Immunogencity of antigens from Mycobacterium tuberculosis self-assembled as particulate vaccines

Reyes, Patricia Rubio; Parlane, Natalie A.; Wedlock, D. Neil; Rehm, Bernd H. A.

doi:10.1016/j.ijmm.2016.10.002

Cited by 33 publications

(36 citation statements)

References 32 publications

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“…2C, D), indicating that some E. coli background proteins may be copurified with polyester particles. However, these hostcell background proteins were not immunogenic and did not induce detectable immune responses in mice (38).…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies have shown that polyester particles could be genetically engineered to display antigens of interest (29,30,37). This particle-based vaccine delivery system had been shown to enhance antigen-specific immune responses (25,38). In contrast to live-attenuated vaccines, subunit vaccines are safe but often have low immunogenicity, thereby compromising their protective efficacy (5,6).…”

Section: Discussionmentioning

confidence: 99%

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Innovative antigen carrier system for the development of tuberculosis vaccines

et al. 2019

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A major obstacle to tuberculosis (TB)‐subunit–vaccine development has been the induction of inadequate levels of protective immunity due to the limited breadth of antigen in vaccine preparations. In this study, immunogenic mycobacterial fusion peptides Ag85B‐TB10.4 and Ag85B‐TB10.4‐Rv2660c were covalently displayed on the surface of self‐assembled polyester particles. This study investigated whether polyester particles displaying mycobacterial antigens could provide augmented immunogenicity (i.e., offer an innovative vaccine formulation) when compared with free soluble antigens. Herein, polyester particle–based particulate vaccines were produced in an endotoxin‐free Escherichia coli strain and emulsified with the adjuvant dimethyl dioctadecyl ammonium bromide. C57BL/6 mice were used to study the immunogenicity of formulated particulate vaccines. The result of humoral immunity showed the antibodies only interacted with target antigens and not with PhaC and the background proteins of the production host. The analysis of T helper 1 cellular immunity indicated that a relatively strong production of cellular immunity biomarkers, IFN‐γ and IL‐17A cytokines, was induced by particulate vaccines when compared with the respective soluble controls. This study demonstrated that polyester particles have the potential to perform as a mycobacterial antigen–delivery agent to induce augmented antigen‐specific immune responses in contrast to free soluble vaccines.—Chen, S., Sandford, S., Kirman, J. R., Rehm, B. H. A. Innovative antigen carrier system for the development of tuberculosis vaccines. FASEB J. 33, 7505–7518 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Innovative antigen carrier system for the development of tuberculosis vaccines

et al. 2019

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“…3 and 4, Table 2). PHB beads as antigen carrier isolated from recombinant E. coli were recently demonstrated to induce only antigen specific responses, while potentially co-purifying E. coli proteins did not induce a detectable responses [19]. As the surface charge of particulate vaccine might impact cellular uptake and antigen processing, we assessed the Zeta potential of isolated PHB beads which resulted in anegative charge at physiological pH with an increased negative Zeta potential for the PsaA-PHB beads (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…PHB beads were bioengineered to display antigens from intracellular pathogens like Mycobacterium tuberculosis and Hepatitis C virus. These particulate vaccine candidates elicited both Th1 and Th2 antigen specific immune responses resulting in protective immunity [8, 18, 19]. In this study it was conceived to engineer PHB beads displaying PsaA as possible antigen delivery system to develop a particulate vaccine against the extracellular pathogen S. pneumoniae .…”

Section: Introductionmentioning

confidence: 99%

Self-assembled particulate PsaA as vaccine against Streptococcus pneumoniae infection

