scholarly journals Purified Inactivated Zika Vaccine Candidates Afford Protection against Lethal Challenge in Mice

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Whitney R. Baldwin ◽  
Jill A. Livengood ◽  
Holli A. Giebler ◽  
Janae L. Stovall ◽  
Karen L. Boroughs ◽  
...  
Keyword(s):  
Lethal Challenge ◽  
Vaccine Candidates

Vaccine candidates generated by codon and codon pair deoptimization of enterovirus A71 protect against lethal challenge in mice

Vaccine ◽  
2021 ◽  
Vol 39 (12) ◽  
pp. 1708-1720
Author(s):  
Michelle Hui Pheng Lee ◽  
Chee Wah Tan ◽  
Han Kang Tee ◽  
Kien Chai Ong ◽  
I-Ching Sam ◽  
...  
Keyword(s):  
Lethal Challenge ◽  
Vaccine Candidates ◽  
Enterovirus A71 ◽  
Codon Pair

scholarly journals Protection from lethal challenge in a neonatal mouse model by circulating recombinant form coxsackievirus A16 vaccine candidates

2014 ◽  
Vol 95 (5) ◽  
pp. 1083-1093 ◽  
Author(s):  
Jingliang Li ◽  
Junliang Chang ◽  
Xin Liu ◽  
Jiaxin Yang ◽  
Haoran Guo ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vaccine Development ◽  
Lethal Dose ◽  
Neonatal Mouse ◽  
Recombinant Form ◽  
Control Group ◽  
Coxsackievirus A16 ◽  
Lethal Challenge ◽  
Vaccine Candidates

Circulating coxsackievirus A16 (CA16) is a major cause of hand, foot and mouth disease (HFMD) in South-east Asia. At present, there is no vaccine against CA16. Pathogenic animal models that are sensitive to diverse circulating CA16 viruses would be desirable for vaccine development and evaluation. In this study, we isolated and characterized several circulating CA16 viruses from recent HFMD patients. These CA16 viruses currently circulating in humans were highly pathogenic in a newly developed neonatal mouse model; we also observed and analysed the pathogenesis of representative circulating recombinant form CA16 viruses. An inactivated CA16 vaccine candidate, formulated with alum adjuvant and containing submicrogram quantities of viral proteins, protected neonatal mice born to immunized female mice from lethal-dose challenge with a series of CA16 viruses. Further analysis of humoral immunity showed that antibody elicited from both the immunized dams and their pups could neutralize various lethal viruses by a cytopathic effect in vitro. Moreover, viral titres and loads in the tissues of challenged pups in the vaccine group were far lower than those in the control group, and some were undetectable. This lethal-challenge model using pathogenic CA16 viruses and the vaccine candidates that mediated protection in this model could be useful tools for the future development and evaluation of CA16 vaccines.

Development and Characterization of Recombinant Vesicular Stomatitis Virus (rVSV)-based Bivalent Vaccine Against COVID-19 Delta Variant and Influenza Virus

2021 ◽  
Author(s):  
Zhujun Ao ◽  
Maggie Jing Ouyang ◽  
Titus Abiola Olukitibi ◽  
Bryce Warner ◽  
Robert Vendramelli ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Respiratory Infections ◽  
Convincing Evidence ◽  
Influenza Viruses ◽  
Lethal Challenge ◽  
Vaccine Candidates ◽  
Bivalent Vaccine ◽  
Wide Range

