Maternal transfer of anti HPV 6 and 11 antibodies upon immunization with the 9-valent HPV vaccine.

BACKGROUND: This exploratory analysis was conducted to characterize the level of HPV types 6/11 antibodies in peripartum maternal blood and in cord blood of infants born to women who received 9-valent HPV (9vHPV) vaccine or quadrivalent HPV (qHPV) vaccine in a pivotal efficacy study (V503-001, NCT 00543543). METHODS: A total of 21 mother-infant pairs had evaluable HPV 6/11 results available for analysis. HPV6/11 antibodies were assessed using competitive Luminex immunoassay. The distribution of the ratios of infant to mother anti-HPV antibodies (i.e., infant-anti-HPV/mother- anti-HPV) was summarized. RESULTS: All mothers and infants were seropositive to HPV 6 and HPV 11. Anti-HPV 6/11 geometric mean titers (GMTs) in peripartum maternal blood and in cord blood of infant born to study participants were highly correlated. A 100% of infants born to seropositive mothers were also seropositive. The GMT ratios of peripartum maternal blood vs. those in cord blood were HPV 6: 1.23 [0.43, 3.49] and HPV 11: 1.29 [0.54, 3.07] in the 9vHPV vaccine group and HPV 6: 1.33 [0.41, 4.29] and HPV 11: 1.19 [0.45, 3.13] in the qHPV vaccine group, respectively. CONCLUSIONS: These results indicate that antibodies induced by the 9vHPV vaccine cross the placenta, which could potentially be beneficial against HPV6/11 infection and related disease such as recurrent respiratory papillomatosis.

Coarse corn particles cause a negative effect on eggshell quality of semi-heavy laying hens.

One of the possible ways to optimize the productive performance of poultry is through the physical processing of ingredients, which can improve the use of nutrients in these animals. In this context, this study was to evaluate the effects of different corn particle sizes in diets on the productive performance and egg quality of semi-heavy laying hens. Sixty naked neck laying hens were used from 24 weeks of age and distributed in a completely randomized design. Experimental diets in different treatments contained corn grain ground into sieves with a diameter of 2, 4, or 8 mm to provide corn particles with a geometric mean diameter (GMD) of 605 (fine), 1,030 (medium), and 2,280 µm (coarse), respectively. The feed and leftovers were weighed daily throughout the experimental period to determine the feed intake and feed conversion. Different corn particle sizes did not affect any aspect of the productive performance of hens, except for feed intake. Hens fed fine and medium corn particles exhibited higher values for egg yolk color, eggshell weight, and eggshell thickness. It is suggested that semi-heavy laying hens should be fed mash diets containing corn particles with GMD from 605 to 1,030 µm, because coarse corn particles cause a negative effect on eggshell quality.

Evaluation of a new syringe presentation of reduced-antigen content diphtheria, tetanus, and acellular pertussis vaccine in healthy adolescents--A single blind randomized trial.

Reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) vaccine, Boostrix™, is indicated for booster vaccination of children, adolescents and adults. The original prefilled disposable dTpa syringe presentation was recently replaced by another prefilled-syringe presentation with latex-free tip-caps and plunger-stoppers. 671 healthy adolescents aged 10-15 years who had previously received 5 or 6 previous DT(P)/dT(pa) vaccine doses, were randomized (1:1) to receive dTpa booster, injected using the new (dTpa-new) or previous syringe (dTpa-previous) presentations. Immunogenicity was assessed before and 1-month post-booster vaccination; safety/reactogenicity were assessed during 31-days post-vaccination. Non-inferiority of dTpa-new versus dTpa-previous was demonstrated for all antigens (ULs 95% CIs for GMC ratios ranged between 1.03-1.13). 1-month post-booster, immune responses were in similar ranges for all antigens with both syringe presentations. dTpa delivered using either syringe presentation was well-tolerated. These clinical results complement the technical data and support the use of the new syringe presentation to deliver the dTpa vaccine.

A correlation of measles specific antibodies and the number of plasmacytoid dendritic cells is observed after measles vaccination in 9 month old infants.

