Confocal laser scanning microscopy of the urinary bladder.

<p><i>In vivo</i> confocal laser scanning microscopy of the bladder showing eggs of <i>Schistosoma haematobium</i> (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034869#pone-0034869-g001" target="_blank">figure 1a and 1b</a>) with their typical terminal spine (arrow) (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034869#pone-0034869-g001" target="_blank">figure 1b</a>).</p

Data_Sheet_1_Host Defense Versus Immunosuppression: Unisexual Infection With Male or Female Schistosoma mansoni Differentially Impacts the Immune Response Against Invading Cercariae.docx

<p>Infection with the intravascular diecious trematode Schistosoma spp. remains a serious tropical disease and public health problem in the developing world, affecting over 258 million people worldwide. During chronic Schistosoma mansoni infection, complex immune responses to tissue-entrapped parasite eggs provoke granulomatous inflammation which leads to serious damage of the liver and intestine. The suppression of protective host immune mechanisms by helminths promotes parasite survival and benefits the host by reducing tissue damage. However, immune-suppressive cytokines may reduce vaccine-induced immune responses. By combining a single-sex infection system with a murine air pouch model, we were able to demonstrate that male and female schistosomes play opposing roles in modulating the host’s immune response. Female schistosomes suppress early innate immune responses to invading cercariae in the skin and upregulate anergy-associated genes. In contrast, male schistosomes trigger strong innate immune reactions which lead to a reduction in worm and egg burden in the liver. Our data suggest that the female worm is a neglected player in the dampening of the host’s immune defense system and is therefore a promising target for new immune modulatory therapies.</p

Clinical Trial to Evaluate the Safety and Immunogenicity of a Trivalent Surface Antigen Seasonal Influenza Vaccine Produced in Mammalian Cell Culture and Administered to Young and Elderly Adults with and without A(H1N1) Pre-Vaccination

<div><p></p><p>Vaccination against influenza is an important means of reducing morbidity and mortality in subjects at risk. The prevalent viral strains responsible for seasonal epidemics usually change annually, but the WHO recommendations for the 2011/2012-season in the Northern hemisphere included the same antigens as for the previous season.</p><p>We conducted a single-center, single-arm study involving 62 younger (18–60 years) and 64 older (>60 years) adults to test the immunogenicity, safety and tolerability of a trivalent surface antigen, inactivated influenza vaccine produced in mammalian cell-culture. The vaccine contained 15 µg hemagglutinin of each of the virus strains recommended for the 2011–2012 Northern hemisphere winter season (A/California/7/09 (H1N1)-; A/Perth/16/09 (H3N2)-; B/Brisbane/60/08-like strain) in a non-adjuvanted preservative-free formulation. Antibody response was measured by hemagglutination inhibition 21 days after immunization. Adverse events and safety were assessed using subject diary cards and telephone interviews.</p><p>Seroconversion or a 4-fold antibody increase in antibody titers was detectable against A(H1N1) in 68% of both younger and older adults, against A(H3N2) in 53% and 27%, and against the B influenza strain in 35% and 17%. Antibody titers of 40 or more were observed against A(H1N1) in 87% and 90% of younger and older adults, against A(H3N2) in 98% and 98%, and against the B influenza strain in 93% and 90%. Pre-vaccination antibody titers were protective against A(H1N1), A(H3N2) and B in 38%, 58% and 58%, respectively, of younger and in 43%, 88% and 70% of older adults. Among subjects with previous A(H1N1) vaccination only 48% of younger and 47% of older adults had protective A(H1N1) antibodies at inclusion. Adverse reactions were generally mild. The most frequently reported reactions were pain at the injection site, myalgia and fatigue.</p><p>The vaccine generated protective antibodies against all three viral strains and had an acceptable safety profile in both younger and older adults.</p><p>Trial Registration</p><p><a href="http://ClinicalTrials.gov" target="_blank">ClinicalTrials.gov</a><a href="http://clinicaltrials.gov/ct2/show/NCT01422512" target="_blank">NCT01422512</a></p></div

Evaluation of the antibody titers to pandemic A(H1N1) antigen prior to vaccination in the intention-to-treat analysis.

1<p>Vaccination containing pandemic A(H1N1) antigen: either 2009 pandemic A(H1N1) vaccine or the 2010/2011 northern hemisphere seasonal influenza vaccine.</p>2<p>pre-vaccination HI titer ≥40.</p

Vaccine immunogenicity assessed by HI assay - per protocol population.

1<p>n/N: responders (n) as proportion of the (sub-)population (N).</p>2<p>GMT: geometric mean titer;</p>3<p>95% CI: 95% confidence interval.</p>4<p>Seroprotection rate: proportion of subjects with a protective titer pre- or post-vaccination (titer ≥40).</p>5<p>Seroconversion rate: proportion of subjects with antibody increase from <10 pre-vaccination to ≥40 post-vaccination.</p>6<p>Significant increase: proportion of subjects with an antibody titer of ≥10 pre-vaccination and 4-fold antibody increase post-vaccination.</p>7<p>CHMP criteria.</p>8<p>GM increase = geometric mean increase.</p

Percentage of younger (<61 years of age) and older (≥61 years of age) subjects who experienced solicited local (A) or systemic (B) adverse events.

<p>None had severe adverse reactions.</p

Flowchart of the number of subjects included and analyzed.

<p>Flowchart of the number of subjects included and analyzed.</p

Licensing criteria for influenza vaccine immunogenicity laid down by the European Committee for Medicinal Products for Human Use.

1<p>Either a pre-vaccination HI titer<1∶10 and a post-vaccination HI titer ≥1∶40 or a pre-vaccination HI titer ≥1∶10 and a minimum four-fold rise in post-vaccination HI antibody titer.</p

Main inclusion and exclusion criteria for the study population.

<p>Main inclusion and exclusion criteria for the study population.</p

Mean daily treatment costs of antiretrovirals by class and year after adjustment for the German consumer price index (1996 = 100), annual increments of consumer price index in %: 1996: 1.4%, 1997: 1.9%; 1998: 1.0%; 1999: 0.6%; 2000: 1,4%; 2001: 1.9%; 2002: 1.5%; 2003: 1.0%; 2004: 1.7%; 2005: 1.5%; 2006: 1.6%; 2007: 2.3%; 2008: 2.6%.

<p>Mean daily treatment costs of antiretrovirals by class and year after adjustment for the German consumer price index (1996 = 100), annual increments of consumer price index in %: 1996: 1.4%, 1997: 1.9%; 1998: 1.0%; 1999: 0.6%; 2000: 1,4%; 2001: 1.9%; 2002: 1.5%; 2003: 1.0%; 2004: 1.7%; 2005: 1.5%; 2006: 1.6%; 2007: 2.3%; 2008: 2.6%.</p