Vaccination prevents severe COVID-19 outcome in patients with neutralizing type 1 interferon autoantibodies.

A hallmark of patients with autoimmune polyendocrine syndrome type 1 (APS-1) is serological neutralizing autoantibodies against type 1 interferons (IFN-I). The presence of these antibodies has been associated with severe course of COVID-19. The aims of this study were to investigate SARS-CoV-2 vaccine tolerability and immune responses in a large cohort of patients with APS-1 (N = 33) and how these vaccinated patients coped with subsequent infections.

Systemic interferon type I and B cell responses are impaired in autoimmune polyendocrine syndrome type 1.

Autoimmune polyendocrine syndrome type I (APS-1) is caused by mutations in the autoimmune regulator (AIRE) gene and characterised clinically by multiple autoimmune manifestations and serologically by autoantibodies against tissue proteins and cytokines. We here hypothesised that lack of AIRE expression in thymus affects blood immune cells and performed whole-blood microarray analysis (N = 16 APS-I patients vs 16 controls), qPCR verification, and bioinformatic deconvolution of cell subsets. We identified B cell responses as being downregulated in APS-1 patients, which was confirmed by qPCR; these results call for further studies on B cells in this disorder.

A conserved glutathione binding site in poliovirus is a target for antivirals and vaccine stabilisation.

Strategies to prevent the recurrence of poliovirus (PV) after eradication may utilise non-infectious, recombinant virus-like particle (VLP) vaccines. Despite clear advantages over inactivated or attenuated virus vaccines, instability of VLPs can compromise their immunogenicity. Glutathione (GSH), an important cellular reducing agent, is a crucial co-factor for the morphogenesis of enteroviruses, including PV.

GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A .

Group A (GAS) causes about 500,000 annual deaths globally, and no vaccines are currently available. The Group A Carbohydrate (GAC), conserved across all GAS serotypes, conjugated to an appropriate carrier protein, represents a promising vaccine candidate. Here, we explored the possibility to use Generalized Modules for Membrane Antigens (GMMA) as an alternative carrier system for GAC, exploiting their intrinsic adjuvant properties.

Recent Developments in Enteric Bacterial Vaccines.

In this issue, we present promising developments in the field of bacterial enteric vaccines [...

National control laboratory independent lot testing of COVID-19 vaccines: the UK experience.

The past 18 months have seen an unprecedented approach to vaccine development in the global effort against the COVID-19 pandemic. The process from discovery research, through clinical trials and regulatory approval often takes more than 10 years. However, the critical need to expedite vaccine availability in the pandemic has meant that new approaches to development, manufacturing, and regulation have been required: this has necessitated many stages of product development, clinical trials, and manufacturing to be undertaken in parallel at a global level.

Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component GMMA-Based Vaccines.

Generalised modules for membrane antigens (GMMA)-based vaccines comprise the outer membrane from genetically modified Gram-negative bacteria containing membrane proteins, phospholipids and lipopolysaccharides. Some lipoproteins and lipopolysaccharides are pyrogens; thus, GMMA-based vaccines are intrinsically pyrogenic. It is important to control the pyrogenic content of biological medicines, including vaccines, to prevent adverse reactions such as febrile responses.

International multicenter, multiplatform study to validate Taipan snake venom time as a lupus anticoagulant screening test with ecarin time as the confirmatory test: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

Background: Lupus anticoagulant (LA) assays are compromised in anticoagulated patients, and existing strategies to overcome the interferences have limitations. The prothrombin-activating Taipan snake venom time (TSVT) screening test and ecarin time (ET) confirmatory test are innately insensitive to vitamin K antagonists (VKA) and direct factor Xa inhibitors (DFXaI).

Objectives: Validate standardized TSVT/ET reagents for LA detection, in a multicenter, multiplatform study.

Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines.

Global vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV and IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome, represent safe next-generation vaccines, however their production requires optimisation. Here we present an efficient mammalian expression strategy producing good yields of wild-type PV VLPs for all three serotypes and a thermostabilised variant for PV3.

Three-Dimensional Human Alveolar Stem Cell Culture Models Reveal Infection Response to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the cause of a present pandemic, infects human lung alveolar type 2 (hAT2) cells. Characterizing pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hAT2 cells limits the study.

Animal testing for vaccines. Implementing replacement, reduction and refinement: challenges and priorities.

Transition to in vitro alternative methods from in vivo in vaccine release testing and characterization, the implementation of the consistency approach, and a drive towards international harmonization of regulatory requirements are most pressing needs in the field of vaccines. It is critical for global vaccine community to work together to secure effective progress towards animal welfare and to ensure that vaccines of ever higher quality can reach the populations in need in the shortest possible timeframe. Advancements in the field, case studies, and experiences from Low and Middle Income Countries (LMIC) were the topics discussed by an international gathering of experts during a recent conference titled "Animal Testing for Vaccines - Implementing Replacement, Reduction and Refinement: Challenges and Priorities".