Measles virus (MeV) represents one of the main causes of death among young children, particularly in developing countries. Upon infection, MeV controls both interferon induction (IFN) and the interferon signaling pathway which results in a severe host immunosuppression that can persists for up to 6 mo after infection. Despite the global biology of MeV infection is well studied, the role of the plasmacytoid dendritic cells (pDCs) during the host innate immune response after measles vaccination remains largely uncharacterized. Here we investigated the role of pDCs, the major producers of interferon in response to viral infections, in the development of adaptive immune response against MeV vaccine. We report that there is a strong correlation between pDCs population and the humoral immune response to Edmonston Zagreb (EZ) measles vaccination in 9-month-old mexican infants. Five infants were further evaluated after vaccination, showing a clear increase in pDCs at baseline, one week and 3 months after immunization. Three months postvaccination they showed increase in memory T-cells and pDCs populations, high induction of adaptive immunity and also observed a correlation between pDCs number and the humoral immune response. These findings suggest that the development and magnitude of the adaptive immune response following measles immunization is directly dependent on the number of pDCs of the innate immune response.

Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents.

This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with ≥68% of subjects achieving hSBA titers ≥5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever (≥38.0°C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885].

Assessment of bivalent and tetravalent dengue vaccine formulations in flavivirus-naïve adults in Mexico.

UNLABELLED: Several ChimeriVax-Dengue (CYD)-based vaccination strategies were investigated as potential alternatives to vaccination with tetravalent CYD vaccine (CYD-TDV) in this phase IIa trial conducted in 2008-9 in 150 healthy adults. Participants were randomized and vaccinated on D0 and D105 (± 15 days). One group received bivalent CYD vaccine against serotypes 1 and 3 (CYD-1;3) on day 0 and CYD-2;4 on day 105 (± 15 days). Two groups received an injection at each timepoint of a tetravalent blend of CYD-1;3;4 and a VERO cell derived, live attenuated vaccine against serotype 2 (VDV-2), or the reference CYD-TDV. A fourth group received Japanese encephalitis (JE) vaccine on days -14, -7 and 0, followed by CYD-TDV on day 105. Viraemia was infrequent in all groups. CYD-4 viraemia was most frequent after tetravalent vaccination, while CYD-3 viraemia was most frequent after the first bivalent vaccination. Immunogenicity as assessed by 50% plaque reduction neutralisation test on D28 was comparable after the first injection of either tetravalent vaccine, and increased after the second injection, particularly with the blended CYD-1;3;4/ VDV-2 vaccine. In the bivalent vaccine group, immune response against serotype 3 was highest and the second injection elicited a low immune response against CYD 2 and 4. Immune responses after the first injection of CYD-TDV in the JE-primed group were in general higher than after the first injection in the other groups. All tested regimens were well tolerated without marked differences between groups. Bivalent vaccination showed no advantage in terms of immunogenicity. CLINICAL TRIAL REGISTRATION NUMBER: NCT00740155.

Experimental evolution of bet hedging under manipulated environmental uncertainty in Neurospora crassa.

All organisms are faced with environmental uncertainty. Bet-hedging theory expects unpredictable selection to result in the evolution of traits that maximize the geometric-mean fitness even though such traits appear to be detrimental over the shorter term. Despite the centrality of fitness measures to evolutionary analysis, no direct test of the geometric-mean fitness principle exists. Here, we directly distinguish between predictions of competing fitness maximization principles by testing Cohen's 1966 classic bet-hedging model using the fungus Neurospora crassa. The simple prediction is that propagule dormancy will evolve in proportion to the frequency of 'bad' years, whereas the prediction of the alternative arithmetic-mean principle is the evolution of zero dormancy as long as the expectation of a bad year is less than 0.5. Ascospore dormancy fraction in N. crassa was allowed to evolve under five experimental selection regimes that differed in the frequency of unpredictable 'bad years'. Results were consistent with bet-hedging theory: final dormancy fraction in 12 genetic lineages across 88 independently evolving samples was proportional to the frequency of bad years, and evolved both upwards and downwards as predicted from a range of starting dormancy fractions. These findings suggest that selection results in adaptation to variable rather than to expected environments.

Regulatory and effector T-cells are differentially modulated by Dexamethasone.

