Safety and Immunogenicity of the
 Mycobacterium tuberculosis
 Δ
 lysA
 Δ
 panCD
 Vaccine in Domestic Cats Infected with Feline Immunodeficiency Virus

Zimmerman, Dawn; Waters, W. Ray; Lyashchenko, Konstantin P.; Nonnecke, Brian J.; Armstrong, Douglas L.; Jacobs, William R.; Larsen, Michelle H.; Egan, Erin A.; Dean, Gregg A.

doi:10.1128/cvi.00396-08

Cited by 7 publications

(4 citation statements)

References 10 publications

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“…The construction, attenuations and safety profiles of the Mtb H37Rv-derived vaccine strains mc 2 6435 and mc 2 6020 have been described previously (15, 25–30). Briefly, in strain mc 2 6020, the panCD and lysA loci were deleted to generate a highly replication-attenuated double-auxotroph strain.…”

Section: Methodsmentioning

confidence: 99%

A neonatal oral Mycobacterium tuberculosis-SIV prime/intramuscular MVA-SIV boost combination vaccine induces both SIV and Mtb-specific immune responses in infant macaques

Jensen

Pena

Wilson

et al. 2013

Trials in Vaccinology

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Mother-to-child-transmission of HIV by breast-feeding remains a major obstacle in the eradication of HIV infection. Compared to adults, HIV-infected infants have more rapid disease and show higher susceptibility to co-infections like tuberculosis (TB). Although the Bacille Calmette-Guérin vaccine can be administered at birth to protect against TB, BCG can disseminate in HIV-infected infants and increase mortality. Thus, a pediatric combination vaccine to stop both HIV and TB infection in infants is urgently needed. Towards the goal of developing a pediatric combination HIV-TB vaccine to prevent both oral HIV acquisition by breast-feeding and TB infection, we tested and optimized an immunization regimen using a novel live attenuated Mycobacterium tuberculosis vaccine engineered to express simian immunodeficiency (SIV) antigens followed by heterologous MVA-SIV boosting in the infant macaque model. A single oral dose of the attenuated Mtb-SIV vaccine strain mc26435 during the first week of life was sufficient to induce persistent TB-specific immune responses. SIV-specific immunity was induced at low but comparable magnitudes after oral or intradermal priming, and was enhanced following MVA-SIV boosts. T cell responses were most pronounced in intestinal tissues and oral lymph nodes. Importantly, in addition to plasma SIV-specific IgG and IgA antibodies, infant macaques developed mucosal SIV-specific IgA in saliva and intestinal IgA and IgG. While future SIV and Mtb challenge studies will be needed to determine the protective efficacy of the Mtb-SIV / MVA-SIV vaccine, infants at high risk for oral HIV acquisition by breast-feeding and TB infection could profoundly benefit from an effective combination vaccine.

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Section: Methodsmentioning

confidence: 99%

A neonatal oral Mycobacterium tuberculosis-SIV prime/intramuscular MVA-SIV boost combination vaccine induces both SIV and Mtb-specific immune responses in infant macaques

Jensen

Pena

Wilson

et al. 2013

Trials in Vaccinology

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“…In fact, we discovered that M. tuberculosis mutants defective in making the amino acid lysine (37) or the vitamin pantothenate also were highly attenuated (38). After constructing double auxotroph of mutants of M. tuberculosis , we demonstrated that they are very safe and have the ability to generate protection comparable to BCG (39–42). …”

Section: Overview Of Key Mutations That Facilitated Gene Transfer In mentioning

confidence: 99%

Gene Transfer in Mycobacterium tuberculosis : Shuttle Phasmids to Enlightenment

Jacobs

2014

Microbiol Spectr

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Infectious diseases have plagued humankind throughout history and have posed serious public health problems. Yet vaccines have eradicated smallpox and antibiotics have drastically decreased the mortality rate of many infectious agents. These remarkable successes in the control of infections came from knowing the causative agents of the diseases, followed by serendipitous discoveries of attenuated viruses and antibiotics. The discovery of DNA as genetic material and the understanding of how this information translates into specific phenotypes have changed the paradigm for developing new vaccines, drugs, and diagnostic tests. Knowledge of the mechanisms of immunity and mechanisms of action of drugs has led to new vaccines and new antimicrobial agents. The key to the acquisition of the knowledge of these mechanisms has been identifying the elemental causes (i.e., genes and their products) that mediate immunity and drug resistance. The identification of these genes is made possible by being able to transfer the genes or mutated forms of the genes into causative agents or surrogate hosts. Such an approach was limited in Mycobacterium tuberculosis by the difficulty of transferring genes or alleles into M. tuberculosis or a suitable surrogate mycobacterial host. The construction of shuttle phasmids—chimeric molecules that replicate in Escherichia coli as plasmids and in mycobacteria as mycobacteriophages—was instrumental in developing gene transfer systems for M. tuberculosis. This review will discuss M. tuberculosis genetic systems and their impact on tuberculosis research. “I had to know my enemy in order to prevail against him.”Nelson Mandela

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“…Diagnosis is based on clinical examination, imaging, biopsy with histopathologic examination, culture of aspirates or tissues, and specific immune-based blood assays ( 4 , 8 , 9 ). Intradermal skin tests are generally unreliable for diagnosing tuberculosis in cats ( 10 ).…”

mentioning

confidence: 99%

“…Before implementation of bovine tuberculosis control programs and wide-scale pasteurization of milk, alimentary tract disease was the most common form of tuberculosis in cats ( 7 ); today, lymphadenopathy and cutaneous forms are more common ( 4 ). Diagnosis is based on clinical examination, imaging, biopsy with histopathologic examination, culture of aspirates or tissues, and specific immune-based blood assays ( 4 , 8 , 9 ). Intradermal skin tests are generally unreliable for diagnosing tuberculosis in cats ( 10 ).…”

mentioning

confidence: 99%

Mycobacterium bovisInfection in Humans and Cats in Same Household, Texas, USA, 2012

Ramdas¹,

Lyashchenko²,

Greenwald³

et al. 2015

Emerg. Infect. Dis.

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Safety and Immunogenicity of the Mycobacterium tuberculosis Δ lysA Δ panCD Vaccine in Domestic Cats Infected with Feline Immunodeficiency Virus

Cited by 7 publications

References 10 publications

A neonatal oral Mycobacterium tuberculosis-SIV prime/intramuscular MVA-SIV boost combination vaccine induces both SIV and Mtb-specific immune responses in infant macaques

A neonatal oral Mycobacterium tuberculosis-SIV prime/intramuscular MVA-SIV boost combination vaccine induces both SIV and Mtb-specific immune responses in infant macaques

Gene Transfer in Mycobacterium tuberculosis : Shuttle Phasmids to Enlightenment

Mycobacterium bovisInfection in Humans and Cats in Same Household, Texas, USA, 2012

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