Wise Young
01-07-2002, 02:21 AM
• Cochlovius B, Stassar MJ, Schreurs MW, Benner A and Adema GJ (2002). Oral DNA vaccination: antigen uptake and presentation by dendritic cells elicits protective immunity. Immunol Lett. 80 (2): 89-96. Summary: Melanoma differentiation antigens, such as glycoprotein 100 (gp100), have been shown to induce both cellular and humoral immune responses against melanoma in mouse and man. They are therefore considered as potential targets for melanoma immunotherapy. In this study, we have used the attenuated auxotrophic mutant strain SL7207 of Salmonella typhimurium as vehicle for a human gp100 (hgp100) DNA vaccine against melanoma. In vitro studies indicate that Salmonella/pCMV-hgp100 is efficiently scavenged by dendritic cells, resulting in the expression of the hgp100 transcription unit in the DC. In addition, oral administration of Salmonella/pCMV-hgp100 results in the expression of hgp100 RNA and protein by cells exhibiting DC-morphology in mesenteric lymph nodes as soon as 3 days after vaccination. Analysis of the efficacy of the Salmonella/pCMV-hgp100 vaccine in the B16/hgp100 model demonstrated the induction of strong anti-hgp100 CTL responses and protective immunity in 70% of the vaccinated mice, but not in control mice. Based on these data, we consider S. typhimurium as a useful vehicle for the design of recombinant DNA based anti-cancer vaccines. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11750039> Division of Diagnostics and Experimental Therapy, German Cancer Research Centre (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
• Delogu G, Li A, Repique C, Collins F and Morris SL (2002). DNA vaccine combinations expressing either tissue plasminogen activator signal sequence fusion proteins or ubiquitin-conjugated antigens induce sustained protective immunity in a mouse model of pulmonary tuberculosis. Infect Immun. 70 (1): 292-302. Summary: DNA vaccination has emerged as a powerful approach in the search for a more efficacious vaccine against tuberculosis. In this study, we evaluated the effectiveness of immunizing with combinations of 10 different tuberculosis DNA vaccines that expressed mycobacterial proteins fused at the N terminus to eukaryotic intracellular targeting sequences. In one vaccine combination, the genes were fused to the tissue plasminogen activator signal sequence (TPA), while in a second combination the same 10 genes were expressed as ubiquitin (Ub)-conjugated proteins. In ex vivo studies in which the secretion of gamma interferon was measured, cellular immune responses were detected in mice vaccinated with either the TPA DNA vaccine combination or the Ub DNA vaccine combination at 7 and 14 days following a low-dose Mycobacterium tuberculosis challenge. Moreover, mice vaccinated with the TPA combination, the Ub combination, and Mycobacterium bovis BCG were able to limit the growth of tubercle bacilli in the lung and spleen after a virulent tuberculous aerosol challenge. Histopathological analyses also showed that mice immunized with the DNA vaccine combinations had substantially improved postinfection lung pathology relative to the naive controls. Finally, in three different long-term experiments, the survival periods following aerogenic challenge were extended as much as sevenfold for vaccinated mice compared to naive controls. Interestingly, in all three experiments, no significant differences were detected in the mean times to death for mice immunized with the TPA combination or the Ub combination relative to the BCG controls. In conclusion, these studies demonstrate the effectiveness of immunization with DNA vaccine combinations against tuberculosis and suggest that further testing of these plasmid cocktails is warranted. <http://iai.asm.org/cgi/content/full/70/1/292
http://iai.asm.org/cgi/content/abstract/70/1/292
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11748195> Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
