In vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine.

Background: It was hypothesized that the observed slight immunostimulatory effect of the 23-valent pneumococcal polysaccharide (pneumo-23) vaccine might be due to the presence of low levels of zwitterionic motifs. Therefore, it was hypothesized further that introducing zwitterionic motifs experiment...

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Main Authors: Abdulamir, Ahmed Sahib, Hafidh, Rand Riadh, Abu Bakar, Fatimah
Format: Article
Language:English
English
Published: Elsevier 2010
Online Access:http://psasir.upm.edu.my/id/eprint/15166/
http://psasir.upm.edu.my/id/eprint/15166/1/In%20vitro%20immunogenic%20and%20immunostimulatory%20effects%20of%20zwitterionized%2023.pdf
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author Abdulamir, Ahmed Sahib
Hafidh, Rand Riadh
Abu Bakar, Fatimah
author_facet Abdulamir, Ahmed Sahib
Hafidh, Rand Riadh
Abu Bakar, Fatimah
author_sort Abdulamir, Ahmed Sahib
building UPM Institutional Repository
collection Online Access
description Background: It was hypothesized that the observed slight immunostimulatory effect of the 23-valent pneumococcal polysaccharide (pneumo-23) vaccine might be due to the presence of low levels of zwitterionic motifs. Therefore, it was hypothesized further that introducing zwitterionic motifs experimentally into polysaccharides of pneumo-23 vaccine might render it an effective immunostimulatory agent. Objective: This study was conducted to assess the in vitro immunostimulatory effect of zwitterionized pneumo-23 (Z-P23) vaccine compared with the nonzwitterionized commercial pneumo-23 (C-P23) vaccine. Methods: In vitro proliferation, ELISA-based in vitro cytokine synthesis (interleukin [IL]-2, interferon [IFN]-γ, and IL-10), and immunofluorescence microscopy-based immune cell profiling (CD4+, CD8+, and CD21+ cells) assays were used to evaluate the immunostimulatory effect of Z-P23 on peripheral blood mononuclear cells (PBMC) of immunosuppressed cancer (IC) patients and healthy control subjects in comparison with PBMC exposed to C-P23, concanavalin A (positive control), and phosphate-buffered saline (PBS) (negative control). Results: Z-P23 induced proliferation of PBMC in the IC (81.1%) and control (75.1%) groups significantly higher than that achieved with concanavalin A in the IC group (51.0%; P = 0.01) but not in the control group (89.2%; P = NS). This was also significantly higher than that achieved with C-P23 in the IC (4.8%; P < 0.001) and control (6.2%; P < 0.001) groups. Z-P23 induced IL-2 and IFN-γ synthesis in the IC group (0.61 and 0.45 ng/mL, respectively) significantly more than that with C-P23 (0.4 and 0.45 ng/mL; P = 0.002 and P <0.001), concanavalin A (0.45 and 0.31 ng/mL; P = 0.021 and P = 0.03), and PBS (0.41 and 0.29 ng/mL; P = 0.005 and P = 0.04) but not the control group. Z-P23 induced expansion of CD4+, CD8+, and CD21+ lymphocytes (39.3%, 42.7%, and 8.1%, respectively) in the IC group higher than that with C-P23 (28.3%, 30.1%, and 5.5%; P = 0.01, P = 0.003, and P = NS), concanavalin A (27.2%, 35.8%, and 4.1%; P = 0.02, P = 0.048, and P = 0.035), and PBS (25.6%, 31.9%, and 4.2%; P = 0.018, P = 0.02, and P = 0.045). Conclusion: The in vitro immunostimulatory potential of Z-P23 was clearly observed on PBMC of IC patients as well as, to a lesser extent, healthy control subjects, stimulating the synthesis of core cytokines of T-helper 1, and primarily inducing CD4+ and CD8+T cells.
