Mouse model characterisation for anthrax vaccine development: comparison of one inbred and one outbred mouse strain

In an attempt to improve upon a current mouse model of intestinal colonization by Escherichia coli O157:H7 used in this laboratory for vaccine development, nine clinical isolates of the pathogen were screened for their ability to persist in the intestinal tract of conventional adult CD-1 mice. None of the test isolates of E. coli O157:H7 were capable of colonizing these mice for a period of more than two weeks. Most of the isolates appeared to be benign for the experimental host, but one isolate was lethal. This virulence correlated with the ability of the latter isolate to produce large quantities of Shiga-like toxin 2 in vitro.

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Vaccination with Recombinant Cryptococcus Proteins in Glucan Particles Protects Mice against Cryptococcosis in a Manner Dependent upon Mouse Strain and Cryptococcal Species

mBio ◽

10.1128/mbio.01872-17 ◽

2017 ◽

Vol 8 (6) ◽

Cited By ~ 27

Author(s):

Charles A. Specht ◽

Chrono K. Lee ◽

Haibin Huang ◽

Maureen M. Hester ◽

Jianhua Liu ◽

...

Keyword(s):

Cryptococcus Neoformans ◽

Mouse Strain ◽

Subunit Vaccine ◽

Vaccine Development ◽

Inflammatory Responses ◽

Cryptococcus Gattii ◽

Candidate Vaccine ◽

Effective Vaccine ◽

Mouse Strains ◽

Vaccine Antigens

ABSTRACT Development of a vaccine to protect against cryptococcosis is a priority given the enormous global burden of disease in at-risk individuals. Using glucan particles (GPs) as a delivery system, we previously demonstrated that mice vaccinated with crude Cryptococcus -derived alkaline extracts were protected against lethal challenge with Cryptococcus neoformans and Cryptococcus gattii . The goal of the present study was to identify protective protein antigens that could be used in a subunit vaccine. Using biased and unbiased approaches, six candidate antigens (Cda1, Cda2, Cda3, Fpd1, MP88, and Sod1) were selected, recombinantly expressed in Escherichia coli , purified, and loaded into GPs. Three mouse strains (C57BL/6, BALB/c, and DR4) were then vaccinated with the antigen-laden GPs, following which they received a pulmonary challenge with virulent C. neoformans and C. gattii strains. Four candidate vaccines (GP-Cda1, GP-Cda2, GP-Cda3, and GP-Sod1) afforded a significant survival advantage in at least one mouse model; some vaccine combinations provided added protection over that seen with either antigen alone. Vaccine-mediated protection against C. neoformans did not necessarily predict protection against C. gattii . Vaccinated mice developed pulmonary inflammatory responses that effectively contained the infection; many surviving mice developed sterilizing immunity. Predicted T helper cell epitopes differed between mouse strains and in the degree to which they matched epitopes predicted in humans. Thus, we have discovered cryptococcal proteins that make promising candidate vaccine antigens. Protection varied depending on the mouse strain and cryptococcal species, suggesting that a successful human subunit vaccine will need to contain multiple antigens, including ones that are species specific. IMPORTANCE The encapsulated fungi Cryptococcus neoformans and Cryptococcus gattii are responsible for nearly 200,000 deaths annually, mostly in immunocompromised individuals. An effective vaccine could substantially reduce the burden of cryptococcosis. However, a major gap in cryptococcal vaccine development has been the discovery of protective antigens to use in vaccines. Here, six cryptococcal proteins with potential as vaccine antigens were expressed recombinantly and purified. Mice were then vaccinated with glucan particle preparations containing each antigen. Of the six candidate vaccines, four protected mice from a lethal cryptococcal challenge. However, the degree of protection varied as a function of mouse strain and cryptococcal species. These preclinical studies identify cryptococcal proteins that could serve as candidate vaccine antigens and provide a proof of principle regarding the feasibility of protein antigen-based vaccines to protect against cryptococcosis.

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Current State of Anthrax Vaccines and Key R&D Gaps Moving Forward

Microorganisms ◽

10.3390/microorganisms8050651 ◽

2020 ◽

Vol 8 (5) ◽

pp. 651 ◽

Cited By ~ 2

Author(s):

Adam Clark ◽

Daniel N. Wolfe

Keyword(s):

Vaccine Development ◽

The United States ◽

Post Exposure Prophylaxis ◽

Vaccine Research ◽

Anthrax Vaccine ◽

Current State ◽

Naturally Occurring ◽

Regulatory Frameworks ◽

Exposure Prophylaxis ◽

Anthrax Vaccines

A licensed anthrax vaccine has been available for pre-exposure prophylaxis in the United States since 1970, and it was approved for use as a post-exposure prophylaxis, in combination with antibiotic treatment, in 2015. A variety of other vaccines are available in other nations, approved under various regulatory frameworks. However, investments in anthrax vaccines continue due to the severity of the threat posed by this bacterium, as both a naturally occurring pathogen and the potential for use as a bioweapon. In this review, we will capture the current landscape of anthrax vaccine development, focusing on those lead candidates in clinical development. Although approved products are available, a robust pipeline of candidate vaccines are still in development to try to address some of the key research gaps in the anthrax vaccine field. We will then highlight some of the most pressing needs in terms of anthrax vaccine research.