• Ishii N, Sugita Y, Liu LJ, Watabe S, Toda S, Xin KQ and Okuda K (2001). Immunologic characterization of HIV-specific DNA vaccine. J Investig Dermatol Symp Proc. 6 (1): 76-80. Summary: We developed a method for applying HIV-1 DNA vaccine topically in mice. Topical application of DNA vaccine to the skin is useful against infections. To find a less expensive and less cumbersome vaccination method, we administered HIV-1 DNA vaccine to the skin of mice after elimination of keratinocytes using a fast-acting adhesive. HIV-1 DNA vaccine induced high levels of both humoral and cell-mediated immune activity against HIV-1 envelope antigen. A high level of HIV-1-specific cytotoxic T lymphocyte response was also observed, and a high level of IFN-gamma and IL-4 production was induced by the improved skin application of DNA vaccine. High levels of both HIV-specific cytotoxic T lymphocyte and delayed type hypersensitivity in topical application were induced by coadministration of the DNA vaccine with IL-12 expression plasmids and granulocyte-macrophage colony-stimulating factor expression plasmids. These immune responses were inhibited by intradermal injection of anti-CD11c or anti-I-A/I-E antibody. Therefore, topical administration of DNA vaccine is an effective route, and may be very useful for the prevention of infectious diseases. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11764291> Leprosy Research Center, National Institute of Infectious Diseases, Higashi-murayama, Tokyo, Japan. norishii@nih.go.jp
• Kraehenbuhl JP (2001). Mucosa-targeted DNA vaccination. Trends Immunol. 22 (12): 646-8. Summary: <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11738975>
• Roche PW, Neupane KD, Failbus SS, Kamath A and Britton WJ (2001). Vaccination with DNA of the Mycobacterium tuberculosis 85B antigen protects mouse foot pad against infection with M. leprae. Int J Lepr Other Mycobact Dis. 69 (2): 93-8. Summary: A DNA vaccine composed of the gene for the common mycobacterial secreted protein antigen 85B was demonstrated to protect the mouse foot pad against infection with Mycobacterium leprae. The protective effect was demonstrated by a 61%-88% reduction in the bacterial number, a protective effect less than that of BCG. The same DNA vaccine has been shown to protect mice against M. tuberculosis infection, and the importance of testing other candidate tuberculosis vaccines for their potential to protect against leprosy is discussed. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11757171> Mycobacterial Research Laboratory, Anandaban Leprosy Hospital, Kathmandu, Nepal. paulwroche@hotmail.com
• Shibui A, Ohmori Y, Suzuki Y, Sasaki M, Nogami S, Sugano S and Watanabe J (2001). Effects of DNA vaccine in murine malaria using a full-length cDNA library. Res Commun Mol Pathol Pharmacol. 109 (3-4): 147-57. Summary: In an attempt to develop a novel malaria vaccine, we constructed a full-length cDNA library from the erythrocytic-stage parasites of Plasmodium berghei ANKA strain using the plasmid vector pCE-FL, which is driven by an EF321 promoter and a CMV-IE enhancer. Here we report the initial trial to screen this library for DNA vaccine candidates against malaria parasite infection in mice. The library of P. berghei was divided into five groups, each representing 2,000 independent clones. Eight female BALB/c mice were injected with these subsets, with an initial injection directly into the spleen, followed by two subsequent intramuscular injections at 1-week intervals. As a control, the plasmid vector without any insert was used. Two weeks after the last injection, 50,000 infected erythrocytes were injected intraperitoneally. Unexpectedly, the survival rate of the vaccinated groups was lower than that of the control (p = 0.053, by Kaplan-Meyer method), suggesting that these DNA vaccines had adverse effects. There was no difference in parasitemia between the two groups. There was no difference between antibody titers before and after immunization in either group. Accelerated deaths in immunized mice occurred from 7 to 10 days after infection, when fur bristling, shivering and convulsions were observed. These observations suggested the possibility that the vaccination had an adverse effect on the cellular immunity that resulted in the development of severe malaria in BALB/c mice, which do not usually develop cerebral malaria. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11758646> Department of Virology, Institute of Medical Science, The University of Tokyo, Japan.