Summary of the WHO hearing on the development of product-specific reference materials for coagulation factor VIII and factor IX products.

In recent years, several modified recombinant factor (F) VIII and FIX therapeutics with extended half-life have been licensed internationally for the treatment of haemophilia. Safe and effective use of these products requires monitoring of factor activity in patient plasma. The potency of all FVIII and FIX products is currently assigned in International Units (IU) which anchors the relationship between potency labelling, dosing and clinical monitoring.

Activity measurements of dalcinonacog alfa.

Introduction: Many recombinant and modified FIX products have been, and continue to be, developed with the aim of improving treatment for patients with haemophilia B. One such new product is dalcinonacog alfa, a recombinant FIX with modifications to provide improved features such as subcutaneous administration.

Aim: In view of previously observed assay discrepancies with modified FIX therapeutics, the aim of this study was to assess potential discrepancies in potency measurement of dalcinonacog alfa between and within different assay methods.

A European multicentre evaluation of detection and typing methods for human enteroviruses and parechoviruses using RNA transcripts.

Polymerase chain reaction (PCR) detection has become the gold standard for diagnosis and typing of enterovirus (EV) and human parechovirus (HPeV) infections. Its effectiveness depends critically on using the appropriate sample types and high assay sensitivity as viral loads in cerebrospinal fluid samples from meningitis and sepsis clinical presentation can be extremely low. This study evaluated the sensitivity and specificity of currently used commercial and in-house diagnostic and typing assays.

The impact of thioredoxin reduction of allosteric disulfide bonds on the therapeutic potential of monoclonal antibodies.

Therapeutic mAbs are used to manage a wide range of cancers and autoimmune disorders. However, mAb-based treatments are not always successful, highlighting the need for a better understanding of the factors influencing mAb efficacy. Increased levels of oxidative stress associated with several diseases are counteracted by the activities of various oxidoreductase enzymes, such as thioredoxin (Trx), which also reduces allosteric disulfide bonds in proteins, including mAbs.

Development and validation of a monocyte activation test for the control/safety testing of an OMV-based meningococcal B vaccine.

It is imperative to ensure biological products are free of contaminating pyrogenic material prior to administration to patients. Historically the rabbit pyrogen test (RPT) was used to screen for such contamination in medicines for intravenous delivery. This test was adapted for use to screen vaccines.

First Detection of Swedish' Variant (nvCT) in a Russian Couple with Infertility.

Background: Chronic asymptomatic chlamydial genital infection caused by the wild-type of (wtCT) is the most common bacterial infection causing human infertility. The novel 'Swedish' variant of (nvCT) which contains a 377 bp deletion in a region that is specifically targeted in some nucleic acid amplification tests may impede diagnosis.

Objective: The study aimed to investigate whether nvCT may be a possible cause of infertility in a couple undergoing fertilization (IVF).

Molecular characterization of human Sapovirus in untreated sewage in Italy by amplicon-based Sanger and next-generation sequencing.

Aims: Human Sapoviruses (HSaVs) are etiological agents of sporadic cases and outbreaks of acute gastroenteritis in humans of all ages. Evidence of worldwide distribution of HSaV has been documented; however, little is known about HSaV circulation in Italy. To study their occurrence and genetic diversity a nation-wide environmental surveillance was undertaken.

Correction to: Genetic Diversity Among Genogroup II Noroviruses and Progressive Emergence of GII.17 in Wastewaters in Italy (2011-2016) Revealed by Next-Generation and Sanger Sequencing.

The original version of this article unfortunately contained a mistake. The presentation of Table 1 was incorrect. The corrected table is given below.

Chitosan nanoparticle antigen uptake in epithelial monolayers can predict mucosal but not systemic in vivo immune response by oral delivery.

This study compared in vitro and in vivo antigen delivery effects of ultrapure chitosan (CS) chloride. CS nanoparticles were formulated to incorporate ovalbumin (OVA) as a model antigen and characterised for size, charge, OVA complexation and release. The effect of CS:OVA nanoparticles on cell viability, epithelial tight junctions and transepithelial permeation of OVA was tested on Caco-2 monolayer in vitro intestinal model.

Recommendations for enterovirus diagnostics and characterisation within and beyond Europe.

Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN).

Genetic Diversity Among Genogroup II Noroviruses and Progressive Emergence of GII.17 in Wastewaters in Italy (2011-2016) Revealed by Next-Generation and Sanger Sequencing.

Noroviruses (NoV) are a major cause of gastroenteritis worldwide. Recently, a novel variant of NoV GII.17 (GII.