Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials.

Background: The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

Methods: Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo.

Persistence and 4-year boosting of the bactericidal response elicited by two- and three-dose schedules of MenB-FHbp: A phase 3 extension study in adolescents.

Background: The period of heightened risk of invasive meningococcal disease in adolescence extends for >10 years. This study aimed to evaluate persistence of the immune response to the serogroup B meningococcal (MenB) vaccine MenB-FHbp (Trumenba, Bivalent rLP2086) under two- and three-dose primary vaccination schedules, both of which are approved in the United States and the European Union, and to assess safety and immunogenicity of a booster dose.

Methods: This was an open-label extension study of a phase 2 randomized MenB-FHbp study (primary study).

Implementing Universal Varicella Vaccination in Europe: The Path Forward.

Varicella is a common vaccine-preventable disease that usually presents as a mild disorder but can lead to severe complications. Before the implementation of universal varicella vaccination (UVV) in some European countries, the burden of varicella disease was broadly similar across the region. Despite this, countries adopted heterogeneous varicella vaccination strategies.

Efficacy, immunogenicity, and safety evaluation of an MF59-adjuvanted quadrivalent influenza virus vaccine compared with non-adjuvanted influenza vaccine in children: a multicentre, randomised controlled, observer-blinded, phase 3 trial.

Background: Young children have immature immune systems and respond poorly to standard influenza vaccines. The oil-in-water emulsion adjuvant MF59 can increase antigen uptake, macrophage recruitment, lymph node migration, and avidity to influenza virus. Therefore, we aimed to assess the relative efficacy, immunogenicity, and safety of an MF59-adjuvanted, quadrivalent, inactivated (subunit) influenza vaccine (aIIV4) compared with a US-licensed non-adjuvanted influenza vaccine in children.

Gene polymorphisms of fibronectin rs2289202 and fibrillin 2 rs331069 associate with vascular disease, the TAMRISK study.

Cell surface heparan sulfate (HS) proteoglycans interact with other extracellular matrix (ECM) components, and HS-binding regions are present in ECM proteins such as fibronectin and fibrillin. Because of their previously established role in susceptibility to intracranial aneurysms, the authors sought to determine whether polymorphisms of fibronectin (FN1, rs2289202) and fibrillin 2 (FBN2, rs331069) associate with selected cardiovascular risk factors and events in the TAMRISK study. A 50-year-old Finnish cohort of 810 subjects of whom 340 had diagnosed hypertension was analyzed.

A Bivalent Meningococcal B Vaccine in Adolescents and Young Adults.

Background: MenB-FHbp is a licensed meningococcal B vaccine targeting factor H-binding protein. Two phase 3 studies assessed the safety of the vaccine and its immunogenicity against diverse strains of group B meningococcus.

Methods: We randomly assigned 3596 adolescents (10 to 18 years of age) to receive MenB-FHbp or hepatitis A virus vaccine and saline and assigned 3304 young adults (18 to 25 years of age) to receive MenB-FHbp or saline at baseline, 2 months, and 6 months.

Report of the 5th European expert meeting on rotavirus vaccination (EEROVAC).

The Fifth European Expert Meeting on Rotavirus Vaccination was convened in Utrecht, The Netherlands, in March 2017. The 2-day meeting included invited lectures as well as original oral and poster presentations and brought together experts from 21 countries. Summary findings of the meeting include: Rotavirus vaccination programmes in Europe have resulted in reductions of 60-90% in rotavirus outpatient visits and hospitalizations.

Alemtuzumab Use in Clinical Practice: Recommendations from European Multiple Sclerosis Experts.

Alemtuzumab (Lemtrada™) is a humanized monoclonal antibody approved in more than 50 countries. Within the European Union, alemtuzumab is indicated for the treatment of adult patients with relapsing-remitting multiple sclerosis (RRMS) with active disease defined by clinical or imaging features; in the USA, the indication states that alemtuzumab should generally be reserved for the treatment of patients with relapsing forms of multiple sclerosis who have had an inadequate response to two or more disease-modifying therapies (DMTs). In clinical trials, alemtuzumab demonstrated efficacy in treatment-naïve patients with active RRMS and those relapsing on prior DMTs, with a consistent and manageable safety and tolerability profile.

Glucuronic Acid Epimerase (GLCE) Variant rs3865014 (A>G) Is Associated with BMI, Blood Hemoglobin, Hypertension, and Cerebrovascular Events, the TAMRISK Study.

