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In March 2013 it was reported by the World Health Organization (WHO) the first cases of human infections with avian influenza virus A (H7N9). From 2013 to December 2019, 1568 cases have been reported with 616 deaths. H7N9 infection has been associated with high morbidity and mortality rates, and vaccination is currently the most effective way to prevent infections and consequently flu-related severe illness. Developing and producing vaccines against pandemic influenza viruses is the main strategy for a response to a possible pandemic. This study aims to present the production of three industrial lots under current Good Manufacturing Practices (cGMP) of the active antigen used to produce the pandemic influenza vaccine candidate against A(H7N9). These batches were characterized and evaluated for quality standards and tested for immunogenicity in mice. The average yield was 173.50 ± 7.88 μg/mL of hemagglutinin and all the preparations met all the required specifications. The formulated H7N9 vaccine is poorly immunogenic and needs to be adjuvanted with an oil in water emulsion adjuvant (IB160) to achieve a best immune response, in a prime and in a boost scheme. These data are important for initial production planning and preparedness in the case of a H7N9 pandemic. • Pandemic influenza is a cyclic event in the humankind history, which can lead to millions of deaths. • Preparedness against a potential pandemic influenza is strategic to limit the spread of the disease as well as life savings. • Avian influenza virus A H7N9 infection has been associated with high morbidity and mortality rates and represents a potential pandemic threat. • Three industrial lots under current Good Manufacturing Practices (cGMP) of the active antigen used to prepare the pandemic influenza vaccine candidate against A (H7N9) were produced and characterized. • This production constitutes an important exercise for vaccine production planning and also represents stockpiling of the vaccine antigen for use in case of an H7N9 outbreak. [ABSTRACT FROM AUTHOR]

Abstract: The role of innate immune responses in protection against leptospirosis remains unclear. We examined the expression of the chemokines CCL2/JE (MCP-1), CCL3/MIP-1α (MIP-1α) and CXCL1/KC (IL-8) regarding resistance and susceptibility to leptospirosis in experimental mice models BALB/c and C3H/HeJ, respectively. A virulent strain of Leptospira interrogans serovar Copenhageni was used in this study. Twenty-five animals of each mouse strain of C3H/HeJ and BALB/c, were infected intraperitoneally with 106 cells. Five un-infected animals of each strain were kept as control. Mortality of C3H/HeJ mouse was observed while BALB/c mice were asymptomatic. The presence of leptospire DNA in tissues of infected animals was demonstrated by PCR. Chemokines were measured in serum, spleen, liver, kidney and lung of both strains of animals using immunoenzymatic assay (ELISA). Elevations in the levels of chemokines MCP-1 and IL-8 occurred in all organs and sera of C3H/HeJ and BALB/c infected mice. The levels of MIP-1α were lower when compared to MCP-1 and IL-8 in all analyzed organs, with a slight increase in liver and kidney. Our results indicate that the expression of inflammatory mediators can vary greatly, depending on the tissue and mouse strains. It is possible that the resistance to Leptospira can be partially correlated to the increase of MIP-1α observed in BALB/c mice, while an increasing and a sustained expression of MCP-1 and IL-8 in the lungs of C3H/HeJ mice can be correlated to the severity and progression of leptospirosis. [Copyright &y& Elsevier]

The bite of spiders of the genus Loxosceles can induce a variety of biological effects, including dermonecrosis and complement-dependent haemolysis. The aim of this study was to generate recombinant proteins from the Loxosceles spider gland to facilitate structural and functional studies in the mechanisms of loxoscelism. Using “Expressed Sequencing Tag” strategy of aleatory clones from, L. laeta venom gland cDNA library we have identified clones containing inserts coding for proteins with significant similarity with previously obtained N-terminus of sphingomyelinases from Loxosceles intermedia venom [1]. Clone H17 was expressed as a fusion protein containing a 6× His-tag at its N-terminus and yielded a 33 kDa protein. The recombinant protein was endowed with all biological properties ascribed to the whole L. laeta venom and sphingomyelinases from L. intermedia, including dermonecrotic and complement-dependent haemolytic activities. Antiserum raised against the recombinant protein recognised a 32-kDa protein in crude L. laeta venom and was able to block the dermonecrotic reaction caused by whole L. laeta venom. This study demonstrates conclusively that the sphingomyelinase activity in the whole venom is responsible for the major pathological effects of Loxosceles spider envenomation. [Copyright &y& Elsevier]

Leptospirosis is a global disease that affects humans and animals, impacting public health and the economy. The symptoms caused by Leptospira infection can vary from mild to severe, affecting liver, lungs, and kidneys. The host-pathogen interaction in leptospirosis is still poorly understood, but there is evidence for the role of the host immune response in the pathogenesis. Chemokines are a family of structurally-related low-molecular-mass proteins (8–14 kDa) that signal the recruitment of leukocytes. In this study the profile of 22 chemokines were evaluated in liver and kidney of three mice strains with different phenotypes of susceptibility to leptospirosis. We extended our previously reported observations showing that expression of chemokines with homeostatic function, activation and chemotaxis of leukocytes are essential to modulate and to induce resistance to leptospirosis. Our findings support that an early induction of CXC chemokines in resistant BALB/c mice can be associated with the control of the infection. The correlation of chemokine expression between liver and kidney observed in BALB/c suggests that a balance of chemokine induction in the organs may contribute to resistance to leptospirosis. [ABSTRACT FROM AUTHOR]