Non-neutralizing antibody responses following A(H1N1)pdm09 influenza vaccination with or without AS03 adjuvant system.

Background: Non-neutralizing antibodies inducing complement-dependent lysis (CDL) and antibody-dependent cell-mediated cytotoxicity (ADCC) activity may contribute to protection against influenza infection. We investigated CDL and ADCC responses in healthy adults randomized to receive either non-adjuvanted or AS03-adjuvanted monovalent A(H1N1)pdm09 vaccine (containing 15 µg/3.75 μg of hemagglutinin, respectively) on a 2-dose schedule 21 days apart.

An automated segmentation approach to calibrating infantile nystagmus waveforms.

Infantile nystagmus (IN) describes a regular, repetitive movement of the eyes. A characteristic feature of each cycle of the IN eye movement waveform is a period in which the eyes are moving at minimal velocity. This so-called "foveation" period has long been considered the basis for the best vision in individuals with IN.

Spatial summation across the visual field in strabismic and anisometropic amblyopia.

Ricco's area (the largest area of visual space in which stimulus area and intensity are inversely proportional at threshold) has previously been hypothesised to be a result of centre/surround antagonism in retinal ganglion cell receptive fields, but recent evidence suggests a sizeable cortical contribution. Here, Ricco's area was measured in amblyopia, a condition in which retinal receptive fields are normal, to better understand its physiological basis. Spatial summation functions were determined at 12 visual field locations in both eyes of 14 amblyopic adults and 15 normal-sighted controls.

Induction of H7N9-Cross-Reactive Antibody-Dependent Cellular Cytotoxicity Antibodies by Human Seasonal Influenza A Viruses that are Directed Toward the Nucleoprotein.

Antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) against avian influenza virus subtypes, including H7N9 and H5N1, have been detected in human sera. Using NK cell activation and NK cytotoxicity assays, we compared ADCC-mediating antibodies (ADCC-Abs) in sera collected from healthy infants, children and adults against H7N9 virus-infected cells and recombinant hemagglutinin (HA), neuraminidase (NA), and nucleoprotein (NP) proteins. High titers of ADCC-Abs against H7N9 virus-infected cells were detected in sera from adults and children but not infants.

Both Neutralizing and Non-Neutralizing Human H7N9 Influenza Vaccine-Induced Monoclonal Antibodies Confer Protection.

Pathogenic H7N9 avian influenza viruses continue to represent a public health concern, and several candidate vaccines are currently being developed. It is vital to assess if protective antibodies are induced following vaccination and to characterize the diversity of epitopes targeted. Here we characterized the binding and functional properties of twelve H7-reactive human antibodies induced by a candidate A/Anhui/1/2013 (H7N9) vaccine.

Evaluation of Cardiac Involvement in Children with Dengue by Serial Echocardiographic Studies.

Background: Infection with dengue virus results in a wide range of clinical manifestations from dengue fever (DF), a self-limited febrile illness, to dengue hemorrhagic fever (DHF) which is characterized by plasma leakage and bleeding tendency. Although cardiac involvement has been reported in dengue, the incidence and the extent of cardiac involvement are not well defined.

Methods And Principal Findings: We characterized the incidence and changes in cardiac function in a prospective in-patient cohort of suspected dengue cases by serial echocardiography.

High Antibody-Dependent Cellular Cytotoxicity Antibody Titers to H5N1 and H7N9 Avian Influenza A Viruses in Healthy US Adults and Older Children.

Human influenza is a highly contagious acute respiratory illness that is responsible for significant morbidity and excess mortality worldwide. In addition to neutralizing antibodies, there are antibodies that bind to influenza virus-infected cells and mediate lysis of the infected cells by natural killer (NK) cells (antibody-dependent cellular cytotoxicity [ADCC]) or complement (complement-dependent lysis [CDL]). We analyzed sera obtained from 16 healthy adults (18-63 years of age), 52 children (2-17 years of age), and 10 infants (0.

Relationship of preexisting influenza hemagglutination inhibition, complement-dependent lytic, and antibody-dependent cellular cytotoxicity antibodies to the development of clinical illness in a prospective study of A(H1N1)pdm09 Influenza in children.

The hemagglutination inhibition (HAI) antibody titer is considered the primary immune correlate of protection for influenza. However, recent studies have highlighted the limitations on the use of the HAI titer as a correlate in at-risk populations such as children and older adults. In addition to the neutralization of cell-free virus by antibodies to hemagglutinin and interference of virus release from infected cells by antibodies to neuraminidase, influenza virus-specific antibodies specifically can bind to infected cells and lyse virus-infected cells through the activation of complement or natural killer (NK) cells, via antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent lysis (CDL).

Elucidating the role of T cells in protection against and pathogenesis of dengue virus infections.

Dengue viruses (DENV) cause significantly more human disease than any other arbovirus, with hundreds of thousands of cases leading to severe disease in thousands annually. Antibodies and T cells induced by primary infection with DENV have the potential for both positive (protective) and negative (pathological) effects during subsequent DENV infections. In this review, we summarize studies that have examined T-cell responses in humans following natural infection and vaccination.

Grating visual acuity in infantile nystagmus in the absence of image motion.

Purpose: Infantile nystagmus (IN) consists of largely horizontal oscillations of the eyes that usually begin shortly after birth. The condition is almost always associated with lower-than-normal visual acuity (VA). This is assumed to be at least partially due to motion blur induced by the eye movements.