Heparan sulfate proteoglycans modulate many physiological systems, and genes responsible for proteoglycan assembly and disassembly may affect their interaction. We sought to determine whether polymorphisms of the glucuronic acid epimerase (GLCE) rs3865014 and sulfatase-2 (SULF2) rs2281279, genes coding for enzymes participating in heparan sulfate side chain activity, associate with hypertension, selected cardiometabolic risk factors and cardiovascular events in the Tampere adult population cardiovascular risk study. A Finnish cohort of 339 subjects with diagnosed hypertension and 441 controls was analyzed.

Type-specific and cross-reactive antibodies and T cell responses in norovirus VLP immunized mice are targeted both to conserved and variable domains of capsid VP1 protein.

Norovirus (NoV)-specific antibodies, which block binding of the virus-like particles (VLPs) to the cell receptors are conformation dependent and directed towards the most exposed domain of the NoV capsid VP1 protein, the P2 domain. Limited data are available on the antibodies directed to other domains of the VP1, and even less on the NoV VP1-specific T cell epitopes. In here, BALB/c mice were immunized with six VLPs derived from NoV GII.

Safety and immunogenicity of an intramuscular quadrivalent influenza vaccine in children 3 to 8 y of age: A phase III randomized controlled study.

A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3-8 y of age (EudraCT no. 2011-005374-33).

Simple and efficient ultrafiltration method for purification of rotavirus VP6 oligomeric proteins.

Bacterial endotoxins, DNA, live viruses, and viral proteins derived from bacterial and baculovirus (BV) expression vectors employed in recombinant protein production contaminate the final product. Density gradient centrifugation is commonly used to partially purify oligomeric proteins, but impurities from the expression system still remain. We describe a simple and rapid ultrafiltration method for final purification of rotavirus VP6 oligomeric nanotubes and nanospheres.

Decorin Genotypes, Serum Glucose, Heart Rate, and Cerebrovascular Events: The Tampere Adult Population Cardiovascular Risk Study.

Background: Decorin is an extracellular matrix proteoglycan that may attenuate progression of atherosclerosis and its complications, such as stroke. Among its multitude of functions, decorin has been suggested to serve as a receptor for resistin, an adipokine involved in energy homeostasis. The GG genotype of the decorin polymorphism rs7308752 (A>G) and the CC genotype of the rs516115 (T>C) are associated with decreased plasma resistin levels.

Genetic Polymorphisms of Transcription Factor NRF2 and of its Host Gene Sulfiredoxin (SRXN1) are Associated with Cerebrovascular Disease in a Finnish Cohort, the TAMRISK Study.

Oxidative stress is involved in the pathophysiology of many cardiovascular disorders, such as hypertension and atherosclerosis. NRF2 is the primary transcriptional regulator of several antioxidant genes, including that of sulfiredoxin (SRXN1). The association of genotypes of NRF2 and SRXN1 with cardiovascular conditions was studied in a Finnish cohort of 336 subjects with diagnosed hypertension and 480 normotensive controls from the Tampere adult population cardiovascular risk study (TAMRISK).

Effectiveness of the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D-Conjugated Vaccine (PHiD-CV) Against Carriage and Acute Otitis Media-A Double-Blind Randomized Clinical Trial in Finland.

Unlabelled: After administering the 10-valent pneumococcal polysaccharide nontypeable Haemophilus influenzae protein D-conjugated vaccine (PHiD-CV) to children aged 2-18 months, we observed a reduction in vaccine-type nasopharyngeal carriage, resulting in a reduction of overall pneumococcal nasopharyngeal carriage, which may be important for indirect vaccine effects. We noted a trend toward reduction of acute otitis media.

Background: This trial (ClinicalTrials.

Assessment of Functional Norovirus Antibody Responses by Blocking Assay in Mice.

Norovirus (NoV)-specific serum antibodies bind to NoV-derived virus-like particles (VLPs) and block the binding of VLPs to the host cell attachment factors/receptors, histo-blood group antigens (HBGAs). Blocking antibodies in human sera have been associated with a protection from NoV infection and disease. Studies of experimental NoV VLP-based vaccines measure blocking antibodies in animal sera instead of a traditional virus neutralization assay.

Residential mobility and the risk of childhood leukemia.

Purpose: An infective origin of childhood leukemia has been postulated, with leukemia developing as a rare response to an infection. Population mixing can result in increased contacts between infected and susceptible individuals and may increase the risk of leukemia. The objective of this study was to investigate the association between residential mobility as an indicator of population mixing at individual level and the risk of leukemia in children (<15 years).

Immunogenicity, Safety, and Tolerability of Bivalent rLP2086 Meningococcal Group B Vaccine Administered Concomitantly With Diphtheria, Tetanus, and Acellular Pertussis and Inactivated Poliomyelitis Vaccines to Healthy Adolescents.