It is assumed that the ratio between effector T cells (Teff) and regulatory T cells (Tregs) controls the immune reactivity within the T-cell compartment. The purpose of this study was to investigate if Dexamethasone (Dex) affects Teff and Tregs subsets. Dex induced on Tregs a dose and time-dependent apoptosis which resulted in a relative increase of Teff. After TCR activation, Dex induced a strong proliferative inhibition of Teff, but a weaker proliferative inhibition on Tregs. These effects were modulated by IL-2, which not only restored the proliferative response, but also prevented Dex-induced apoptosis. The highest dose of IL-2 prevented apoptosis on all FOXP3+CD4+ T cells. Meanwhile, the lowest dose only rescued activated Tregs (aTregs), probably related to their CD25 higher expression. Because Dex did not affect the suppressor capacity of aTregs either, our results support the notion that under Dex treatment, the regulatory T-cell compartment maintains its homeostasis.

Predictors of urinary bisphenol A and phthalate metabolite concentrations in Mexican children.

Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) and phthalates is prevalent among children and adolescents, but little is known regarding important sources of exposure at these sensitive life stages. In this study, we measured urinary concentrations of BPA and nine phthalate metabolites in 108 Mexican children aged 8-13 years. Associations of age, time of day, and questionnaire items on external environment, water use, and food container use with specific gravity-corrected urinary concentrations were assessed, as were questionnaire items concerning the use of 17 personal care products in the past 48-h. As a secondary aim, third trimester urinary concentrations were measured in 99 mothers of these children, and the relationship between specific gravity-corrected urinary concentrations at these two time points was explored. After adjusting for potential confounding by other personal care product use in the past 48-h, there were statistically significant (p<0.05) positive associations in boys for cologne/perfume use and monoethyl phthalate (MEP), mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), and in girls for colored cosmetics use and mono-n-butyl phthalate (MBP), mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP, and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), conditioner use and MEP, deodorant use and MEP, and other hair products use and MBP. There was a statistically significant positive trend for the number of personal care products used in the past 48-h and log-MEP in girls. However, there were no statistically significant associations between the analytes and the other questionnaire items and there were no strong correlations between the analytes measured during the third trimester and at 8-13 years of age. We demonstrated that personal care product use is associated with exposure to multiple phthalates in children. Due to rapid development, children may be susceptible to impacts from exposure to endocrine disrupting chemicals; thus, reduced or delayed use of certain personal care products among children may be warranted.

Determinants of urinary bisphenol A concentrations in Mexican/Mexican--American pregnant women.

Prenatal exposure to bisphenol A (BPA) may be associated with adverse health effects in the developing fetus; however, little is known about predictors of BPA exposure during pregnancy. We examined BPA exposure in 491 pregnant women from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) cohort and explored the role of living in the United States on significant dietary predictors of BPA exposure. Women provided urine samples up to two times during pregnancy (n=866 total samples). We computed the intraclass correlation coefficient (ICC) to evaluate variability in concentrations between collections and used generalized estimating equation (GEE) models to assess predictors of exposure. Geometric mean (GSD) BPA concentrations were 0.9 (2.8)µg/L and 1.0 (2.6)µg/L at the first and second prenatal visits, respectively. We observed greater within- than between-woman variability in urinary BPA concentrations (ICC=0.22). GEE models suggest that women who lived in the United States their entire life had 38% (CI: -0.1, 89.3) higher urinary BPA concentrations compared with other immigrant women. Additionally, women who consumed ≥3 sodas per day or hamburgers three times a week or more had 58% (CI: 18.0, 112.1) and 20% (CI: -0.2, 45.2) higher urinary BPA concentrations, respectively, compared with women who consumed no sodas or hamburgers. A higher percentage of women who lived their entire life in the United States reported increased consumption of sodas and hamburgers compared with other immigrant women. Independent of other factors, BPA urinary concentrations were slightly higher when the sample was collected later in the day. As in previous studies, high within-woman variability in urinary BPA concentrations confirms that several samples are needed to properly characterize exposure during pregnancy. Results also suggest that some factors could be modified to minimize exposures during pregnancy in our study participants (e.g., reducing soda and hamburger intake) and that factors associated with acculturation might increase BPA concentrations.