COVID-19 and influenza are both highly contagious respiratory diseases with a wide range of severe symptoms and cause great disease burdens globally. It has become very urgent and important to develop a bivalent vaccine that is able to target these two infectious diseases simultaneously. In this study, we generated three attenuated replicating recombinant VSV (rVSV) vaccine candidates. These rVSV-based vaccines co-express SARS-CoV-2 Delta variant spike protein (SP) or the receptor binding domain (RBD) and four copies of the highly conserved M2 ectodomain (M2e) of influenza A fused with the Ebola glycoprotein DC-targeting/activation domain. Animal studies have shown that immunization with these bivalent rVSV vaccines induced efficient but variable levels of humoral and cell-mediated immune responses against both SARS-CoV-2 and influenza M2e protein. Significantly, our vaccine candidates induced production of high levels of neutralizing antibodies that protected cells against SARS-CoV-2 Delta and other SP-pseudovirus infections in culture. Furthermore, vaccination with the bivalent VSV vaccine via either intramuscular or intranasal route efficiently protected mice from the lethal challenge of H1N1 and H3N2 influenza viruses and significantly reduced viral load in the lungs. These studies provide convincing evidence for the high efficacy of this bivalent vaccine to prevent influenza replication and initiate robust immune responses against SARS-CoV-2 Delta variants. Further investigation of its efficacy to protect against SARS-CoV-2 Delta variants will provide substantial evidence for new avenues to control two contagious respiratory infections, COVID-19 and influenza.

scholarly journals Proteomics-Based Identification of Anchorless Cell Wall Proteins as Vaccine Candidates against Staphylococcus aureus

2009 ◽  
Vol 77 (7) ◽  
pp. 2719-2729 ◽  
Author(s):  
Eva Glowalla ◽  
Bettina Tosetti ◽  
Martin Krönke ◽  
Oleg Krut
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Survival Rates ◽  
Proteome Analysis ◽  
Surface Proteins ◽  
Human Neutrophils ◽  
Cell Wall Proteins ◽  
Lethal Challenge ◽  
Vaccine Candidates

ABSTRACT Staphylococcus aureus is an important human pathogen with increasing clinical impact due to the extensive spread of antibiotic-resistant strains. Therefore, development of a protective polyvalent vaccine is of great clinical interest. We employed an intravenous immunoglobulin (IVIG) preparation as a source of antibodies directed against anchorless S. aureus surface proteins for identification of novel vaccine candidates. In order to identify such proteins, subtractive proteome analysis (SUPRA) of S. aureus anchorless cell wall proteins was performed. Proteins reacting with IVIG but not with IVIG depleted of S. aureus-specific opsonizing antibodies were considered vaccine candidates. Nearly 40 proteins were identified by this preselection method using matrix-assisted laser desorption ionization—time of flight analysis. Three of these candidate proteins, enolase (Eno), oxoacyl reductase (Oxo), and hypothetical protein hp2160, were expressed as glutathione S-transferase fusion proteins, purified, and used for enrichment of corresponding immunoglobulin Gs from IVIG by affinity chromatography. Use of affinity-purified anti-Eno, anti-Oxo, and anti-hp2160 antibodies resulted in opsonization, phagocytosis, and killing of S. aureus by human neutrophils. High specific antibody titers were detected in mice immunized with recombinant antigens. In mice challenged with bioluminescent S. aureus, reduced staphylococcal spread was measured by in vivo imaging. The recovery of S. aureus CFU from organs of immunized mice was diminished 10- to 100-fold. Finally, mice immunized with hp2160 displayed statistically significant higher survival rates after lethal challenge with clinically relevant S. aureus strains. Taken together, our data suggest that anchorless cell wall proteins might be promising vaccine candidates and that SUPRA is a valuable tool for their identification.

scholarly journals Zika Virus Attenuation by Codon Pair Deoptimization Induces Sterilizing Immunity in Mouse Models

2018 ◽  
Vol 92 (17) ◽  
Author(s):  
Penghui Li ◽  
Xianliang Ke ◽  
Ting Wang ◽  
Zhongyuan Tan ◽  
Dan Luo ◽  
...  
Keyword(s):  
Antibody Titer ◽  
Zika Virus ◽  
Mammalian Cells ◽  
Neutralizing Antibody ◽  
Wild Type ◽  
Complete Protection ◽  
Lethal Challenge ◽  
Vaccine Candidates ◽  
Codon Pair ◽  
Sterilizing Immunity

