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J Immunol 2002 Sep 15;169(6):3422-8
 

Inhibition of adjuvant arthritis by a DNA vaccine encoding human heat shock protein 60.

Quintana FJ, Carmi P, Mor F, Cohen IR

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

[Medline record in process]
 

Adjuvant arthritis (AA) is an autoimmune disease inducible in rats involving T cell reactivity to the mycobacterial 65-kDa heat shock protein (HSP65). HSP65-specific T cells cross-reactive with the mammalian 60-kDa heat shock protein (HSP60) are thought to participate in the modulation of AA. In this work we studied the effects on AA of DNA vaccination using constructs coding for HSP65 (pHSP65) or human HSP60 (pHSP60). We found that both constructs could inhibit AA, but that pHSP60 was more effective than pHSP65. The immune effects associated with specific DNA-induced suppression of AA were complex and included enhanced T cell proliferation to a variety of disease-associated Ags. Effective vaccination with HSP60 or HSP65 DNA led paradoxically to up-regulation of IFN-gamma secretion to HSP60 and, concomitantly, to down-regulation of IFN-gamma secretion to the P180-188 epitope of HSP65. There were also variable changes in the profiles of IL-10 secretion to different Ags. However, vaccination with pHSP60 or pHSP65 enhanced the production of TGFbeta1 to both HSP60 and HSP65 epitopes. Our results support a regulatory role for HSP60 autoreactivity in AA and demonstrate that this control mechanism can be activated by DNA vaccination with both HSP60 or HSP65.

PMID: 12218165, UI: 22206887

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J Immunol 2002 Sep 15;169(6):3407-12
 

TCR Rearrangement in Lymphocytes Infiltrating Melanoma Metastases After Administration of Autologous Dinitrophenyl-Modified Vaccine.

Manne J, Mastrangelo MJ, Sato T, Berd D

Department of Medicine, Division of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107.

[Medline record in process]
 

Administration of a vaccine consisting of autologous melanoma cells modified with a hapten, dinitrophenyl (DNP), induces T cell infiltration of metastatic sites. We have reported an analysis of these infiltrating T cells, indicating that certain TCR-Vbeta gene segments are greatly overexpressed. In this study, we investigate the rearrangement of the TCR-Vbeta as well as the junctional diversity in T cells infiltrating melanoma metastases following treatment with DNP vaccine. In 19 of 26 control specimens, V-D-J length analysis showed the expected polyclonal patterns. In contrast, postvaccine tumors from 9 of 10 patients showed dominant peaks of V-D-J junction size in one or more Vbeta families. Dominant peaks were seen most frequently in six Vbeta families (Vbeta7, 12, 13, 14, 16, and 23) and were never seen in seven others. Further analysis of the oligoclonal Vbeta products showed dominant peaks in the J region as well. Of particular interest was the finding that Vbeta and Jbeta peaks were similar in inflamed metastases obtained at different times or from different sites from the same patient. Although 6 of 10 patients expressed HLA-A1, there was no common pattern of TCR rearrangements among them. Finally, the amplified PCR products from seven of these specimens were cloned and sequenced and the amino acid sequence of the complementarity-determining region 3 was deduced. In six of seven specimens, the same complementarity-determining region 3 sequence was repeated in at least two clones and in five of seven in at least three clones. Our study indicates that DNP vaccine induces the expansion of particular T cell clones that may be agents of its antitumor effects.

PMID: 12218163, UI: 22206885

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J Immunol 2002 Sep 15;169(6):3208-16
 

Vaccination with recombinant alphavirus or immune-stimulating complex antigen against respiratory syncytial virus.

Chen M, Hu KF, Rozell B, Orvell C, Morein B, Liljestrom P

Microbiology and Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden. Margaret.Chen@mtc.ki.se

[Medline record in process]
 

Respiratory syncytial virus (RSV) causes severe respiratory diseases in infants and young children. Inappropriate immunity to the virus can lead to disease enhancement upon subsequent infection. In this study, we have characterized the antiviral immunity elicited by the recombinant Semliki Forest virus (SFV) encoding the RSV fusion (F) and attachment (G) protein, and compared with that induced by the immune-stimulating complex (ISCOM)-incorporated FG proteins. Antiviral immunity against RSV elicited nasally or parentally by either of the immunogen having divergent profiles could reduce lung RSV titers upon challenge. However, resistance to RSV without disease enhancement was only observed in those vaccinated with SFV recombinants via nasal route. Presence of postvaccination pulmonary IFN-gamma response to the H-2K(d)-restricted T cell epitope (F(85-93); KYKNAVTEL) was found to be associated with absence of enhanced pulmonary disease and goblet cell hyperplasia as well as reduced Th2-cytokine expression. This result demonstrates that the SFV recombinants can result in enhanced clearance of RSV without enhancing the RSV-associated disease, and underlines the importance in priming pulmonary MHC class I-restricted T cells when RSV FG-based vaccines are used.

PMID: 12218139, UI: 22206861

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J Immunol 2002 Aug 15;169(4):2172-9
 

Inhibition of EBV-induced lymphoproliferation by CD4(+) T cells specific for an MHC class II promiscuous epitope.

Omiya R, Buteau C, Kobayashi H, Paya CV, Celis E

Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.

Posttransplant lymphoproliferative disorder (PTLD) and B cell lymphomas induced by EBV continue to be a major life-threatening complication in transplant patients. The establishment and enhancement of T cell immunity to EBV before transplantation and immunosuppressive therapy could help diminish these complications, but the lack of an effective vaccine has limited this prophylactic approach. We describe here the identification of a peptide epitope from the EBV EBNA2 Ag that is capable of inducing in vitro CD4(+) T cell responses that inhibit the EBV-mediated B lymphocyte proliferation associated with PTLD. Most significantly, T cell responses to the EBNA2 epitope were found to be restricted by numerous MHC class II alleles (DR1, DR7, DR16, DR52, DQ2, and DQ7), indicating that this peptide is highly promiscuous and would be recognized by a large proportion (>50%) of the general population. These results are relevant for the design of a simple, inexpensive and widely applicable peptide-based vaccine to prevent PTLD in solid organ transplant patients.

PMID: 12165547, UI: 22155340

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MMWR Morb Mortal Wkly Rep 2002 Jul 26;51(29):646-7
 

National laboratory inventory as part of global poliovirus containment--United States, June 2002.

Since the initiation of the global poliomyelitis initiative in 1988 through 2001, the number of countries where polio is endemic decreased from 125 to 10, and the number of reported polio cases decreased >99%, from an estimated 350,000 to <1,000. The Global Commission for the Certification of the Eradication of Poliomyelitis, convened by the World Health Organization, will declare the world polio-free when all regions have documented the absence of wild poliovirus transmission for at least 3 consecutive years and when laboratories with wild poliovirus materials have implemented appropriate containment conditions.

PMID: 12186224, UI: 22173525

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