Effects of corn particle size and physical form of the diet on the gastrointestinal structures of broiler chickens

The objective of this experiment was to investigate the effects of different particle sizes, expressed as Geometric Mean Diameter (GMD) of corn (0.336mm, 0.585mm, 0.856mm and 1.12mm) of mash and pelleted broiler chicken diets on the weight of the gizzard, duodenum and jejunum+ileum; on the pH of the gizzard and small intestine and on the characteristics of the duodenal mucous layer (number and height of villi and crypt depth) in 42-day-old broilers. The physical form and the particle size of the diet had no significant effect on gizzard and intestine pH (p > 0.05). A greater gizzard weight was seen in the birds receiving pelleted diet and particle size of 0.336mm (p 0.008). However, for the particle sizes of 0.856 and 1.12 mm, a greater weight was found in birds that received mash diet (p 0.039 and p 0.006, respectively). Also, gizzard weight was greater with increasing corn GMD independent of the physical form of the diet. In the mash diet, the increase in particle size promoted a quadratic response in the weight of duodenum and jejunum + ileum. The pelleted diet promoted a greater number of villi per transverse duodenum cut (p 0.007) and greater crypt depth (p 0.05). As the particle size increased, there was a linear increase of villus height and crypt depth in the duodenum, irrespective of the physical form of the diet.

Effects of corn particle size and physical form of the diet on the gastrointestinal structures of broiler chickens

The objective of this experiment was to investigate the effects of different particle sizes, expressed as Geometric Mean Diameter (GMD) of corn (0.336mm, 0.585mm, 0.856mm and 1.12mm) of mash and pelleted broiler chicken diets on the weight of the gizzard, duodenum and jejunum+ileum; on the pH of the gizzard and small intestine and on the characteristics of the duodenal mucous layer (number and height of villi and crypt depth) in 42-day-old broilers. The physical form and the particle size of the diet had no significant effect on gizzard and intestine pH (p > 0.05). A greater gizzard weight was seen in the birds receiving pelleted diet and particle size of 0.336mm (p 0.008). However, for the particle sizes of 0.856 and 1.12 mm, a greater weight was found in birds that received mash diet (p 0.039 and p 0.006, respectively). Also, gizzard weight was greater with increasing corn GMD independent of the physical form of the diet. In the mash diet, the increase in particle size promoted a quadratic response in the weight of duodenum and jejunum + ileum. The pelleted diet promoted a greater number of villi per transverse duodenum cut (p 0.007) and greater crypt depth (p 0.05). As the particle size increased, there was a linear increase of villus height and crypt depth in the duodenum, irrespective of the physical form of the diet.

Tamanho da Partícula do Milho e Forma Física da Ração e Seus Efeitos Sobre o Desempenho e Rendimento de Carcaça de Frangos de Corte

The experiment was conducted to evaluate the effect of different corn particle size, expressed as geometric mean diameter (GMD)(0.336 mm, 0.585mm, 0.856 mm and 1.12 mm) and two diet forms (mash-M and pellets-P) on performance and carcass yield of broilers from 21 to 42 days of age. M diets, produced with 0.336 mm of GMD resulted in lower feed intake (FI) (p 0.001), lower weight gain (WG) (p 0.001) and worse feed efficiency (FE) (p 0.001) than 0.336 mm P diets. M and P diets with other GMD did not show differences in performance. When particle size was evaluated itself, increments in GMD resulted a linear increase on WG and a quadratic increase on FI and FE. Neither form of diet nor particle size influenced carcass and leg+drumstick yields, although breast yield decreased with M diet,0.336 mm GMD (p 0.001).

Este experimento foi realizado com o objetivo de investigar os efeitos de diferentes granulometrias, expressa em Diâmetro Geométrico Médio (DGM) do milho (0,336mm, 0,585mm, 0,856 mm e 1,12 mm) de dietas fornecidas na forma farelada (FAR) e peletizada (PEL), no desempenho e no rendimento de carcaça e de cortes de frangos de corte de 21 a 42 dias de idade. Dietas FAR, produzidas com DGM de 0,336 mm resultaram em um menor consumo (p 0,001), ganho de peso (p 0,001) e pior conversão alimentar (p 0,001) do que as PEL de mesmo DGM. Os demais DGM não mostraram diferenças entre ração FAR e PEL. Quando avaliada somente a granulometria, observou-se que o aumento no DGM melhorou o ganho de peso linearmente e de forma quadrática o consumo e a conversão alimentar. Não houve influência da forma física ou DGM em rendimento de carcaça e rendimento de perna+coxa. Porém foi verificada uma redução em rendimento de peito com DGM 0,336 mm (p 0,001), na forma FAR.

