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  • Design and analysis of rhesus cytomegalovirus IL-10 mutants as a model for novel vaccines against human cytomegalovirus.

Design and analysis of rhesus cytomegalovirus IL-10 mutants as a model for novel vaccines against human cytomegalovirus.

PloS one (2011-12-02)
Naomi J Logsdon, Meghan K Eberhardt, Christopher E Allen, Peter A Barry, Mark R Walter
ABSTRACT

Human cytomegalovirus (HCMV) expresses a viral ortholog (CMVIL-10) of human cellular interleukin-10 (cIL-10). Despite only ∼26% amino acid sequence identity, CMVIL-10 exhibits comparable immunosuppressive activity with cIL-10, attenuates HCMV antiviral immune responses, and contributes to lifelong persistence within infected hosts. The low sequence identity between CMVIL-10 and cIL-10 suggests vaccination with CMVIL-10 may generate antibodies that specifically neutralize CMVIL-10 biological activity, but not the cellular cytokine, cIL-10. However, immunization with functional CMVIL-10 might be detrimental to the host because of its immunosuppressive properties. Structural biology was used to engineer biologically inactive mutants of CMVIL-10 that would, upon vaccination, elicit a potent immune response to the wild-type viral cytokine. To test the designed proteins, the mutations were incorporated into the rhesus cytomegalovirus (RhCMV) ortholog of CMVIL-10 (RhCMVIL-10) and used to vaccinate RhCMV-infected rhesus macaques. Immunization with the inactive RhCMVIL-10 mutants stimulated antibodies against wild-type RhCMVIL-10 that neutralized its biological activity, but did not cross-react with rhesus cellular IL-10. This study demonstrates an immunization strategy to neutralize RhCMVIL-10 biological activity using non-functional RhCMVIL-10 antigens. The results provide the methodology for targeting CMVIL-10 in vaccine, and therapeutic strategies, to nullify HCMV's ability to (1) skew innate and adaptive immunity, (2) disseminate from the site of primary mucosal infection, and (3) establish a lifelong persistent infection.

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Bovine Serum Albumin, Cohn Fraction V, lyophilized powder, ≥96% (agarose gel electrophoresis)
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Bovine Serum Albumin, lyophilized powder, protease, essentially free, ≥98% (agarose gel electrophoresis)
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250 g
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Bovine Serum Albumin, lyophilized powder, Essentially fatty acid free
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Bovine Serum Albumin, heat shock fraction, pH 5.2, ≥96%
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Bovine Serum Albumin, lyophilized powder, Protease, essentially free, ≥98% (agarose gel electrophoresis)
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250 g
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Bovine Serum Albumin, lyophilized powder, ≥96% (agarose gel electrophoresis)
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250 g
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Bovine Serum Albumin, lyophilized powder, essentially γ-globulin free, ≥98% (agarose gel electrophoresis)
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250 g
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Bovine Serum Albumin, lyophilized powder, essentially fatty acid free, ≥97% (agarose gel electrophoresis), 1X Crystallized
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250 g
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Bovine Serum Albumin, cold ethanol fraction, pH 5.2, ≥96%
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Bovine Serum Albumin, lyophilized powder, essentially IgG free, ≥96% (agarose gel electrophoresis)
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Bovine Serum Albumin, lyophilized powder, ≥96% (agarose gel electrophoresis)
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Bovine Serum Albumin, fatty acid free, low endotoxin, lyophilized powder, BioReagent, suitable for cell culture, ≥96% (agarose gel electrophoresis)
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250 g
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Bovine Serum Albumin, heat shock fraction, microbiologically tested, ≥96% (agarose gel electrophoresis)
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Bovine Serum Albumin, heat shock fraction, pH 7, ≥98%
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250 g
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Bovine Serum Albumin, heat shock fraction, pH 7, ≥98%
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250 g
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$333.00
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Bovine Serum Albumin, lyophilized powder, essentially globulin free, ≥99% (agarose gel electrophoresis)
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Bovine Serum Albumin, lyophilized powder, 1× crystallized, ≥97% (agarose gel electrophoresis)
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250 g
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Bovine Serum Albumin, heat shock fraction, suitable for RIA, pH 5.2, ≥96%
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250 g
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Bovine Serum Albumin, heat shock fraction, lyophilized powder, essentially fatty acid free, ≥98% (agarose gel electrophoresis)
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250 g
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$1,670.00
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Bovine Serum Albumin, heat shock fraction, protease free, suitable for hybridization, pH 7, ≥98%
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250 g
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2.5 kg
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Bovine Serum Albumin, lyophilized powder, low endotoxin, BioReagent, suitable for cell culture, ≥98% (agarose gel electrophoresis)
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250 g
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Bovine Serum Albumin, For use as a marker in SDS-PAGE
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Bovine Serum Albumin, chromatographically purified, New Zealand origin, low endotoxin, suitable for cell culture, pH 7, ≥98%
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Bovine Serum Albumin, dimer mol wt ~132 kDa
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Bovine Serum Albumin, lyophilized powder, BioReagent, suitable for cell culture
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250 g
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Bovine Serum Albumin, heat shock fraction, protease free, fatty acid free, essentially globulin free, pH 7, ≥98%
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250 g
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2.5 kg
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$1,670.00
Sigma-Aldrich
Bovine Serum Albumin, lyophilized powder, essentially fatty acid free, ≥96% (agarose gel electrophoresis)
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250 g
Estimated to ship on March 24, 2025
$333.00
2.5 kg
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$1,670.00
Sigma-Aldrich
Bovine Serum Albumin, lyophilized powder, essentially globulin free, low endotoxin, ≥98% (agarose gel electrophoresis)
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250 g
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2.5 kg
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$1,670.00
Sigma-Aldrich
Bovine Serum Albumin, powder, BioXtra
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250 g
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2.5 kg
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Sigma-Aldrich
Bovine Serum Albumin, lyophilized powder, essentially fatty acid free and essentially globulin free, ≥99% (agarose gel electrophoresis)
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SKUPack SizeAvailabilityPriceQuantity
250 g
Estimated to ship on March 24, 2025
$333.00
2.5 kg
Estimated to ship on March 24, 2025
$1,670.00