Adjuvanticity of a Recombinant Calreticulin Fragment in Assisting Anti-β-Glucan IgG Responses in T Cell-Deficient Mice

Wei-ji, LI; Long, Kai; Dong, Han; Gao, Xiao‐Ming

doi:10.1128/cvi.00689-12

Cited by 12 publications

(9 citation statements)

References 43 publications

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“…Moreover, the potent adjuvanticity of the rCRT polypeptides is also quite phenomenal. For instance, rCRT/39-272 (mostly in oligomeric forms) is able to assist the production of IgG Abs against fused target proteins or conjugated polysaccharides in healthy mice or T-cell-deficient nude mice [17,22]. Dimerization/oligomerization of soluble CRT was also observed by previous investigators.…”

Section: Discussionmentioning

confidence: 61%

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Self-Oligomerization Is Essential for Enhanced Immunological Activities of Soluble Recombinant Calreticulin

et al. 2013

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We have recently reported that calreticulin (CRT), a luminal resident protein, can be found in the sera of patients with rheumatoid arthritis and also that recombinant CRT (rCRT) exhibits extraordinarily strong immunological activities. We herein further demonstrate that rCRT fragments 18–412 (rCRT/18-412), rCRT/39-272, rCRT/120-308 and rCRT/120-250 can self-oligomerize in solution and are 50–100 fold more potent than native CRT (nCRT, isolated from mouse livers) in activating macrophages in vitro. We narrowed down the active site of CRT to residues 150–230, the activity of which also depends on dimerization. By contrast, rCRT/18-197 is almost completely inactive. When rCRT/18-412 is fractionated into oligomers and monomers by gel filtration, the oligomers maintain most of their immunological activities in terms of activating macrophages in vitro and inducing specific antibodies in vivo, while the monomers were much less active by comparison. Additionally, rCRT/18-412 oligomers are much better than monomers in binding to, and uptake by, macrophages. Inhibition of macrophage endocytosis partially blocks the stimulatory effect of rCRT/18-412. We conclude that the immunologically active site of CRT maps between residues 198–230 and that soluble CRT could acquire potent immuno-pathological activities in microenvironments favoring its oligomerization.

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Section: Discussionmentioning

confidence: 61%

“…16). Most, if not all, other protein antigens are unable to induce IgG production in T-cell-deficient nude mice, yet rCRT/39-272 and rCRT/18-412 could do so relatively efficiently [16,22]. Moreover, the potent adjuvanticity of the rCRT polypeptides is also quite phenomenal.…”

Section: Discussionmentioning

confidence: 99%

Self-Oligomerization Is Essential for Enhanced Immunological Activities of Soluble Recombinant Calreticulin

et al. 2013

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“…This mechanism that allows the recognition and responses to conserved structural components, particularly β-glucans, has evolved in mammals as a defense against fungal pathogens [ 10 ]. Research has shown that LAM with β-glucan from a non-fungal source may contribute to possible vaccination against different fungi ( Table 3 ), while more recently the use of proteins, derived from different bacteria, were conjugated to the polysaccharide LAM model and tested in mice for their ability to induce antibodies against the carbohydrate antigen [ 93 , 97 ].…”

Section: Lam As Vaccinementioning

confidence: 99%

Overview of β-Glucans from Laminaria spp.: Immunomodulation Properties and Applications on Biologic Models

Mendonca

Capoci

Tobaldini-Valério

et al. 2017

IJMS

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Glucans are a group of glucose polymers that are found in bacteria, algae, fungi, and plants. While their properties are well known, their biochemical and solubility characteristics vary considerably, and glucans obtained from different sources can have different applications. Research has described the bioactivity of β-glucans extracted from the algae of the Laminaria genus, including in vivo and in vitro studies assessing pro- and anti-inflammatory cytokines, vaccine production, inhibition of cell proliferation, and anti- and pro-oxidant activity. Thus, the objective of this article was to review the potential application of β-glucans from Laminaria spp. in terms of their immunomodulatory properties, microorganism host interaction, anti-cancer activity and vaccine development.

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“…This characteristic was exploited as an effective carrier or adjuvant for β-glucans in assisting the production of glycotope-specific IgG antibodies in healthy as well as in immunocompromised mice. Laminarin conjugated with a peptide from Calreticulin (LAM-CRT) induced proliferation of B lymphocytes and production of specific laminarin and β-1,3-glucans IgG1 antibodies, even in athymic (T-cell-deficient) nude mice [97]. Vaccination with LAM-CRT protected mice against systemic C. albicans challenge with a survival rate around 60%.…”

Section: Cell Wall Component Vaccinesmentioning

confidence: 99%

Vaccination Against Fungal Diseases: Lessons from Candida albicans

Sampaio

Pais

2017

Immunogenetics of Fungal Diseases

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The advances in medicine have achieved great benefits by improving or even eliminating various debilitating diseases or malignancies, expanding life expectancy. However, it has also originated the development of a compromised population susceptible to opportunistic diseases. A global major concern is the emergence and spread of life-threatening invasive infections in immunocompromised patients, in which the opportunistic fungal infections have greatly increased in the last decades. The high mortality rates associated with these infections, which remain as high as 40%, are due to the limited therapeutic options and the emergence of drug resistant fungi, but also due to the lack of efficient early diagnosis. Consequently, these facts led to the opinion that new approaches are needed to improve the outcome of these patients, such as immunopreventive strategies that could even be combined with standard antifungal treatment. In view of the proven effectiveness of various antibacterial and antiviral vaccines in preventing the respective diseases, several works have been developed to induce protective immunity against fungal infections as well. The better understanding of how the immune system works against fungal pathogens has made possible to explore immunomodulatory strategies that can protect both immunocompetent and immunocompromised hosts and generate memory. Recently, two fungal vaccines against Candida have advanced through clinical trials. However, there are still many challenges in the development of an efficient vaccine against invasive fungal infections. We will provide an update on the progress made in immunization against fungal infections, reviewing host-fungi interactions, antigens and adjuvants exploited in vaccine strategies, and discuss concerns that need to be overcome to further advance in the area of fungal vaccines.

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Adjuvanticity of a Recombinant Calreticulin Fragment in Assisting Anti-β-Glucan IgG Responses in T Cell-Deficient Mice

Cited by 12 publications

References 43 publications

Self-Oligomerization Is Essential for Enhanced Immunological Activities of Soluble Recombinant Calreticulin

Self-Oligomerization Is Essential for Enhanced Immunological Activities of Soluble Recombinant Calreticulin

Overview of β-Glucans from Laminaria spp.: Immunomodulation Properties and Applications on Biologic Models

Vaccination Against Fungal Diseases: Lessons from Candida albicans

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