ABSTRACTZika virus (ZIKV) infection during the large epidemics in the Americas is related to congenital abnormities or fetal demise. To date, there is no vaccine, antiviral drug, or other modality available to prevent or treat Zika virus infection. Here we designed novel live attenuated ZIKV vaccine candidates using a codon pair deoptimization strategy. Three codon pair-deoptimized ZIKVs (Min E, Min NS1, and Min E+NS1) werede novosynthesized and recovered by reverse genetics and contained large amounts of underrepresented codon pairs in the E gene and/or NS1 gene. The amino acid sequence was 100% unchanged. The codon pair-deoptimized variants had decreased replication fitness in Vero cells (Min NS1 ≫ Min E > Min E+NS1), replicated more efficiently in insect cells than in mammalian cells, and demonstrated diminished virulence in a mouse model. In particular, Min E+NS1, the most restrictive variant, induced sterilizing immunity with a robust neutralizing antibody titer, and a single immunization achieved complete protection against lethal challenge and vertical ZIKV transmission during pregnancy. More importantly, due to the numerous synonymous substitutions in the codon pair-deoptimized strains, reversion to wild-type virulence through gradual nucleotide sequence mutations is unlikely. Our results collectively demonstrate that ZIKV can be effectively attenuated by codon pair deoptimization, highlighting the potential of Min E+NS1 as a safe vaccine candidate to prevent ZIKV infections.IMPORTANCEDue to unprecedented epidemics of Zika virus (ZIKV) across the Americas and the unexpected clinical symptoms, including Guillain-Barré syndrome, microcephaly, and other birth defects in humans, there is an urgent need for ZIKV vaccine development. Here we provided the first attenuated versions of ZIKV with two important genes (E and/or NS1) that were subjected to codon pair deoptimization. Compared to parental ZIKV, the codon pair-deoptimized ZIKVs were mammal attenuated and preferred insect to mammalian cells. Min E+NS1, the most restrictive variant, induced sterilizing immunity with a robust neutralizing antibody titer and achieved complete protection against lethal challenge and vertical virus transmission during pregnancy. More importantly, the massive synonymous mutational approach made it impossible for the variant to revert to wild-type virulence. Our results have proven the feasibility of codon pair deoptimization as a strategy to develop live attenuated vaccine candidates against flaviviruses such as ZIKV, Japanese encephalitis virus, and West Nile virus.

Role of Artesunate in Potentiation of β-lactam Against Methicillin Resistant Staphylococcus aureus (MRSA) Isolated from Bovine Mastitis and its Histopathology Impact In-Vivo Study

2020 ◽  
Keyword(s):  
Clavulanic Acid ◽  
Resistance Mechanism ◽  
Bovine Mastitis ◽  
Lethal Challenge ◽  
Experimental Procedure ◽  
Appropriate Treatment ◽  
Amoxicillin Clavulanic Acid ◽  
Mrsa Infection

This article discusses the augmenting influence of Artesunate (ART) in combination with β-lactams (amoxicillin/clavulanic acid) antibiotic in sepsis mice models infected by a lethal challenge dose of live coagulase positive enterotoxigenic (Sec) MRSA that was isolated from a case of chronic bovine mastitis. The main goal is to find an appropriate treatment to overcome resistance mechanism of MRSA towards β-lactams antibiotic. Fifty healthy adult Swiss mice divided into 5 equal groups were used in the experimental procedure. The infected group that treated with both ART and β-lactams (amoxicillin/clavulanic acid) antibiotic revealed complete inhibition of MRSA count with complete normal macroscopic and histopathological features. We suggest that ART can potentiate the antibacterial action of β-lactams (amoxicillin/Clavulanic) acid against MRSA infection. The combination of ART and antibiotic can overcome MRSA resistance mechanism and so could be considered a novel candidate to overcome mastitis and/or sepsis caused by MRSA.

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