Vaccine Weekly

Research on immunization discussed by A.V. Misharin and co-researchers

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"However, unlike their poor response to TSHR-DNA vaccination, BALB/c mice vaccinated with thyroid peroxidase (TPO)-cDNA readily develop antibodies to TPO. We hypothesized that insight into these conundrums would be provided by the following differences in central tolerance: (i) between two mouse strains (C57BL/6 versus BALB/c) for the TSHR; and (ii) between two thyroid autoantigens (TPO and the TSHR) in one mouse strain (BALB/c). We studied autoantigen expression using real-time polymerase chain reaction to quantify mRNA transcripts for the TSHR, TPO, and thyroglobulin (Tg) in thymic tissue (as well as in thyroid) of young mice. Our hypothesis was not confirmed. Intrathymic TSHR transcript expression was similar in BALB/c and C57BL/6 mice. Moreover, thymic mRNA transcripts for TSHR and TPO were comparable. Unlike the 10-fold differences for the autoantigens in thyroid tissue (Tg greater than TPO which, in turn was greater than the TSHR), intrathymic transcripts for TPO and the TSHR were similar, both being slightly lower than the level for Tg. Central tolerance, assessed by measuring intrathymic transcripts of thyroid autoantigens, does not explain the different outcome of TSHR-DNA vaccination in BALB/c and C57BL/6 mice, or even susceptibility versus resistance to hyperthyroidism induced by TSHR-adenovirus. Instead, differences in MHC and TSHR T-cell epitopes likely contribute to TSHR antibody development (or not) following DNA plasmid immunization. The greater immunogenicity of TPO versus TSHR probably relates to the greater number of nonhomologous amino acids in the human and mouse TPO ectodomains (78 amino acids) than in the human and mouse TSHR ectodomains (58 amino acids)," wrote A.V. Misharin and colleagues.

The researchers concluded: "Overall, the autoantigens themselves, not central tolerance, control DNA plasmid induced immunity to TPO and the TSHR."

Misharin and colleagues published their study in Thyroid (Thyroid Antigens, Not Central Tolerance, Control Responses to Immunization in BALB/c Versus C57BL/6 Mice. Thyroid, 2009;19(5):503-509).

For additional information, contact A.V. Misharin, Cedars Sinai Med Center, Autoimmune Diseases Unit, 8700 Beverly Blvd., Suite B-131, Los Angeles, CA 90048, USA.

Publisher contact information for the journal Thyroid is: Mary Ann Liebert Inc., 140 Huguenot Street, 3RD FL, New Rochelle, NY 10801, USA.

Keywords: United States, Los Angeles, DNA Research, DNA Vaccines, Diagnosis, Diagnostics, Drugs, Enzyme Research, Immunization, Medical Device, Peroxidase, Pharmaceuticals, Polymerase, Therapy, Thyroglobulin, Thyrotropin, Treatment, Vaccination.

This article was prepared by Vaccine Weekly editors from staff and other reports. Copyright 2009, Vaccine Weekly via NewsRx.com.