González-Miró

Rodríguez-Noda

Fariñas-Medina

et al. 2017

Heliyon

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Streptococcus pneumoniae is a human pathogen responsible for the majority of childhood pneumonia and media otitis cases worldwide. The diversity of its capsular polysaccharides (CPS) results in more than 91 serotypes of which at least 23 are virulent. Various CPS conjugated to immunogenic carrier proteins are currently licensed and provide protection against the infection caused by the respective serotypes but not against new and emerging virulent serotypes. In this study, we considered the conserved protein antigen PsaA, the pneumococcal surface adhesin A, in order to overcome the limitations of CPS antigens. The PsaA was translationally fused to a polyhydroxybutyrate (PHB) synthase which mediated production of PsaA displayed on PHB inclusions in recombinant Escherichia coli. This suggested that the PsaA fusion to the PHB synthase did not interfere with PHB synthase activity and its ability to mediate formation of nano-sized inclusions composed of a PHB core surrounded by the PHB synthase fused to PsaA. Isolated PHB beads showed a negative surface charge. Transmission electron microscopy analysis suggested that the PsaA fusion to the PHB synthase reduced the size of PHB beads from about 500 nm to 100 nm. The integrity and antigenicity of the fusion protein attached to isolated PHB beads was confirmed by SDS-PAGE, tryptic peptide fingerprinting analysis using MALDI-TOF-MS/MS and immunoblotting using a monoclonal anti-PsaA antibody. Mice immunized with PsaA displaying PHB beads produced high and specific IgG levels dominated by IgG1 isotype. While IgG1 titer were similar between soluble and insoluble PsaA, the IgG2 titers were strongly increased upon vaccination with insoluble PsaA i.e. PsaA displayed on PHB beads. Particulate PsaA-PHB beads elicited IgG antibodies recognizing PsaA in whole cell lysates of seven different serotypes of S. pneumoniae. This study suggested that PHB beads are suitable carriers for PsaA in order to induce a significant and specific Th-2-type immune response.

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“…Of significant relevance is the implementation of PHAs in the biomedical discipline, especially supported by the recent FDA approval for P(4HB) to be used as suture material (Tepha Inc., MA, USA). The utility of PHAs in this field arises from their biocompatibility characteristics and has found its application in a variety of processes such as drug delivery, development of medical devices and construction of tissue engineering scaffolds (Misra et al ., ; Wu et al ., ; Wang et al ., ; Xiong et al ., ; Brigham and Sinskey, ; Martinez‐Donato et al ., ; Rubio Reyes et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Polyhydroxyalkanoate‐associated phasins as phylogenetically heterogeneous, multipurpose proteins

Maestro

Sanz

2017

Microbial Biotechnology

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SummaryPolyhydroxyalkanoates (PHAs) are natural polyesters of increasing biotechnological importance that are synthesized by many prokaryotic organisms as carbon and energy storage compounds in limiting growth conditions. PHAs accumulate intracellularly in form of inclusion bodies that are covered with a proteinaceous surface layer (granule‐associated proteins or GAPs) conforming a network‐like surface of structural, metabolic and regulatory polypeptides, and configuring the PHA granules as complex and well‐organized subcellular structures that have been designated as ‘carbonosomes’. GAPs include several enzymes related to PHA metabolism (synthases, depolymerases and hydroxylases) together with the so‐called phasins, an heterogeneous group of small‐size proteins that cover most of the PHA granule and that are devoid of catalytic functions but nevertheless play an essential role in granule structure and PHA metabolism. Structurally, phasins are amphiphilic proteins that shield the hydrophobic polymer from the cytoplasm. Here, we summarize the characteristics of the different phasins identified so far from PHA producer organisms and highlight the diverse opportunities that they offer in the Biotechnology field.

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Immunogencity of antigens from Mycobacterium tuberculosis self-assembled as particulate vaccines

Cited by 33 publications

References 32 publications

Innovative antigen carrier system for the development of tuberculosis vaccines

Innovative antigen carrier system for the development of tuberculosis vaccines

Self-assembled particulate PsaA as vaccine against Streptococcus pneumoniae infection

Polyhydroxyalkanoate‐associated phasins as phylogenetically heterogeneous, multipurpose proteins

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