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spelling upm-151662015-11-02T03:23:01Z http://psasir.upm.edu.my/id/eprint/15166/ In vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine. Abdulamir, Ahmed Sahib Hafidh, Rand Riadh Abu Bakar, Fatimah Background: It was hypothesized that the observed slight immunostimulatory effect of the 23-valent pneumococcal polysaccharide (pneumo-23) vaccine might be due to the presence of low levels of zwitterionic motifs. Therefore, it was hypothesized further that introducing zwitterionic motifs experimentally into polysaccharides of pneumo-23 vaccine might render it an effective immunostimulatory agent. Objective: This study was conducted to assess the in vitro immunostimulatory effect of zwitterionized pneumo-23 (Z-P23) vaccine compared with the nonzwitterionized commercial pneumo-23 (C-P23) vaccine. Methods: In vitro proliferation, ELISA-based in vitro cytokine synthesis (interleukin [IL]-2, interferon [IFN]-γ, and IL-10), and immunofluorescence microscopy-based immune cell profiling (CD4+, CD8+, and CD21+ cells) assays were used to evaluate the immunostimulatory effect of Z-P23 on peripheral blood mononuclear cells (PBMC) of immunosuppressed cancer (IC) patients and healthy control subjects in comparison with PBMC exposed to C-P23, concanavalin A (positive control), and phosphate-buffered saline (PBS) (negative control). Results: Z-P23 induced proliferation of PBMC in the IC (81.1%) and control (75.1%) groups significantly higher than that achieved with concanavalin A in the IC group (51.0%; P = 0.01) but not in the control group (89.2%; P = NS). This was also significantly higher than that achieved with C-P23 in the IC (4.8%; P < 0.001) and control (6.2%; P < 0.001) groups. Z-P23 induced IL-2 and IFN-γ synthesis in the IC group (0.61 and 0.45 ng/mL, respectively) significantly more than that with C-P23 (0.4 and 0.45 ng/mL; P = 0.002 and P <0.001), concanavalin A (0.45 and 0.31 ng/mL; P = 0.021 and P = 0.03), and PBS (0.41 and 0.29 ng/mL; P = 0.005 and P = 0.04) but not the control group. Z-P23 induced expansion of CD4+, CD8+, and CD21+ lymphocytes (39.3%, 42.7%, and 8.1%, respectively) in the IC group higher than that with C-P23 (28.3%, 30.1%, and 5.5%; P = 0.01, P = 0.003, and P = NS), concanavalin A (27.2%, 35.8%, and 4.1%; P = 0.02, P = 0.048, and P = 0.035), and PBS (25.6%, 31.9%, and 4.2%; P = 0.018, P = 0.02, and P = 0.045). Conclusion: The in vitro immunostimulatory potential of Z-P23 was clearly observed on PBMC of IC patients as well as, to a lesser extent, healthy control subjects, stimulating the synthesis of core cytokines of T-helper 1, and primarily inducing CD4+ and CD8+T cells. Elsevier 2010 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/15166/1/In%20vitro%20immunogenic%20and%20immunostimulatory%20effects%20of%20zwitterionized%2023.pdf Abdulamir, Ahmed Sahib and Hafidh, Rand Riadh and Abu Bakar, Fatimah (2010) In vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine. Current Therapeutic Research-Clinical and Experimental, 71 (1 / February). pp. 60-77. ISSN 0011-393X http://dx.doi.org/10.1016/j.curtheres.2010.02.004 English
spellingShingle Abdulamir, Ahmed Sahib
Hafidh, Rand Riadh
Abu Bakar, Fatimah
In vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine.
title In vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine.
title_full In vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine.
title_fullStr In vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine.
title_full_unstemmed In vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine.
title_short In vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine.
title_sort in vitro immunogenic and immunostimulatory effects of zwitterionized 23-valent pneumococcal polysaccharide vaccine compared with nonzwitterionized vaccine.
url http://psasir.upm.edu.my/id/eprint/15166/
http://psasir.upm.edu.my/id/eprint/15166/
http://psasir.upm.edu.my/id/eprint/15166/1/In%20vitro%20immunogenic%20and%20immunostimulatory%20effects%20of%20zwitterionized%2023.pdf