795 research outputs found
Integration of vitamin A supplementation with the expanded program on immunization does not affect seroconversion to oral poliovirus vaccine in infants
Integration of vitamin A supplementation with the expanded program on immunization does not affect seroconversion to oral poliovirus vaccine in infants
Comparison of two enzyme-linked immunosorbent assays and one rapid immunoblot assay for detection of herpes simplex virus type 2-specific antibodies in serum
MVA-based H5N1 vaccine affords cross-clade protection in mice against influenza A/H5N1 viruses at low doses and after single immunization.
Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amount of vaccine preparations that can be produced is limited. Furthermore, protective immunity is induced ideally after a single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccine were assessed in mice. To this end, mice were vaccinated once or twice with descending doses of a recombinant MVA expressing the HA gene of influenza virus A/Vietnam/1194/04. The protective efficacy was determined after challenge infection with the homologous clade 1 virus and a heterologous virus derived from clade 2.1, A/Indonesia/5/05 by assessing weight loss, virus replication and histopathological changes. It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate
Linking Influenza Virus Tissue Tropism to Population-Level Reproductive Fitness
Influenza virus tissue tropism defines the host cells and tissues that support viral replication and contributes to determining which regions of the respiratory tract are infected in humans. The location of influenza virus infection along the respiratory tract is a key determinant of virus pathogenicity and transmissibility, which are at the basis of influenza burdens in the human population. As the pathogenicity and transmissibility of influenza virus ultimately determine its reproductive fitness at the population level, strong selective pressures will shape influenza virus tissue tropisms that maximize fitness. At present, the relationships between influenza virus tissue tropism within hosts and reproductive fitness at the population level are poorly understood. The selective pressures and constraints that shape tissue tropism and thereby influence the location of influenza virus infection along the respiratory tract are not well characterized. We use mathematical models that link within-host infection dynamics in a spatially-structured human respiratory tract to between-host transmission dynamics, with the aim of characterizing the possible selective pressures on influenza virus tissue tropism. The results indicate that spatial heterogeneities in virus clearance, virus pathogenicity or both, resulting from the unique structure of the respiratory tract, may drive optimal receptor binding affinity-that maximizes influenza virus reproductive fitness at the population level-towards sialic acids with α2,6 linkage to galactose. The expanding cell pool deeper down the respiratory tract, in association with lower clearance rates, may result in optimal infectivity rates-that likewise maximize influenza virus reproductive fitness at the population level-to exhibit a decreasing trend towards deeper regions of the respiratory tract. Lastly, pre-existing immunity may drive influenza virus tissue tropism towards upper regions of the respiratory tract. The propo
Contaminant-related suppression of delayed-type hypersensitivity and antibody responses in harbor seals fed herring from the Baltic Sea.
Recent mass mortalities among several marine mammal populations have led to speculation about increased susceptibility to viral infections as a result of contaminant-induced immunosuppression. In a 2.5-year study, we fed herring from either the relatively uncontaminated Atlantic Ocean or the contaminated Baltic Sea to two groups of captive harbor seals and monitored immune function in the seals. Seals fed the contaminated fish were less able to mount a specific immunological response to ovalbumin, as measured by in vivo delayed-type hypersensitivity (DTH) reactions and antibody responses. The skin reaction to this protein antigen was characterized by the appearance of mononuclear cells which peaked at 24 hr after intradermal administration, characteristic of DTH reactions in other animals studied. These DTH responses correlated well with in vitro tests of T-lymphocyte function, implicating this cell type in the reaction. Aryl-hydrocarbon (Ah) receptor-dependent toxic equivalent (TEQ) profiles in blubber biopsies taken from the seals implicated polychlorinated biphenyls rather than dioxins or furans in the observed immunosuppression. Marine mammal populations currently inhabiting polluted coastal environments in Europe and North America may therefore have an increased susceptibility to infections, and pollution may have played a role in recent virus-induced mass mortalities
Dolphin morbillivirus infection in different parts of the Mediterranean Sea
Morbillivirus were isolated from Mediterranean striped dolphins (Stenella coeruleoalba) dying along the coasts of Italy and Greece in 1991. They were antigenically identical to the morbilliviruses isolated from striped dolphins in Spain in 1990
High seroprevalence of human herpesviruses in HIV-infected individuals attending primary healthcare facilities in rural South Africa
Seroprevalence data of human herpesviruses (HHVs) are limited for sub-Saharan Africa. These are important to provide an indication of potential burden of HHV-related disease, in particular in human immunodeficiency virus (HIV)-infected individuals who are known to be at increased risk of these conditions in the Western world. In this cross-sectional study among 405 HIV-infected and antiretroviral therapy naïve individuals in rural South Africa the seroprevalence of HHVs was: herpes simplex virus type 1 (HSV-1) (98%), herpes simplex virus type 2 (HSV-2) (87%), varicella zoster virus (VZV) (89%), and 100% for both Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Independent factors associated with VZV seropositivity were low educational status and having children. Lack of in-house access to drinking water was independently associated with positive HSV-1 serostatus, whereas Shangaan ethnicity was associated with HSV-2 seropositivity. Increasing age was associated with higher IgG titres to both EBV and CMV, whereas CD4 cell count was negatively associated with EBV and CMV IgG titres. Moreover, IgG titres of HSV-1 and 2, VZV and CMV, and CMV and EBV were positively correlated. The high HHV seroprevalence emphasises the importance of awareness of these viral infections in HIV-infected individuals in South Africa
Zanamivir susceptibility monitoring and characterization of influenza virus clinical isolates obtained during phase II clinical efficacy studies
Zanamivir is a highly selective neuraminidase (NA) inhibitor with
demonstrated clinical efficacy against influenza A and B virus infections.
In phase II clinical efficacy trials (NAIB2005 and NAIB2008), virological
substudies showed mean reductions in virus shedding after 24 h of
treatment of 1.5 to 2.0 log(10) 50% tissue culture infective doses
compared to a placebo, with no reemergence of virus after the completion
of therapy. Paired isolates (n = 41) obtained before and during therapy
with zanamivir demonstrated no shifts in susceptibility to zanamivir when
measured by NA assays, although for a few isolates NA activity was too low
to evaluate. In plaque reduction assays in MDCK cells, the susceptibility
of isolates to zanamivir was extremely variable even at baseline and did
not correlate with the speed of resolution of virus shedding. Isolates
with apparent limited susceptibility to zanamivir by plaque reduction
proved highly susceptible in vivo in the ferret model. Further sequence
analysis of paired isolates revealed no changes in the hemagglutinin and
NA genes in the majority of isolates. The few changes observed were all
natural variants. No amino acid changes that had previously been
identified in vitro as being involved with reduced susceptibility to
zanamivir were observed. These studies highlighted problems associated
with monitoring susceptibility to NA inhibitors in the clinic, in that no
reliable cell-based assay is available. At present the NA assay is the
best available predictor of susceptibility to NA inhibitors in vivo, as
measured in the validated ferret model of infection
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