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The role of mouse strain and Th1/Th2 immune responses in the α1,2-fucosyltransferase transgenic mouse model of colitis

Gastroenterology ◽

10.1016/s0016-5085(08)80603-8 ◽

2001 ◽

Vol 120 (5) ◽

pp. A123

Author(s):

Ashley M. Miller ◽

Peter R. Elliott ◽

William Connell ◽

Steven Brown ◽

Paul V. Desmond ◽

...

Keyword(s):

Mouse Model ◽

Immune Responses ◽

Transgenic Mouse ◽

Mouse Strain ◽

Transgenic Mouse Model

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Evaluation of Replication and Pathogenicity of Avian Influenza A H7 Subtype Viruses in a Mouse Model

Journal of Virology ◽

10.1128/jvi.00970-07 ◽

2007 ◽

Vol 81 (19) ◽

pp. 10558-10566 ◽

Cited By ~ 72

Author(s):

Tomy Joseph ◽

Josephine McAuliffe ◽

Bin Lu ◽

Hong Jin ◽

George Kemble ◽

...

Keyword(s):

Mouse Model ◽

Avian Influenza ◽

Neutralizing Antibodies ◽

Influenza A ◽

Vaccine Development ◽

Cross Reactivity ◽

Limited Information ◽

Antigenic Relatedness ◽

Kinetics Of ◽

H7 Subtype

ABSTRACT Avian influenza A H7 subtype viruses pose a significant threat to human health because of their ability to transmit directly from domestic poultry to humans and to cause disease and, sometimes, death. Although it is important to develop vaccines against viruses of this subtype, very limited information is available on the immune response and pathogenesis of H7 viruses in animal models such as mice and ferrets. Ten H7 viruses were selected for possible vaccine development on the basis of their phylogenetic relationships and geographical locations. The virulence of the 10 viruses for mice and the immunogenicity of the viruses in mice and ferrets were evaluated to study the extent of antigenic relatedness and the level of cross-reactivity of antibodies. Most of the viruses showed similar patterns of cross-reactivity with mouse and ferret antisera. The Eurasian viruses elicited broadly cross-reactive antibodies that neutralized viruses from both Eurasian and North American lineages, but the converse was not true. A subset of the viruses was also evaluated for the ability to replicate and cause disease in BALB/c mice following intranasal administration. H7 subtype viruses were able to infect mice without adaptation and manifested different levels of lethality and kinetics of replication. On the basis of phylogenetic data, induction of broadly cross-neutralizing antibodies in mouse and ferret antisera, and their ability to replicate in mice, we have selected A/Netherlands/219/03 (subtype H7N7) and A/chicken/BC/CN-7/04 (subtype H7N3) viruses for vaccine development. The mouse model can be used for the preclinical evaluation of these vaccines against H7 subtype viruses.

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Chromosome 1 Sequence Analysis of C57BL/6J-Chr1KM Mouse Strain

International Journal of Genomics ◽

10.1155/2017/1712530 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9

Author(s):

Fuyi Xu ◽

Tianzhu Chao ◽

Yiyin Zhang ◽

Shixian Hu ◽

Yuxun Zhou ◽

...

Keyword(s):

Mouse Strain ◽

Sequence Similarity ◽

Chromosome 1 ◽

Nucleotide Polymorphisms ◽

Mus Musculus Domesticus ◽

Entire Genome ◽

Functional Variants ◽

Outbred Mouse ◽

Km Mouse ◽

New Perspective

The Chinese Kunming (KM) mouse is a widely used outbred mouse stock in China. However, its genetic structure remains unclear. In this study, we sequenced the genome of the C57BL/6J-Chr1KM (B6-Chr1KM) strain, the chromosome 1 (Chr 1) of which was derived from one KM mouse. With 36.6× average coverage of the entire genome, 0.48 million single nucleotide polymorphisms (SNPs) and 96,679 indels were detected on Chr 1 through comparison with reference strain C57BL/6J. Moreover, 46,590 of them were classified as novel mutations. Further functional annotation identified 155 genes harboring potentially functional variants, among which 27 genes have been associated with human diseases. We then performed sequence similarity and Bayesian concordance analysis using the SNPs identified on Chr 1 and their counterparts in three subspecies, Mus musculus domesticus, M. m. musculus, and M. m. castaneus. Both analyses suggested that the Chr 1 sequence of B6-Chr1KM was predominantly derived from M. m. domesticus while 9.7% of the sequence was found to be from M. m. musculus. In conclusion, our analysis provided a detailed description of the genetic variations on Chr 1 of B6-Chr1KM and a new perspective on the subspecies origin of KM mouse which can be used to guide further genetic studies with this mouse strain.

