Enhanced Priming of Adaptive Immunity by Mycobacterium smegmatis Mutants with High-Level Protein Secretion

Taylor, Natalie; Bahunde, Faith; Thompson, Afton L.; Yu, Jae Sung; Jacobs, William R.; Letvin, Norm L.; Haynes, Barton F.; Lee, Sunhee

doi:10.1128/cvi.00131-12

Cited by 3 publications

(2 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It also induced a significantly higher percentages of TNFa-and IFNg-producing CD8 þ T cells and antigenspecific CD8 þ T cells in TILs, indicating an effective CD8 þ T-cell stimulation by the Salmonella tumor vaccine. Insertion of heterologous genes to a live vaccine strain is a metabolic burden, and often leads to suboptimal antigen delivery and rapid loss of the expression vector, which decreases the efficiency of the vaccine (42). Attenuated Salmonella vaccine displaying heterologous antigen by MisL autotransporter required multiple immunizations due to the instability of the vaccine (35).…”

Section: Discussionmentioning

confidence: 99%

Combining DNA Vaccine and AIDA-1 in AttenuatedSalmonellaActivates Tumor-Specific CD4+ and CD8+ T-cell Responses

Zhao

Liu

et al. 2017

Cancer Immunology Research

View full text Add to dashboard Cite

Stimulation of tumor-specific responses in both CD4 þ and CD8 þ T cells has been a challenge for effective tumor vaccines. We designed a vaccine vector containing the AIDA-1 autotransporter and DNA vaccine elements, generating a murine melanoma vaccine that was delivered by the attenuated Salmonella strain SL7207. Growth of murine subcutaneous melanoma was significantly inhibited by intranasal immunization with the Salmonella tumor vaccine. The vaccine activated tumor-specific CD4 þ and CD8 þ T-cell responses, with increased T-cell proliferation, tumor antigen-specific Th1 cytokine production, increased percentages of tetramer positive cells, and cytotoxicity. CD4 þ or CD8 þ T-cell depletion resulted in the loss of antitumor activity of the Salmonella tumor vaccine, suggesting that the efficacy of the vaccine was dependent on both CD4 þ and CD8 þ T cells. Lung metastasis of the tumor was also inhibited by vaccine treatment. Similarly, the percentages of tumor-specific Th1 cytokine production by CD4 þ and CD8 þ T cells in the spleen, tumor, and bronchoalveolar lavage were increased after vaccine treatment. Tumor-specific proliferation of CD4 þ and CD8 þ T cells was also promoted by the vaccine. Tetramer staining and cytotoxicity assay showed enhanced tumor-specific CD8 þ T-cell response after vaccine treatment. Therefore, the Salmonella tumor vaccine could activate both tumor-specific CD4 þ and CD8 þ T-cell responses. This vaccine strategy may be widely applicable to the development of oral or nasal vaccines against tumors.

show abstract

Section: Discussionmentioning

confidence: 99%

Combining DNA Vaccine and AIDA-1 in AttenuatedSalmonellaActivates Tumor-Specific CD4+ and CD8+ T-cell Responses

Zhao

Liu

et al. 2017

Cancer Immunology Research

View full text Add to dashboard Cite

show abstract

“…However, genetically modified forms of M. smegmatis have recently been developed that show promising improvements. For example, transposon mutants of M. smegmatis that have enhanced protein secretion have been isolated, and these show improved priming of T cell responses against specific secreted protein antigens produced by the bacteria (115). Another interesting candidate vaccine strain was constructed by deletion of the chromosomal region encoding the ESX-3 type VII secretion system in M. smegmatis .…”

Section: Vaccine Strains Based On M Smegmatismentioning

confidence: 99%

Current efforts and future prospects in the development of live mycobacteria as vaccines

Saavedra-Ávila

Kennedy

et al. 2015

Expert Review of Vaccines

View full text Add to dashboard Cite

Summary The development of more effective vaccines against Mycobacterium tuberculosis (Mtb) remains a major goal in the effort to reduce the enormous global burden of disease caused by this pathogen. Whole-cell vaccines based on live mycobacteria with attenuated virulence represent an appealing approach, providing broad antigen exposure and intrinsic adjuvant properties to prime durable immune responses. However, designing vaccine strains with an optimal balance between attenuation and immunogenicity has proven to be extremely challenging. Recent basic and clinical research efforts have broadened our understanding of Mtb pathogenesis and created numerous new vaccine candidates that are designed to overcome different aspects of immune evasion by Mtb. In this review, we provide an overview of current efforts to create improved vaccines against tuberculosis based on modifications of live attenuated mycobacteria. In addition, we discuss the use of such vaccine strains as vectors for stimulating protective immunity against other infectious diseases and cancers.

show abstract

Discovery of Mycobacterium avium subsp. paratuberculosis Lytic Phages with Extensive Host Range Across Rapid- and Slow-Growing Pathogenic Mycobacterial Species

Golla,

Chaumontet,

Vande Voorde

et al. 2024

Antibiotics

View full text Add to dashboard Cite

Background/Objectives: Developing interventions for Johne’s disease, which focuses on controlling Mycobacterium avium subsp. paratuberculosis (MAP) in contaminated environments by treating infected cows and preventing transmission from diseased animals, is a critical priority. Bacteriophage (phage) therapy, an emerging biological intervention, offers a promising alternative for the treatment and management of MAP infections. Methods: In this study, we generated an MAP-specific lytic phage library aimed at characterizing the therapeutic potential of phages under environmental and biological conditions that mimic those encountered in infected cattle such as ruminal fluid, milk, colostrum, and the bovine intestinal epithelium, a key site of MAP colonization and, later, transmission. Results: Our library contains a diverse collection of phages that have demonstrated robust lytic activity against MAP. The host range of these phages was thoroughly assessed, revealing that several isolates produce clear plaques on a range of MAP strains, as well as other pathogenic non-tuberculous mycobacterial (NTM) species and M. tuberculosis strains. This broad host range expands the therapeutic potential of the phage collection, positioning it as a potential cross-species antimicrobial tool. In vitro tests under conditions replicating the rumen, milk, and colostrum environments show that selected phages maintain stability and lytic efficacy, even in the presence of complex biological fluids. Furthermore, a subset of these phages was capable of preventing MAP colonization and invasion in cultured bovine epithelial cells, suggesting their potential for direct prophylactic application in cattle. Conclusions. Our collection of MAP phages represents a valuable source that can be developed into probiotic-like preparations, offering a cost-effective solution for prophylaxis and control of Johne’s disease.

show abstract

Enhanced Priming of Adaptive Immunity by Mycobacterium smegmatis Mutants with High-Level Protein Secretion

Cited by 3 publications

References 61 publications

Combining DNA Vaccine and AIDA-1 in AttenuatedSalmonellaActivates Tumor-Specific CD4+ and CD8+ T-cell Responses

Combining DNA Vaccine and AIDA-1 in AttenuatedSalmonellaActivates Tumor-Specific CD4+ and CD8+ T-cell Responses

Current efforts and future prospects in the development of live mycobacteria as vaccines

Discovery of Mycobacterium avium subsp. paratuberculosis Lytic Phages with Extensive Host Range Across Rapid- and Slow-Growing Pathogenic Mycobacterial Species

Contact Info

Product

Resources

About