Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector?

Pelizon, A. C.; Martins, Denizar Cruz; Zorzella-Pezavento, Sofia Fernanda Gonçalves; Seger, Juliana; Justulin, Luis Antônio; Fonseca, Denise Morais da; Santos, Ramon Rodrigues dos; Masson, Ana Paula; Silva, Célio Lopes; Sartori, Alexandrina

doi:10.1111/j.1365-3083.2009.02352.x

Cited by 6 publications

(5 citation statements)

References 39 publications

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“…Not all immunogenic antigens can be used for vaccine development. For example, M. tuberculosis LppX ( 21 ) and Hsp65 ( 22 ) are both highly immunogenic but not protective against tuberculosis. To the best of our knowledge, Protegen is the first web-based, publically available database and analysis system that targets for the curation and analysis of protective antigens.…”

Section: Discussionmentioning

confidence: 99%

Protegen: a web-based protective antigen database and analysis system

Yang¹,

Sayers²,

Xiang³

et al. 2010

Nucleic Acids Research

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Protective antigens are specifically targeted by the acquired immune response of the host and are able to induce protection in the host against infectious and non-infectious diseases. Protective antigens play important roles in vaccine development, as biological markers for disease diagnosis, and for analysis of fundamental host immunity against diseases. Protegen is a web-based central database and analysis system that curates, stores and analyzes protective antigens. Basic antigen information and experimental evidence are curated from peer-reviewed articles. More detailed gene/protein information (e.g. DNA and protein sequences, and COG classification) are automatically extracted from existing databases using internally developed scripts. Bioinformatics programs are also applied to compute different antigen features, such as protein weight and pI, and subcellular localizations of bacterial proteins. Presently, 590 protective antigens have been curated against over 100 infectious diseases caused by pathogens and non-infectious diseases (including cancers and allergies). A user-friendly web query and visualization interface is developed for interactive protective antigen search. A customized BLAST sequence similarity search is also developed for analysis of new sequences provided by the users. To support data exchange, the information of protective antigens is stored in the Vaccine Ontology (VO) in OWL format and can also be exported to FASTA and Excel files. Protegen is publically available at http://www.violinet.org/protegen.

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Section: Discussionmentioning

confidence: 99%

Protegen: a web-based protective antigen database and analysis system

Yang¹,

Sayers²,

Xiang³

et al. 2010

Nucleic Acids Research

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“…To construct the DNA vaccine, the functional pVax:hsp65 plasmid [50] was digested with 10 units of BamHI (Biolabs, England) and 20 units of NotI (Invitrogen, Carlsbad, CA, USA) restriction enzymes. A 3.3 Kb fragment corresponding to the Mycobaterium leprae hsp65 gene was obtained with cytomegalovirus (CMV) intron A.…”

Section: Dna Vaccine Construction: Recombinant L Delbrueckii Cidca 133 (Pexu:hsp65)mentioning

confidence: 99%

Intake of Lactobacillus delbrueckii (pExu:hsp65) Prevents the Inflammation and the Disorganization of the Intestinal Mucosa in a Mouse Model of Mucositis

et al. 2021

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5-Fluorouracil (5-FU) is an antineoplastic drug that causes, as a side effect, intestinal mucositis, acute inflammation in the small bowel. The Heat Shock Protein (Hsp) are highly expressed in inflammatory conditions, developing an important role in immune modulation. Thus, they are potential candidates for the treatment of inflammatory diseases. In the mucositis mouse model, the present study aimed to evaluate the beneficial effect of oral administration of milk fermented by Lactobacillus delbrueckii CIDCA 133 (pExu:hsp65), a recombinant strain. This approach showed increased levels of sIgA in the intestinal fluid, reducing inflammatory infiltrate and intestinal permeability. Additionally, the histological score was improved. Protection was associated with a reduction in the gene expression of pro-inflammatory cytokines such as Tnf, Il6, Il12, and Il1b, and an increase in Il10, Muc2, and claudin 1 (Cldn1) and 2 (Cldn2) gene expression in ileum tissue. These findings are corroborated with the increased number of goblet cells, the electronic microscopy images, and the reduction of intestinal permeability. The administration of milk fermented by this recombinant probiotic strain was also able to reverse the high levels of gene expression of Tlrs caused by the 5-FU. Thus, the rCIDCA 133:Hsp65 strain was revealed to be a promising preventive strategy for small bowel inflammation.

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“…The first step was to assess whether intradermal injection of rDIsSIV gag induces Gag‐specific IFN‐γ‐producing CD8 + T cells in mucosal and systemic tissues. Although the BCG vector itself non‐specifically enhances the levels of some cytokines [33], the DIs empty vector and rDIsLacZ scarcely stimulated IFN‐γ‐production, and the number of IFN‐γ SFC per 10 6 cells was less than 32 in intradermally injected mice [14] and intramuscularly injected non‐human primates [12] in our previous studies. Moreover, the calculated number of Gag‐specific IFN‐γ SFC from naive mice was < 15 per 10 6 CD8 + T cells.…”

Section: Resultsmentioning

confidence: 99%

Intradermal Delivery of Recombinant Vaccinia Virus Vector DIs Induces Gut‐Mucosal Immunity

et al. 2010

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Antigen‐specific mucosal immunity is generally induced by the stimulation of inductive mucosal sites. In this study, we found that the replication‐deficient vaccinia virus vector, DIs, generates antigen‐specific mucosal immunity and systemic responses. Following intradermal injection of recombinant DIs expressing simian immunodeficiency virus gag (rDIsSIVgag), we observed increased levels of SIV p27‐specific IgA and IgG antibodies in faecal extracts and plasma samples, and antibody‐forming cells in the intestinal mucosa and spleen of C57BL/6 mice. Antibodies against p27 were not detected in nasal washes, saliva, and vaginal washes. The enhanced mucosal and systemic immunity persisted for 1 year of observation. Induction of Gag‐specific IFN‐γ spot‐forming CD8+ T cells in the spleen, small intestinal intraepithelial lymphocytes, and submandibular lymph nodes was observed in the intradermally injected mice. Heat‐inactivated rDIsSIVgag rarely induced antigen‐specific humoral and T‐helper immunity. Moreover, rDIsSIVgag was detected in MHC class II IA antigen‐positive (IA+) cells at the injection site. Consequently, intradermal delivery of rDIs effectively induces antigen‐specific humoral and cellular immunity in gut‐mucosal tissues of mice. Our data suggest that intradermal injection of an rDIs vaccine may be useful against mucosally transmitted pathogens.

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Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector?

Cited by 6 publications

References 39 publications

Protegen: a web-based protective antigen database and analysis system

Protegen: a web-based protective antigen database and analysis system

Intake of Lactobacillus delbrueckii (pExu:hsp65) Prevents the Inflammation and the Disorganization of the Intestinal Mucosa in a Mouse Model of Mucositis

Intradermal Delivery of Recombinant Vaccinia Virus Vector DIs Induces Gut‐Mucosal Immunity

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