The type of adjuvant in whole inactivated influenza a virus vaccines impacts vaccine-associated enhanced respiratory disease

Influenza A virus (IAV) causes a disease burden in the swine industry in the US and is a challenge to prevent due to substantial genetic and antigenic diversity of IAV that circulate in pig populations. Whole inactivated virus (WIV) vaccines formulated with oil-in-water (OW) adjuvant are commonly used in swine. However, WIV-OW are associated with vaccine-associated enhanced respiratory disease (VAERD) when the hemagglutinin and neuraminidase of the vaccine strain are mismatched with the challenge virus. Here, we assessed if different types of adjuvant in WIV vaccine formulations impacted VAERD outcome. WIV vaccines with a swine δ1-H1N2 were formulated with different commercial adjuvants: OW1, OW2, nano-emulsion squalene-based (NE) and gel polymer (GP). Pigs were vaccinated twice by the intramuscular route, 3 weeks apart, then challenged with an H1N1pdm09 three weeks post-boost and necropsied at 5 days post infection. All WIV vaccines elicited antibodies detected using the hemagglutination inhibition (HI) assay against the homologous vaccine virus, but not against the heterologous challenge virus; in contrast, all vaccinated groups had cross-reactive IgG antibody and IFN-γ responses against H1N1pdm09, with a higher magnitude observed in OW groups. Both OW groups demonstrated robust homologous HI titers and cross-reactivity against heterologous H1 viruses in the same genetic lineage. However, both OW groups had severe immunopathology consistent with VAERD after challenge when compared to NE, GP, and non-vaccinated challenge controls. None of the WIV formulations protected pigs from heterologous virus replication in the lungs or nasal cavity. Thus, although the type of adjuvant in the WIV formulation played a significant role in the magnitude of immune response to homologous and antigenically similar H1, none tested here increased the breadth of protection against the antigenically-distinct challenge virus, and some impacted immunopathology after challenge

Simultaneous Papillary Carcinoma in Thyroglossal Duct Cyst and Thyroid

Thyroglossal duct cyst (TDC) is a cystic expansion of a remnant of the thyroglossal duct tract. Carcinomas in the TDC are extremely rare and are usually an incidental finding after the Sistrunk procedure. In this report, an unusual case of a 36-year-old woman with concurrent papillary thyroid carcinoma arising in the TDC and on the thyroid gland is presented, followed by a discussion of the controversies surrounding the possible origins of a papillary carcinoma in the TDC, as well as the current management options

Molecular Characterization of the Schistosoma mansoni Zinc Finger Protein SmZF1 as a Transcription Factor

Schistosomes are parasites that exhibit a complex life cycle during which they progress through many morphological and physiological transformations. These transformations are likely accompanied by alterations in gene expression, making genetic regulation important for parasite development. Here we describe a Schistosoma mansoni protein (SmZF1) that may act as a parasite transcription factor. These factors are key proteins for gene regulation. We have previously demonstrated that SmZF1 is able to bind DNA and that its mRNA is present at different stages during the parasite life cycle. In this study we aimed to define if this protein can function as a transcription factor in S. mansoni. SmZF1 was detected in the nucleus of adult male worms, cercariae and schistosomula cells. It was not, however, observed in female cells, suggesting it to be gender specific. We used mammalian cells expressing recombinant SmZF1 to analyze if SmZF1 protein is able to activate/repress gene transcription and demonstrated that it increased the expression of a reporter gene by two-fold. The results obtained confirm SmZF1 as a S. mansoni transcription factor

O risco das falsas controvérsias científicas para as políticas ambientais brasileiras

