Pathogen recognition and development of particulate vaccines: Does size matter?

Xiang, Sue D.; Scholzen, Anja; Minigo, Gabriela; David, Cassandra T.; Apostolopoulos, Vasso; Mottram, Patricia L.; Plebanski, Magdalena

doi:10.1016/j.ymeth.2006.05.016

Cited by 548 publications

(396 citation statements)

References 155 publications

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Section: Introductionmentioning

confidence: 99%

“…In addition, compared with vaccines based on recombinant proteins and an adjuvant, pathogens are often taken up by different mechanisms by the cells of the immune system [1]. The different uptake mechanisms could lead to different intracellular processing of Ag, giving rise to different epitopes [1]. Furthermore, live pathogens express a wide range of specific lipids and proteins that bind a variety of pattern-recognition receptors on phagocytes and induce signaling through these receptors, whereas recent evidence suggests subunit vaccines more specifically tend to target DC through activation of toll-like receptors [2].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Difference in TB10.4 T‐cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

et al. 2010

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Most novel vaccines against infectious diseases are based on recombinant Ag; however, only few studies have compared Ag-specific immune responses induced by natural infection with that induced by the same Ag in a recombinant form. Here, we studied the epitope recognition pattern of the tuberculosis vaccine Ag, TB10.4, in a recombinant form, or when expressed by the pathogen Mycobacterium tuberculosis (M.tb), or by the current anti-tuberculosis vaccine, Mycobacterium bovis BCG. We showed that BCG and M.tb induced a similar CD4 1 T-cell specific TB10.4 epitope-pattern, which differed completely from that induced by recombinant TB10.4. This difference was not due to post-translational modifications of TB10.4 or because TB10.4 is secreted from BCG and M.tb as a complex with Rv0287. In addition, BCG and TB10.4/CAF01 were both taken up by DC and macrophages in vivo, and in vitro uptake experiments revealed that both TB10.4 and BCG were transported to Lamp 1 -compartments. BCG and TB10.4 however, were directed to different types of Lamp 1 -compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely different recognition of the same protein.Key words: Epitopes . Intracellular localization . Subdominant . T cells . Vaccine uptake IntroductionThe size, shape and nature of a synthetic recombinant vaccine and its target pathogen differ significantly. For instance, bacteria are typically in the range of 0.5-10 mm in diameter, which exceed the size of most viruses by 10 to 100-fold, and protein based adjuvanted vaccines are even smaller. In addition, compared with vaccines based on recombinant proteins and an adjuvant, pathogens are often taken up by different mechanisms by the cells of the immune system [1]. The different uptake mechanisms could lead to different intracellular processing of Ag, giving rise to different epitopes [1]. Furthermore, live pathogens express a wide range of specific lipids 1342and proteins that bind a variety of pattern-recognition receptors on phagocytes and induce signaling through these receptors, whereas recent evidence suggests subunit vaccines more specifically tend to target DC through activation of toll-like receptors [2]. These differences are likely to lead to different responses with regard to the priming of the early immune response [3]. For instance, the main host cell of the intracellular pathogen Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis in humans, is thought to be macrophages [4]; however, although mycobacteria are mainly taken up by macrophages, mycobacteria can infect a wide range of cells including neutrophils, epithelial cells and other cell types [5,6]. On the other hand, viral vaccine vectors have been shown to be ingested largely by immature DC [1], and soluble Ag formulated in cationic adjuvants such as CAF01 or IC31 are also believed to target DC [7,8]. Different types of APC have different mechanisms of Ag uptake, different pH levels in lysosomal co...

