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November 21, 2011PLoS ONEOpen Access

Design and Analysis of Rhesus Cytomegalovirus IL-10 Mutants as a Model for Novel Vaccines against Human Cytomegalovirus

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Key result

Immunization with inactive RhCMVIL-10 mutants stimulated antibodies against wild-type RhCMVIL-10 that neutralized its biological activity without cross-reacting with rhesus cellular IL-10.

Population

RhCMV-infected rhesus macaques

Design

Preclinical

Authors

NLNaomi J. LogsdonUniversity of Alabama at BirminghamMEMeghan K. EberhardtUniversity of California, DavisCAChristopher E. AllenSupélec

Discussion

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Implication

May support CMVIL-10-specific vaccination strategies; leaves open whether targeted neutralization alters HCMV persistence in vivo.

Structured PICO

P
Population
6 RhCMV-infected rhesus macaques immunized with non-functional RhCMVIL-10 mutants to evaluate neutralizing antibody responses.
I
Intervention
Vaccination with engineered biologically inactive mutants of rhesus cytomegalovirus IL-10 (RhCMVIL-10)
O
Outcome
Stimulation of antibodies against wild-type RhCMVIL-10 that neutralize its biological activity without cross-reacting with rhesus cellular IL-10surrogate

Engineered inactive viral IL-10 mutants can elicit neutralizing antibodies against wild-type viral IL-10 without targeting host cellular IL-10, offering a novel vaccine strategy against cytomegalovirus.

Limitations

  • Small sample size (N=6)
  • Animal model (rhesus macaques) may not perfectly translate to humans
  • One animal did not develop detectable neutralizing antibodies

Cite This Study

Logsdon et al. (2011) studied RhCMV infection (n=6). RhCMVIL-10 mutants (M1 and M2) vs. Pre-immunization baseline was evaluated on Neutralization of WT RhCMVIL-10 biological activity. Immunization with inactive RhCMVIL-10 mutants stimulated antibodies against wild-type RhCMVIL-10 that neutralized its biological activity without cross-reacting with rhesus cellular IL-10.

synapsesocial.com/papers/6ab6281ae6177a6874fb8adfhttps://doi.org/10.1371/journal.pone.0028127
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Interleukin-10 and the Interleukin-10 Receptor2001 · 6,784 citations
  2. 2Murine Cytomegalovirus Infection Down-Regulates MHC Class II Expression on Macrophages by Induction of IL-101999 · 160 citations
  3. 3Crystal structure of human cytomegalovirus IL-10 bound to soluble human IL-10R12002 · 132 citations
  4. 4IL-10 down-regulates costimulatory molecules on<i>Mycobacterium tuberculosis</i>-pulsed macrophages and impairs the lytic activity of CD4 and CD8 CTL in tuberculosis patients2004 · 85 citations
  5. 5Sequences of complete human cytomegalovirus genomes from infected cell cultures and clinical specimens2009 · 124 citations