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Introduction of two prolines and removal of the polybasic cleavage site leads to optimal efficacy of a recombinant spike based SARS-CoV-2 vaccine in the mouse model

10.1101/2020.09.16.300970 ◽

2020 ◽

Author(s):

Fatima Amanat ◽

Shirin Strohmeier ◽

Raveen Rathnasinghe ◽

Michael Schotsaert ◽

Lynda Coughlan ◽

...

Keyword(s):

Mouse Model ◽

Cleavage Site ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Middle Eastern ◽

Host Cells ◽

Spike Protein ◽

Optimized Design ◽

Angiotensin Converting Enzyme 2 ◽

Viral Target

AbstractThe spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the prime target for vaccine development. The spike protein mediates both binding to host cells and membrane fusion and is also so far the only known viral target of neutralizing antibodies. Coronavirus spike proteins are large trimers that are relatively instable, a feature that might be enhanced by the presence of a polybasic cleavage site in the SARS-CoV-2 spike. Exchange of K986 and V987 to prolines has been shown to stabilize the trimers of SARS-CoV-1 and the Middle Eastern respiratory syndrome coronavirus spikes. Here, we test multiple versions of a soluble spike protein for their immunogenicity and protective effect against SARS-CoV-2 challenge in a mouse model that transiently expresses human angiotensin converting enzyme 2 via adenovirus transduction. Variants tested include spike protein with a deleted polybasic cleavage site, the proline mutations, a combination thereof, as well as the wild type protein. While all versions of the protein were able to induce neutralizing antibodies, only the antigen with both a deleted cleavage site and the PP mutations completely protected from challenge in this mouse model.ImportanceA vaccine for SARS-CoV-2 is urgently needed. A better understanding of antigen design and attributes that vaccine candidates need to have to induce protective immunity is of high importance. The data presented here validates the choice of antigens that contain the PP mutation and suggests that deletion of the polybasic cleavage site could lead to a further optimized design.

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A Mutation in the Enamelin Gene in a Mouse Model

Journal of Dental Research ◽

10.1177/154405910708600815 ◽

2007 ◽

Vol 86 (8) ◽

pp. 764-768 ◽

Cited By ~ 18

Author(s):

H. Seedorf ◽

M. Klaften ◽

F. Eke ◽

H. Fuchs ◽

U. Seedorf ◽

...

Keyword(s):

Mouse Model ◽

Candidate Genes ◽

Mouse Chromosome ◽

Mouse Strain ◽

Autosomal Dominant ◽

Tooth Enamel ◽

Stop Codon ◽

Premature Stop Codon ◽

Amelogenesis Imperfecta ◽

Chromosome 5

Amelogenesis imperfecta is an inherited disorder affecting tooth enamel formation. We previously isolated a mouse strain with an amelogenesis imperfecta phenotype (ATE1 mice) from a dominant ethylnitrosourea screen and mapped the disease-causing defect to a 9-cM region of mouse chromosome 5. In the current study, we tested the hypothesis that there is a mutation in enamelin (ENAM) or ameloblastin (AMBN), both of which are located wihin the linkage region, by sequencing these two candidate genes. Analysis of our data shows that the amelogenesis imperfecta phenotype is linked to a C > T transition in exon 8 of the enamelin gene. The mutation predicts a C826T transition, which is present in the enamelin transcript and changes the glutamine (Gln) codon at position 176 into a premature stop codon (Gln176X). Conversely, no mutation could be detected in the ameloblastin gene. These results define the ATE1 mice as a model for local hypoplastic autosomal-dominant amelogenesis imperfecta (AIH2), which is caused by enamelin truncation mutations in humans.

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Genetically inbred Balb/C mice are more sensitive to an effect of flurazepam and more resistant to an effect of stress than a genetically outbred mouse strain

Epilepsy & Behavior ◽

10.1016/j.yebeh.2009.08.013 ◽

2009 ◽

Vol 16 (3) ◽

pp. 415-417 ◽

Cited By ~ 2

Author(s):

Jessica A. Burket ◽

John Mastropaolo ◽

Richard B. Rosse ◽

Stephen I. Deutsch

Keyword(s):

Mouse Strain ◽

Outbred Mouse

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