Fake controversies have influenced policy making on health and environmental issues for decades, resulting in major implementation setbacks worldwide. As a case study, in this paper we examine fake controversies produced by a small group of active Brazilian researchers that have seriously impacted environmental conservation, particularly in issues related to deforestation and climate change. Based on the literature, we develop a typology of strategies deployed in fake controversies, which include manufacturing uncertainty, misusing scientific credentials, and disregarding scientific literature. Afterwards, we examine the influence of this group of contrarians at the National Congress. We then analyze the fake controversies promoted by these contrarians and argue that, to properly understand them, we need to consider a strategy so far overlooked in the literature: the manufacture of “pseudo-facts”, namely, affirmations at odds with the established literature but that strives to appear as scientific facts. Unlike other contexts, in which contrarians have mainly sought to cast doubt on consensual issues by arguing that there are still considerable uncertainties surrounding them, in Brazil pseudo-facts on deforestation have been produced and published outside the peer-reviewed literature. We conclude the study with recommendations on how to oppose fake scientific controversies that threaten environmental conservation in general.Falsas controvérsias têm influenciado a elaboração de políticas sobre questões ambientais e de saúde há décadas, resultando em grandes retrocessos na implementação dessas políticas em todo o mundo. Utilizando um estudo de caso, neste artigo são examinadas falsas controvérsias produzidas por um pequeno grupo de pesquisadores brasileiros que têm afetado seriamente a conservação ambiental, particularmente em questões relacionadas ao desmatamento e às mudanças climáticas. Com base na literatura, foi desenvolvida uma tipologia das estratégias empregadas em falsas controvérsias, que incluem a fabricação de incertezas, o uso indevido de credenciais científicas e a desconsideração da literatura científica. Posteriormente, foi examinada a influência desse grupo de negacionistas no Congresso Nacional. Analisam-se, então, as falsas controvérsias promovidas por esses negacionistas e argumenta-se que, para entendê-las adequadamente, é necessário considerar uma estratégia até agora negligenciada na literatura: a criação de “pseudofatos”, ou seja, afirmações em desacordo com a literatura científica já estabelecida, mas que são mascaradas para parecerem fatos científicos. Ao contrário de outros contextos, nos quais os negacionistas têm procurado principalmente lançar dúvidas sobre questões já consensuais, argumentando que ainda existem incertezas consideráveis em torno delas, no Brasil foram produzidos e publicados pseudofatos sobre o desmatamento fora do âmbito da literatura revisada por pares. Concluímos o estudo com recomendações sobre como se opor às falsas controvérsias científicas que ameaçam a conservação ambiental em geral

Beyond carbon: The contributions of South American tropical humid and subhumid forests to ecosystem services

Tropical forests are recognized for their role in providing diverse ecosystem services (ESs), with carbon uptake the best recognized. The capacity of tropical forests to provide ESs is strongly linked to their enormous biodiversity. However, causal relationships between biodiversity and ESs are poorly understood. This may be because biodiversity is often translated into species richness. Here we argue that focusing on multiple attributes of biodiversity—structure, composition, and function—will make relationships between biodiversity and ESs clearer. In this review, we discuss the ecological processes behind ESs from tropical humid and subhumid forests of South America. Our main goal is to understand the links between the ESs and those three biodiversity attributes. While supporting and regulating services relate more closely to forest structure and function, provisioning services relate more closely to forest composition and function, and cultural services are more related to structure and composition attributes. In this sense, ESs from subhumid forests (savannas) differ from those provided by the Amazon Forest, although both ecosystems are recognized as harboring tremendous biodiversity. Given this, if anthropogenic drivers of change promote a shift in the Amazon Forest toward savanna—the savannization hypothesis—the types of services provided will change, especially climate regulating services. This review emphasizes the importance of deeply understanding ecosystem structure, composition, and function to better understand the services ecosystems provide. Understanding that anthropogenic impacts on biodiversity occur through these three main attributes, it becomes easier to anticipate how humans will impact ESs

Plasticity of Amino Acid Residue 145 Near the Receptor Binding Site of H3 Swine Influenza A Viruses and Its Impact on Receptor Binding and Antibody Recognition.

