and will generate data in chikungunya endemic countries that have the highest unmet need. Conclusion VLA1553 is the first vaccine approved for the prevention of chikungunya disease in adults, following accelerated development based on a serological surrogate marker of protection. VLA1553 adds to strategies to reduce the spread and burden of chikungunya in endemic populations and travellers. [ABSTRACT FROM AUTHOR]