ABSTRACT
Yellow fever (YF) is a disease caused by the homonymous flavivirus that can be prevented by a vaccine containing attenuated viruses. Since some individuals cannot receive this vaccine, the development of alternatives is desirable. Here, we developed a recombinant baculovirus (rBV) surface display platform utilizing a chimeric E-NS1 protein as a vaccine candidate. A pBacPAK9 vector containing the baculoviral GP64 signal peptide, the YFV prM, E, NS1 and the ectodomain of VSV-G sequences was synthesized. This transfer plasmid and the bAcGOZA bacmid were cotransfected into Sf9 cells, and an rBV-E-NS1 was obtained, which was characterized by PCR, WB, IFI and FACS analysis. Mice immunized with rBV-E-NS1 elicited a specific humoral and cellular immune response and were protected after YFV infection. In summary, we have developed an rBV that expresses YFV major antigen proteins on its surface, which opens new alternatives that can be tested in a mouse model.
ABSTRACT
The spirochetal bacteria Leptospira spp. are causative agents of leptospirosis, a globally neglected and reemerging zoonotic disease. Infection with these pathogens may lead to an acute and potentially fatal disease but also to chronic asymptomatic renal colonization. Both forms of disease demonstrate the ability of leptospires to evade the immune response of their hosts. In this review, we aim first to recapitulate the knowledge and explore the controversial data about the opsonization, recognition, intracellular survival, and killing of leptospires by scavenger cells, including platelets, neutrophils, macrophages, and dendritic cells. Second, we will summarize the known specificities of the recognition or escape of leptospire components (the so-called microbial-associated molecular patterns; MAMPs) by the pattern recognition receptors (PRRs) of the Toll-like and NOD-like families. These PRRs are expressed by phagocytes, and their stimulation by MAMPs triggers pro-inflammatory cytokine and chemokine production and bactericidal responses, such as antimicrobial peptide secretion and reactive oxygen species production. Finally, we will highlight recent studies suggesting that boosting or restoring phagocytic functions by treatments using agonists of the Toll-like or NOD receptors represents a novel prophylactic strategy and describe other potential therapeutic or vaccine strategies to combat leptospirosis.
Subject(s)
Leptospira/physiology , Leptospirosis/immunology , Macrophages/immunology , NLR Proteins/metabolism , Neutrophils/immunology , Phagocytes/immunology , Toll-Like Receptors/metabolism , Animals , Humans , Immune Evasion , Immunity, Innate , PhagocytosisABSTRACT
Bovine herpesvirus-1 (BoHV-1) infection is distributed worldwide and the development of new tools to fight against this pathogen has become extremely important. In this work a recombinant modified vaccinia virus Ankara (MVA) vector expressing the secreted version of glycoprotein D, MVA-gDs, was obtained and evaluated as a candidate vaccine. First, the correct expression, antigenicity, and N-glycosylation of glycoprotein D were confirmed by molecular techniques. Then MVA-gDs was used as parenteral immunogen in BALB/C mice in which a specific anti-gD humoral immune response was induced and maintained for 7 mo. Two doses of MVA-gDs supplemented with cholera toxin delivered by intranasal immunization induced IgA anti-gD humoral immune responses in nasal and bronchopulmonary washes, as well as IgG anti-gD antibodies in serum samples. In order to evaluate the protection conferred by MVA-gDs immunization, a rabbit BoHV-1 challenge assay was performed. A shorter viral excretion period and a reduction in the number of animals shedding BoHV-1 was observed in the group immunized with recombinant MVA-gDs. In conclusion our data encourage further studies to evaluate MVA-gDs, alone or combined with other immunogens, as a candidate vaccine for BoHV-1.