The hemagglutinin (HA), a glycoprotein on the surface of influenza A virus (IAV), initiates the virus life cycle by binding to terminal sialic acid (SA) residues on host cells. The HA gradually accumulates amino acid substitutions that allow IAV to escape immunity through a mechanism known as antigenic drift. We recently confirmed that a small set of amino acid residues are largely responsible for driving antigenic drift in swine-origin H3 IAV. All identified residues are located adjacent to the HA receptor binding site (RBS), suggesting that substitutions associated with antigenic drift may also influence receptor binding. Among those substitutions, residue 145 was shown to be a major determinant of antigenic evolution. To determine whether there are functional constraints to substitutions near the RBS and their impact on receptor binding and antigenic properties, we carried out site-directed mutagenesis experiments at the single-amino-acid level. We generated a panel of viruses carrying substitutions at residue 145 representing all 20 amino acids. Despite limited amino acid usage in nature, most substitutions at residue 145 were well tolerated without having a major impact on virus replication in vitro All substitution mutants retained receptor binding specificity, but the substitutions frequently led to decreased receptor binding. Glycan microarray analysis showed that substitutions at residue 145 modulate binding to a broad range of glycans. Furthermore, antigenic characterization identified specific substitutions at residue 145 that altered antibody recognition. This work provides a better understanding of the functional effects of amino acid substitutions near the RBS and the interplay between receptor binding and antigenic drift.IMPORTANCE The complex and continuous antigenic evolution of IAVs remains a major hurdle for vaccine selection and effective vaccination. On the hemagglutinin (HA) of the H3N2 IAVs, the amino acid substitution N 145 K causes significant antigenic changes. We show that amino acid 145 displays remarkable amino acid plasticity in vitro, tolerating multiple amino acid substitutions, many of which have not yet been observed in nature. Mutant viruses carrying substitutions at residue 145 showed no major impairment in virus replication in the presence of lower receptor binding avidity. However, their antigenic characterization confirmed the impact of the 145 K substitution in antibody immunodominance. We provide a better understanding of the functional effects of amino acid substitutions implicated in antigenic drift and its consequences for receptor binding and antigenicity. The mutation analyses presented in this report represent a significant data set to aid and test the ability of computational approaches to predict binding of glycans and in antigenic cartography analyses

Genetic characterization of influenza virus circulating in Brazilian pigs during

Background Influenza A viruses circulating in pigs in Brazil are still not characterized, and only limited data are available about swine influenza epidemiology in the country. Therefore, we characterized the hemagglutinin (HA) and neuraminidase (NA) genes of influenza viruses isolated from Brazilian pigs. We also evaluated one case of probable swine-to-human transmission. Methods Twenty influenza viruses isolated from pigs during 2009-2010 in five Brazilian states (Minas Gerais, Sao Paulo, Parana, Rio Grande do Sul, and Mato Grosso) were used. One human isolate, from a technician who became ill after visiting a swineherd going through a respiratory disease outbreak, was also used in the study. Phylogenetic analysis for the HA and NA genes and hemagglutinin amino acid sequence alignment were performed. Results All isolates clustered with pandemic H1N1 2009 (pH1N1) viruses and appeared to have a common ancestor. Genetic diversity was higher in the HA than in the NA gene, and the amino acid substitution S203T in one of HA's antigenic sites was found in most of the samples. The human isolate was more related to swine isolates from the same herd visited by the technician than to other human isolates, suggesting swine-to-human transmission. Conclusion Our results show that pH1N1 was disseminated and the predominant subtype in Brazilian pigs in 2009-2010

Comparison of the efficacy of a commercial inactivated influenza A/H1N1/pdm09 virus (pH1N1) vaccine and two experimental M2e-based vaccines against pH1N1 challenge in the growing pig model

<div><p>Swine influenza A viruses (IAV-S) found in North American pigs are diverse and the lack of cross-protection among heterologous strains is a concern. The objective of this study was to compare a commercial inactivated A/H1N1/pdm09 (pH1N1) vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e) epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit particle vaccine (NvParticle/M2e) or a subunit complex-based vaccine (NvComplex/M2e) or intramuscularly with a commercial inactivated vaccine (Inact/pH1N1). At 7 weeks of age, the pigs were challenged with pH1N1 virus or sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc). At the time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1 hemagglutination inhibition (HI) titers compared to all other groups, and M2e-specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e pigs with significantly higher group means in the NvComplex/M2e group compared to SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple consolidated areas typical of IAV infection and were similar for NvParticle/M2e, NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a commercial Inact/pH1N1 specific vaccine effectively protected pigs against homologous challenge as evidenced by reduced clinical signs, virus shedding in nasal secretions and oral fluids and reduced macroscopic and microscopic lesions whereas intranasal vaccination with experimental M2e epitope-based subunit vaccines did not. The results further highlight the importance using IAV-S type specific vaccines in pigs.</p></div