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Principal Investigator: Clayton C Caswell
Organization: VIRGINIA POLYTECHNIC INST AND ST UNIV
Fiscal Year: 2021
Award: $77,739
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
Brucella spp. are bacteria that naturally infect a variety of domesticated and wild animals leading to
abortions and sterility, and these bacteria are also capable of causing debilitating human infections, which
often result from human exposure to infected animals and animal products. Brucella spp. are considered
threats as potential biological weapons. Importantly, antibiotic treatment against brucellosis is prone to disease
relapse, and there is currently no safe and effective vaccine to protect humans against infection with Brucella.
The brucellae are intracellular pathogens that reside within immune cells called macrophages where they
replicate in a specialized compartment, and the capacity of Brucella to survive and replicate within
macrophages is essential to their ability to cause disease. Over the last few years, our laboratory has
characterized genetic pathways that are critical for the intracellular survival and pathogenesis of Brucella
strains, and specifically, we have identified small regulatory RNAs (sRNAs) that are essential for Brucella
virulence.
Preliminary experiments have demonstrated that a family of sRNAs, called the AbcRs is required for the
ability of B. abortus to chronically infect mice. When these genes encoding these two sRNAs (i.e., AbcR1 and
AbcR2) are deleted, the resulting strain is highly attenuated, and moreover, we have determined that this
deletion strain produces extremely high levels of Brucella immunogenic proteins. We hypothesize that the
abcR1 abcR2 deletion strain can serve as a highly effective live, attenuation vaccine against B. abortus
challenge, and the pilot studies outlined in this application will test this hypothesis. In the end, the information
gleaned from these studies may be used to develop an effective vaccine against human Brucella infection.
Terms: <Animal Model><Animal Models and Related Studies><Animals><Antibiotic Agents><Antibiotic Drugs><Antibiotic Therapy><Antibiotic Treatment><Antibiotics><Antigen Presentation><Attenuated><Attenuated Vaccines><B abortus><B. abortus><Bacteria><Binding><Biological Function><Biological Process><Brucella><Brucella abortus><Brucella melitensis biovar abortus><Brucellosis><Cell Body><Cell model><Cells><Cellular model><Chronic><Critical Paths><Critical Pathways><Data><Dendritic Cells><Development><Disease><Disorder><Domestic Animals><Exposure to><Family><Future><Gene Expression><Gene Transcription><Genes><Genetic><Genetic Transcription><Glean><Goals><Human><Immune><Immune Cell Activation><Immune response><Immune system><Immunes><Immunological response><Immunomodulation><Infection><Innate Immune System><Laboratories><Live-attenuated Vaccine><Malta Fever><Mediating><Messenger RNA><Mice><Mice Mammals><Miscellaneous Antibiotic><Modern Man><Molecular Interaction><Murine><Mus><Mφ><Non-Polyadenylated RNA><Pathogenesis><Pilot Projects><Procedures><Production><Proteins><RNA><RNA Expression><RNA Gene Products><Recurrent disease><Relapsed Disease><Research><Ribonucleic Acid><Sterility><T-Cell Proliferation><Testing><Transcript><Transcription><Undulant Fever><Vaccinated><Vaccination><Vaccines><Veiled Cells><Virulence><Virulent><Wild Animals><Work><abortion><adaptive immunity><allergic/immunologic body system><allergic/immunologic organ system><attenuation><bacterial disease treatment><bacterial infectious disease treatment><biological weapon><bioweapon><combat><design><designing><developmental><domesticated animal><efficacy analysis><efficacy assessment><efficacy evaluation><efficacy examination><evaluate efficacy><examine efficacy><experiment><experimental research><experimental study><exposed human population><flu><host colonization><host response><human exposure><immune activation><immune modulation><immune regulation><immune system response><immunogenic><immunogenicity><immunologic reactivity control><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><improved><in vivo><live vaccine><live vaccines><mRNA><macrophage><model of animal><model organism><mouse model><murine model><new vaccines><next generation vaccines><novel><novel vaccines><pathogen><pilot study><prevent><preventing><sterile><vaccination study><vaccination trial><vaccine study><vaccine trial>