Michael N. Oxman

Varicella-Zoster Virus–Specific Immune Responses in Elderly Recipients of a Herpes Zoster Vaccine

BACKGROUNDnA double-blind, placebo-controlled trial that involved 38,546 subjects > or =60 years old demonstrated efficacy of a high-potency live-attenuated Oka/Merck varicella-zoster virus (VZV) vaccine. The trial included an immunology substudy to determine the relationship of VZV-specific immune responses to vaccination and clinical outcome.nnnMETHODSnThe immunology substudy enrolled 1395 subjects at 2 sites where blood samples obtained prior to vaccination, at 6 weeks after vaccination, and at 1, 2, and 3 years thereafter were tested for VZV-specific cell-mediated immunity (VZV-CMI) by gamma-interferon ELISPOT and responder cell frequency assays and for VZV antibody by glycoprotein ELISA.nnnRESULTSnVZV-CMI and VZV antibodies were significantly increased in vaccine recipients at 6 weeks after vaccination. The vaccine-induced increases in VZV-CMI persisted during the 3 years of follow-up, although their magnitude decreased over time. The magnitude of these VZV-specific immune responses was greater in subjects 60-69 years old than in subjects > or =70 years old.nnnCONCLUSIONSnThe zoster vaccine induced a significant increase in VZV-CMI and VZV antibody. The magnitude and duration of the boost in VZV-CMI in vaccine recipients and the relationship of this boost to age paralleled the clinical effects of the vaccine observed during the efficacy trial. These findings support the hypothesis that boosting VZV-CMI protects older adults against herpes zoster and postherpetic neuralgia.

Effect of interferon on exogenous, endogenous, and chronic murine leukemia virus infection.

Abstract The effect of purified mouse interferon on the replication of AKR mouse leukemia virus (MLV) in a clonal line of AKR cells was studied, with emphasis on comparing the effect of interferon on the replication of exogenous virus, activation of endogenous virus by IdUrd, and production of virus by chronically infected cells. It was found that interferon inhibited replication of virus in all three systems. Interferon did not abort exogenous infection or virus induction by IdUrd, but only delayed appearance of infectious virus. Virus production by chronically infected cells also was suppressed in the presence of interferon; however, after removal of interferon, rapid recovery of virus production occurred. Under conditions where interferon treatment inhibited virus yield as measured both by infectious virus and virion-associated reverse transcriptase activity, no significant inhibition of synthesis of virus specific (gs) antigen was observed (as measured by immunofluorescence and radioimmunoassay for p30 protein). These results indicate that unlike its effect on the majority of viruses, interferon does not inhibit MLV by a general inhibition of viral protein synthesis; rather, it appears to inhibit one or more of the later steps in MLV replication which occur after the expression of viral gs antigen. The interferon block of acute exogenous or IdUrd-induced endogenous infection appeared to occur prior to virus assembly, resulting in a marked decrease in the number of free and cell-associated particles. In the chronic infection, however, the interferon treatment only partially prevented assembly and release of virus particles, but these had markedly reduced infectivity.

Studies on the metabolism of adipose tissue. VIII. Alterations produced by biotin deficiency in the rat

Abstract A comparison of the metabolism of glucose in vitro by adipose tissue from normal, biotin-deficient, and biotin-restored rats has been made. Insulin enhances the uptake of glucose by tissue from all three types of animals. In the biotin-deficient animal, 41% of the glucose is converted to lactic acid as compared to 7% in the normal. A corresponding decrease in the net CO 2 production is observed in the biotin-deficient animal signifying a lowered fatty acid synthesis. A single injection of 300 μg. biotin results in a rapid restoration of the metabolic pattern toward the normal.