Serological documentation of maternal influenza exposure and bipolar disorder in adult offspring.

Objective: The authors examined whether serologically confirmed maternal exposure to influenza was associated with an increased risk of bipolar disorder in the offspring and with subtypes of bipolar disorder, with and without psychotic features.

Method: The study used a nested case-control design in the Child Health and Development Study birth cohort. In all, 85 individuals with bipolar disorder were identified following extensive ascertainment and diagnostic assessment and matched to 170 comparison subjects in the analysis.

Stress and visual function in infantile nystagmus syndrome.

Purpose: Infantile nystagmus syndrome (INS) is an involuntary oscillation of the eyes that has been reported to impair vision and worsen under stress. This investigation aimed to measure visual function in terms of visual acuity (VA) and response time (RT), when INS subjects are placed under stress.

Methods: A total of 23 subjects with INS and 20 control subjects performed a 2-alternative forced choice (2AFC) staircase procedure identifying the gap in a Landolt C, under 4 experimental conditions: initial acclimatization (A); task demand (TD), during which subjects received a small electrical shock for every incorrect answer; anticipatory anxiety (AA), during which subjects received a small shock at random intervals; and relaxed (R).

Post-translational intracellular trafficking determines the type of immune response elicited by DNA vaccines expressing Gag antigen of Human Immunodeficiency Virus Type 1 (HIV-1).

In the current study, immune responses induced by Gag DNA vaccines with different designs were evaluated in Balb/C mice. The results demonstrated that the DNA vaccine with the full length wild type gag gene (Wt-Gag) mainly produced Gag antigens intracellularly and induced a higher level of cell-mediated immune (CMI) responses, as measured by IFN-gamma ELISPOT, intracellular cytokine staining (ICS), and cytotoxic T lymphocytes (CTL) assays against a dominant CD8(+) T cell epitope (AMQMLKETI). In contrast, the addition of a tissue plasminogen activator (tPA) leader sequence significantly improved overall Gag protein expression/secretion and Gag-specific antibody responses; however, Gag-specific CMI responses were decreased.

Cross-reactive human B cell and T cell epitopes between influenza A and B viruses.

Influenza A and B viruses form different genera, which were originally distinguished by antigenic differences in their nucleoproteins and matrix 1 proteins. Cross-protection between these two genera has not been observed in animal experiments, which is consistent with the low homology in viral proteins common to both viruses except for one of three polymerase proteins, polymerase basic 1 (PB1). Recently, however, antibody and CD4+ T cell epitopes conserved between the two genera were identified in humans.

CD4+ T cells provide intermolecular help to generate robust antibody responses in vaccinia virus-vaccinated humans.

Immunization with vaccinia virus elicits a protective Ab response that is almost completely CD4(+) T cell dependent. A recent study in a rodent model observed a deterministic linkage between Ab and CD4(+) T cell responses to particular vaccinia virus proteins suggesting that CD4(+) T cell help is preferentially provided to B cells with the same protein specificity (Sette et al. 2008.

Dengue viral RNA levels in peripheral blood mononuclear cells are associated with disease severity and preexisting dengue immune status.

Background: Infection with dengue viruses (DENV) causes a wide range of manifestations from asymptomatic infection to a febrile illness called dengue fever (DF), to dengue hemorrhagic fever (DHF). The in vivo targets of DENV and the relation between the viral burden in these cells and disease severity are not known.

Method: The levels of positive and negative strand viral RNA in peripheral blood monocytes, T/NK cells, and B cells and in plasma of DF and DHF cases were measured by quantitative RT-PCR.

Comparison of complement dependent lytic, hemagglutination inhibition and microneutralization antibody responses in influenza vaccinated individuals.

Virus specific, non-neutralizing antibodies such as complement dependent lytic (CDL) antibodies may reduce morbidity following infection through the clearance of infectious virus particles and infected cells. We examined hemagglutination inhibition (HAI), microneutralization (MN) and CDL antibody titers to influenza A H1 and H3 virus strains in 23 healthy young adults who received the 2005-2006 trivalent inactivated influenza vaccine. Post vaccination, we detected statistically significant increases in MN and CDL antibodies but not in HAI antibodies.

A human CD4+ T cell epitope in the influenza hemagglutinin is cross-reactive to influenza A virus subtypes and to influenza B virus.

The hemagglutinin protein (HA) of the influenza virus family is a major antigen for protective immunity. Thus, it is a relevant target for developing vaccines. Here, we describe a human CD4(+) T cell epitope in the influenza virus HA that lies in the fusion peptide of the HA.

The degree of leukocytosis and urine GATA-3 mRNA levels are risk factors for severe acute kidney injury in Puumala virus nephropathia epidemica.

Puumala hantavirus (PUUV) infection, also known as nephropathia epidemica, is the most common cause of hemorrhagic fever with renal syndrome (HFRS) in Europe. The pathogenesis of PUUV nephropathia epidemica is complex and multifactorial, and the risk factors for severe acute kidney injury (AKI) during acute PUUV infection are not well defined. We conducted a prospective study of hospitalized patients with PUUV infection in Tampere, Finland to identify acute illness risk factors for HFRS severity.

T-cell responses to dengue virus in humans.

Dengue virus (DENV) is a leading cause of morbidity and mortality in most tropical and subtropical areas of the world. Dengue virus infection induces specific CD4+CD8- and CD8+CD4- T cells in humans. In primary infection, T-cell responses to DENV are serotype cross-reactive, but the highest response is to the serotype that caused the infection.