Tamanho da Partícula do Milho e Forma Física da Ração e Seus Efeitos Sobre o Desempenho e Rendimento de Carcaça de Frangos de Corte

The experiment was conducted to evaluate the effect of different corn particle size, expressed as geometric mean diameter (GMD)(0.336 mm, 0.585mm, 0.856 mm and 1.12 mm) and two diet forms (mash-M and pellets-P) on performance and carcass yield of broilers from 21 to 42 days of age. M diets, produced with 0.336 mm of GMD resulted in lower feed intake (FI) (p 0.001), lower weight gain (WG) (p 0.001) and worse feed efficiency (FE) (p 0.001) than 0.336 mm P diets. M and P diets with other GMD did not show differences in performance. When particle size was evaluated itself, increments in GMD resulted a linear increase on WG and a quadratic increase on FI and FE. Neither form of diet nor particle size influenced carcass and leg+drumstick yields, although breast yield decreased with M diet,0.336 mm GMD (p 0.001).

Este experimento foi realizado com o objetivo de investigar os efeitos de diferentes granulometrias, expressa em Diâmetro Geométrico Médio (DGM) do milho (0,336mm, 0,585mm, 0,856 mm e 1,12 mm) de dietas fornecidas na forma farelada (FAR) e peletizada (PEL), no desempenho e no rendimento de carcaça e de cortes de frangos de corte de 21 a 42 dias de idade. Dietas FAR, produzidas com DGM de 0,336 mm resultaram em um menor consumo (p 0,001), ganho de peso (p 0,001) e pior conversão alimentar (p 0,001) do que as PEL de mesmo DGM. Os demais DGM não mostraram diferenças entre ração FAR e PEL. Quando avaliada somente a granulometria, observou-se que o aumento no DGM melhorou o ganho de peso linearmente e de forma quadrática o consumo e a conversão alimentar. Não houve influência da forma física ou DGM em rendimento de carcaça e rendimento de perna+coxa. Porém foi verificada uma redução em rendimento de peito com DGM 0,336 mm (p 0,001), na forma FAR.

Evaluation of Leishmania antigens preparation and storage for use in enzyme immunoassays

The influence of time and temperature on the storage of an alkaline antigen of L. major-like and L.(V.) braziliensis promastigotes added or not of a proteases inhibitor (PMSF) was evaluated by means of an IgG-ELISA. Antibodies in assays using L. major-like antigen stored at -20 degrees C for 6 months had a statistically lower geometric mean titer (GMT) and different 95% confidence interval limits (CL) than antigens stored otherwise, as assessed by the [quot ]t[quot ] statistic. The PMSFL. major-like antigen after storage for 6 months at a temperature of 4 degrees C had the same GMT and 95% CL displayed at time zero as well as when storage for 4 and 6 months at -20 degrees C. Significant differences were not found when L.(V.) braziliensis antigens were stored at times and temperatures mentioned; the PMSF antigen stored for 2 months at -70 degrees C resulted in a lower serum GMT and 95% CL than any other, as assessed by the [quot ]t[quot ] statistic. Antigen performance did not show any statistical difference associated to the addition of PMSF within the same species; the largest difference between antigens was that between PMSF-L. (V.) braziliensis and L. major-like without PMSF.

A influência do tempo e temperatura de estocagem de antígenos alcalinos de promastigotas de L. major-like e L. (V.) braziliensis adicionados ou não de um inibidor de proteases foi avaliada por meio de reações de IgG-ELISA. A reação que empregava o antígeno de L. major-like estocado por 6 meses a -20oC mostrou que médias geométricas dos títulos (MGT)e intervalos de confiança 95% (IC 95%) eram estatisticamente inferiores àquelas obtidas com antígenos estocados em outros intervalos de tempo, medido pela estatística "t". O antígeno PMSF-L. major-like depois de 6 meses de estocagem à temperatura de 4oC tinha a mesma MGT e IC 95% do tempo zero assim como quando ele foi estocado a -20oC por 4 e 6 meses. Não foram observadas diferenças estatisticamente diferentes com os antígenos de L. (V.) braziliensis estocados nas mesmas condições de tempo e temperatura exceto o antígeno PMSF estocado por 2 meses a -70oC que apresentou MGT e IC 95% inferiores a quaisquer outras como aferido pela estatísitca "t". Quando comparados os desempenhos dos antígenos não houve direrenças estatisticamente significantes entre a adição ou não de PMSF para qualquer dos parasitas. A análise do cruzamento entre antígenos mostrou que a maior diferença netre eles foi a do contraste entre L. (V.) braziliensis adicionado de PMSF e L. major-like sem adição de PMSF.