Key Points: Concomitant administration of bivalent rLP2086 (Trumenba [Pfizer, Inc] and diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) was immunologically noninferior to DTaP/IPV and saline and was safe and well tolerated. Bivalent rLP2086 elicited robust and broad bactericidal antibody responses to diverse Neisseria meningitidis serogroup B strains expressing antigens heterologous to vaccine antigens after 2 and 3 vaccinations.

Background: Bivalent rLP2086, a Neisseria meningitidis serogroup B (MnB) vaccine (Trumenba [Pfizer, Inc]) recently approved in the United States to prevent invasive MnB disease in individuals aged 10-25 years, contains recombinant subfamily A and B factor H binding proteins (fHBPs).

Immunogenicity, Safety and Antibody Persistence of a Booster Dose of Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine Compared with Monovalent Meningococcal Serogroup C Vaccine Administered Four Years After Primary Vaccination Using the Same Vaccines.

Background: We evaluated safety, immunogenicity and antibody persistence of meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) booster vaccination 4 years after priming of toddlers.

Methods: This phase III, open-label, controlled study in Finland (NCT00955682) enrolled children previously randomized (3:1) at 12-23 months (NCT00474266) to receive 1 dose of MenACWY-TT or MenC conjugate vaccine (MenC-CRM197). Serum bactericidal antibody titers using rabbit (rSBA, cut-off 1:8) and human complement (hSBA, cut-off 1:8) were assessed at year 3 and 4 after priming and 1 month and 1 year after administration of a booster dose of the same vaccine given for primary vaccination.

Development and maturation of norovirus antibodies in childhood.

The burden of norovirus (NoV) gastroenteritis is substantial in young children. Maternal antibodies are thought to protect a child from NoV infection in early infancy but subsequent development of NoV-specific protective immunity in children is still largely unexplored. We have determined NoV-specific antibody seroconversion to GII.

Functional Inducible Nitric Oxide Synthase Gene Variants Associate With Hypertension: A Case-Control Study in a Finnish Population-The TAMRISK Study.

Increased inducible nitric oxide synthase (iNOS) activity and expression has been associated with hypertension, but less is known whether the 2 known functional polymorphic sites in the iNOS gene (g.-1026 C/A (rs2779249), g.2087 G/A (rs2297518)) affect susceptibility to hypertension.

NLR family pyrin domain containing 3 (NLRP3) inflammasome gene polymorphism rs7512998 (C>T) predicts aging-related increase of blood pressure, the TAMRISK study.

Background: The activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome by cellular stress leads to activation of the inflammasome, and NLRP3 gene polymorphisms have been associated with autoinflammatory diseases. Inflammasomes have also been implicated in the initiation or progression of metabolic disorders such as atherosclerosis, type 2 diabetes and obesity. The association of NLRP3 genetic variant rs7512998 with blood pressure and hypertension was studied in a 50-year-old Finnish cohort with a subpopulation who had available data on blood pressure measurements also at the age of 45 years.

Rotavirus capsid VP6 protein acts as an adjuvant in vivo for norovirus virus-like particles in a combination vaccine.

Rotavirus (RV) and norovirus (NoV) are the 2 leading causes of acute viral gastroenteritis worldwide. We have developed a non-live NoV and RV vaccine candidate consisting of NoV virus-like particles (VLPs) and recombinant polymeric RV VP6 protein produced in baculovirus-insect cell expression system. Both components have been shown to induce strong potentially protective immune responses.

Meningococcal Serogroup B Bivalent rLP2086 Vaccine Elicits Broad and Robust Serum Bactericidal Responses in Healthy Adolescents.

Background: Neisseria meningitidis serogroup B (MnB) is a leading cause of invasive meningococcal disease in adolescents and young adults. A recombinant factor H binding protein (fHBP) vaccine (Trumenba(®); bivalent rLP2086) was recently approved in the United States in individuals aged 10-25 years. Immunogenicity and safety of 2- or 3-dose schedules of bivalent rLP2086 were assessed in adolescents.

Association of Zinc Finger, C3HC-Type Containing 1 (ZC3HC1) rs11556924 Genetic Variant With Hypertension in a Finnish Population, the TAMRISK Study.

In a recent genome-wide association study, the zinc finger, C3HC-type containing 1 (ZC3HC1) polymorphism was strongly associated with coronary artery disease (CAD) by an unknown mechanism. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related with CAD through low-density lipoprotein (LDL) metabolism. The association of both of the above genetic variants with hypertension was studied in a Finnish 50-year-old cohort.