A Single Dose of a DNA Vaccine Encoding Apa Coencapsulated with 6,6′-Trehalose Dimycolate in Microspheres Confers Long-Term Protection against Tuberculosis in Mycobacterium bovis BCG-Primed Mice

Carlétti, Dyego de Souza; Fonseca, Denise Morais da; Gembre, Ana Flávia; Masson, Ana Paula; Campos, L. W.; Leite, Luciana C. C.; Pires, Andrea; Lannes-Vieira, Joseli; Silva, Célio Lopes; Bonato, Vânia Luiza Deperon; Horn, Cynthia

doi:10.1128/cvi.00148-13

Cited by 12 publications

(9 citation statements)

References 38 publications

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“…It remains to be seen whether nApa-boost during the expansion-phase, when higher BCG-load persists in the draining LNs and spleen 8 27 abolishes BCG-induced protection. However, no loss or improvement in BCG-induced protection was reported following microparticle-encapsulated apa genetic-boost during the expansion phase in a short-term protection experiment, and in fact, apa -boost modestly improved protection in the lung against chronic Mtb infection and prevented pathology 54 . In our study, subunit nApa-boost generated a strong booster effect despite targeting the same draining LNs where BCG persists 27 .…”

Section: Discussionmentioning

confidence: 87%

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis

Nandakumar

Kannanganat

Dobos

et al. 2016

Sci Rep

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Heterologous prime–boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32–52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime–Apa-subunit-boost strategy compared to Apa-subunit-prime–BCG-boost approach. However, parenteral BCG-prime–Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime–boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime–boost regimens against tuberculosis in humans.

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Section: Discussionmentioning

confidence: 87%

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis

Nandakumar

Kannanganat

Dobos

et al. 2016

Sci Rep

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“…With these nucleic-acid based vaccines, how the genetic material is introduced into the host is an important factor for consideration. While free DNA is able to transfect cells and methodologies have been devised to facilitate its uptake without a vector [72], it has been shown that vector-delivered DNA vaccines have a higher efficacy [73]. Introducing foreign free DNA to the host without any protective coating vector raises the potential for an improper immune response.…”

Section: Using Liposomes To Deliver Nucleic Acid-based Vaccinesmentioning

confidence: 99%

Designing liposomal adjuvants for the next generation of vaccines

Perrie

Crofts

Devitt

et al. 2016

Advanced Drug Delivery Reviews

108

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Liposomes not only offer the ability to enhance drug delivery, but can effectively act as vaccine delivery systems and adjuvants. Their flexibility in size, charge, bilayer rigidity and composition allow for targeted antigen delivery via a range of administration routes. In the development of liposomal adjuvants, the type of immune response promoted has been linked to their physico-chemical characteristics, with the size and charge of the liposomal particles impacting on liposome biodistribution, exposure in the lymph nodes and recruitment of the innate immune system. The addition of immunostimulatory agents can further potentiate their immunogenic properties. Here, we outline the attributes that should be considered in the design and manufacture of liposomal adjuvants for the delivery of sub-unit and nucleic acid based vaccines.

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“…Alanine is a major substrate for the hepatic synthesis of glucose, a significant energy substrate for leucocytes (Wannemacher et al, 1980). Alanine is also an important component of the glycoprotein (Carletti et al, 2013;El-Sabagh et al, 2014). Tyrosine, a product of phenylalanine degradation, is the immediate precursor for the synthesis of catecholamine hormones, indicating that an increased SNS activity and an up-regulation of catecholamine metabolism followed.…”

Section: The Effect Of Ee On Systemic Metabolitesmentioning

confidence: 99%

Echinacea purpurea Extract Affects the Immune System, Global Metabolome, and Gut Microbiome in Wistar Rats

Wang¹,

Hou²,

Lv³

et al. 2017

JAS

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Echinacea purpurea extract, a traditional herbal food additive with dual-purpose of medicine and edible material, has been widely used for the treatment and prevention of various infectious diseases, especially for children, old aged and immunocompromised patients. Although there were numerous reports suggested E. purpurea possessed immunostimulatory and antibacterial effects in vitro, the mechanisms underlying remained to be elucidated. This study employed immunologic factors analysis, GC-TOFMS based metabolomics and 16S-rRNA-sequencing microbiome profiling technologies to explore the effects of E. purpurea on young rats, a physiological insufficient immunity status, by compared with pidotimod treatment on young rats and adult animals. E. purpurea treatment significantly increased IL-2, decreased IL-6 and affect immunoglobulins in the spleen of young rats, indicating its promotion of cellular immunity. Both the immunologic factors and the global metabolome of E. purpurea treated young rats were close to the status of mature individuals. Results of 16S-rRNA-sequencing of ileum content together with co-metabolism metabolites demonstrated that E. purpurea changed gut microbiota structure characteristically as a reducing Firmicutes phylum, especially Lactobacillus, and a rising Actinobacteria phylum including Bifidobacterium. The results were concluded that E. purpurea could potentially promote the maturation of immune and metabolism of immature rats, and also affect gut flora structure.

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A Single Dose of a DNA Vaccine Encoding Apa Coencapsulated with 6,6′-Trehalose Dimycolate in Microspheres Confers Long-Term Protection against Tuberculosis in Mycobacterium bovis BCG-Primed Mice

Cited by 12 publications

References 38 publications

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis

Designing liposomal adjuvants for the next generation of vaccines

Echinacea purpurea Extract Affects the Immune System, Global Metabolome, and Gut Microbiome in Wistar Rats

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