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Difference in TB10.4 T‐cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

et al. 2010

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“…Large and insoluble particulate antigens are phagocytosed very efficiently and produce strong responses by themselves. [7][8][9] This is the case for microorganisms such as bacteria and viruses. [10,11] Conversely, small and soluble antigens, such as proteins and peptides, are poorly internalized and thus weakly immunogenic; therefore, an adjuvant is needed to intensify the immune response.…”

Section: Introductionmentioning

confidence: 99%

Carbon nanotube-protein carriers enhance size-dependent self-adjuvant antibody response to haptens

Parra

Abad‐Somovilla

Mercader

et al. 2013

Journal of Controlled Release

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Carbon nanotubes (CNTs) are nanomaterials with interesting emerging applications. Their 25 properties makes CNTs excellent candidates for use as new nanovehicles in drug delivery, immunization and diagnostics. In the current study, we assessed the immune-response-amplifying properties of CNTs to haptens by using azoxystrobin, the first developed strobilurin fungicide, as a model analyte. An azoxystrobin derivative bearing a carboxylated spacer arm (hapten AZc6) was covalently coupled to bovine serum albumin (BSA), and the resulting BSA-AZc6 conjugate was 30 covalently linked to four functionalized CNTs of different shapes and sizes, varying in diameter and length. These four types of CNT-based constructs were obtained using efficient, fast, and easy functionalization procedures based on microwave-assisted chemistry. New Zealand rabbits and BALB/c mice were immunized with BSA-AZc6 alone and with the four CNT-BSA-AZc6 constructs, both with and without Freund's adjuvant. The IgG-type antibody responses were assessed 35 in terms of the titer and affinity, paying special attention to the relationship between the immune response and the size and shape of the employed CNTs. Immunization with CNT-BSA-AZc6 resulted in enhanced titers and excellent affinities for azoxystrobin. More important, remarkable IgG responses were obtained even in the absence of an adjuvant, thus proving the self-adjuvanting capability of CNTs. Immunogens were able to produce strong anti-azoxystrobin immune responses 40 in rabbits even when administered at a BSA-AZc6 conjugate dose as low as 0.05 g. The short and thick CNT-BSA-AZc6 construct produced the best antibody response under all tested conditions.

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“…In recent years, nanotechnology has been widely applied to the study of new adjuvant formulations and vaccine delivery systems [1,29,30]. The ability of vaccines (or their delivery systems) to self-assemble in nanoscale was found to be important for inducing immune responses.…”

Section: Resultsmentioning

confidence: 99%

pH-triggered peptide self-assembly into fibrils: a potential peptide-based subunit vaccine delivery platform

Skwarczynski¹,

Kowapradit²,

Ziora³

et al. 2013

Bio Chem Comp

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Background: Peptide-based subunit vaccines require strong adjuvants (immunostimulant) for therapeutic potency. There is strong demand for the discovery of new safe adjuvants and vaccine delivery systems that can be produced in a highly controlled manner. The pH dependent self-assembly of isopeptide derivatives into fibrils has been reported. Appropriately designed fibrils may have adjuvanting potency. Methods: Isopeptides conjugated to B-cell peptide epitopes (antigens) were synthesized. Properties of the resultant conjugates and their ability to undergo O-N intramolecular acyl migration reaction were analysed by HPLC, circular dichroism, and transmission electron microscopy. Results: The conjugates were converted to "parent" peptides via the pH-triggered O-N acyl migration reaction. The parent peptides aggregated into fibrils. The differences in conjugates composition resulted in different fibril morphology. Aggregation of produced peptides induced desired secondary conformation of antigens (peptide epitopes). Conclusions:The isopeptide approach presented herein may serve as a new self-adjuvanting delivery system for peptide-based vaccines. Such vaccines could be stable when stored in a non-aggregative form, and then converted on demand to the active form in pH-controlled manner. The use of a vaccine that is solely composed of endogenous components may reduce vaccine-associated side effects.

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Pathogen recognition and development of particulate vaccines: Does size matter?

Cited by 548 publications

References 155 publications

Difference in TB10.4 T‐cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

Difference in TB10.4 T‐cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

Carbon nanotube-protein carriers enhance size-dependent self-adjuvant antibody response to haptens

pH-triggered peptide self-assembly into fibrils: a potential peptide-based subunit vaccine delivery platform

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