• Stevenson FK, Zhu D and Rice J (2001). New strategies for vaccination and imunomodulation in NHL. Ann Hematol. 80 Suppl 3: B132-4. Summary: Knowledge of the genetic changes which occur in cancer cells is stimulating research aimed towards new therapies. Immunotherapeutic approaches, particularly antibody therapy, are already finding a place in treatment of hematological malignancies. Vaccination will build on experience in the field of infectious diseases, and it should be possible to design vehicles to deliver the expanding range of tumour antigens to the immune system. For DNA vaccines, fusion genes have the potential to activate and direct immune effector pathways. One candidate antigen for B-cell malignancies is the clonal idiotypic immunoglobulin and we have designed a fusion vaccine encoding idiotypic sequence fused to a sequence from a powerful antigen from tetanus toxin. This promotes protective immunity against lymphoma in models, and is now in clinical trial. One challenge is to bring patients into remission without significant damage to immune capacity. Another is to rethink the nature of clinical trials so that more pilot studies of efficacy can be carried out. There is no evidence so far of toxicity due to injection of DNA, but for antigens which are expressed by normal cells, the line between attack on tumour and autoimmunity will have to be carefully drawn. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11757697> Tenovus Laboratory, Southampton University Hospitals Trust, UK. fs@soton.ac.uk
• Delogu G, Li A, Repique C, Collins F and Morris SL (2002). DNA vaccine combinations expressing either tissue plasminogen activator signal sequence fusion proteins or ubiquitin-conjugated antigens induce sustained protective immunity in a mouse model of pulmonary tuberculosis. Infect Immun. 70 (1): 292-302. Summary: DNA vaccination has emerged as a powerful approach in the search for a more efficacious vaccine against tuberculosis. In this study, we evaluated the effectiveness of immunizing with combinations of 10 different tuberculosis DNA vaccines that expressed mycobacterial proteins fused at the N terminus to eukaryotic intracellular targeting sequences. In one vaccine combination, the genes were fused to the tissue plasminogen activator signal sequence (TPA), while in a second combination the same 10 genes were expressed as ubiquitin (Ub)-conjugated proteins. In ex vivo studies in which the secretion of gamma interferon was measured, cellular immune responses were detected in mice vaccinated with either the TPA DNA vaccine combination or the Ub DNA vaccine combination at 7 and 14 days following a low-dose Mycobacterium tuberculosis challenge. Moreover, mice vaccinated with the TPA combination, the Ub combination, and Mycobacterium bovis BCG were able to limit the growth of tubercle bacilli in the lung and spleen after a virulent tuberculous aerosol challenge. Histopathological analyses also showed that mice immunized with the DNA vaccine combinations had substantially improved postinfection lung pathology relative to the naive controls. Finally, in three different long-term experiments, the survival periods following aerogenic challenge were extended as much as sevenfold for vaccinated mice compared to naive controls. Interestingly, in all three experiments, no significant differences were detected in the mean times to death for mice immunized with the TPA combination or the Ub combination relative to the BCG controls. In conclusion, these studies demonstrate the effectiveness of immunization with DNA vaccine combinations against tuberculosis and suggest that further testing of these plasmid cocktails is warranted. <http://iai.asm.org/cgi/content/full/70/1/292
http://iai.asm.org/cgi/content/abstract/70/1/292
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11748195> Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
• Ishii N, Sugita Y, Liu LJ, Watabe S, Toda S, Xin KQ and Okuda K (2001). Immunologic characterization of HIV-specific DNA vaccine. J Investig Dermatol Symp Proc. 6 (1): 76-80. Summary: We developed a method for applying HIV-1 DNA vaccine topically in mice. Topical application of DNA vaccine to the skin is useful against infections. To find a less expensive and less cumbersome vaccination method, we administered HIV-1 DNA vaccine to the skin of mice after elimination of keratinocytes using a fast-acting adhesive. HIV-1 DNA vaccine induced high levels of both humoral and cell-mediated immune activity against HIV-1 envelope antigen. A high level of HIV-1-specific cytotoxic T lymphocyte response was also observed, and a high level of IFN-gamma and IL-4 production was induced by the improved skin application of DNA vaccine. High levels of both HIV-specific cytotoxic T lymphocyte and delayed type hypersensitivity in topical application were induced by coadministration of the DNA vaccine with IL-12 expression plasmids and granulocyte-macrophage colony-stimulating factor expression plasmids. These immune responses were inhibited by intradermal injection of anti-CD11c or anti-I-A/I-E antibody. Therefore, topical administration of DNA vaccine is an effective route, and may be very useful for the prevention of infectious diseases. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11764291> Leprosy Research Center, National Institute of Infectious Diseases, Higashi-murayama, Tokyo, Japan. norishii@nih.go.jp
• Kraehenbuhl JP (2001). Mucosa-targeted DNA vaccination. Trends Immunol. 22 (12): 646-8. Summary: <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11738975>
• Roche PW, Neupane KD, Failbus SS, Kamath A and Britton WJ (2001). Vaccination with DNA of the Mycobacterium tuberculosis 85B antigen protects mouse foot pad against infection with M. leprae. Int J Lepr Other Mycobact Dis. 69 (2): 93-8. Summary: A DNA vaccine composed of the gene for the common mycobacterial secreted protein antigen 85B was demonstrated to protect the mouse foot pad against infection with Mycobacterium leprae. The protective effect was demonstrated by a 61%-88% reduction in the bacterial number, a protective effect less than that of BCG. The same DNA vaccine has been shown to protect mice against M. tuberculosis infection, and the importance of testing other candidate tuberculosis vaccines for their potential to protect against leprosy is discussed. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11757171> Mycobacterial Research Laboratory, Anandaban Leprosy Hospital, Kathmandu, Nepal. paulwroche@hotmail.com
• Shibui A, Ohmori Y, Suzuki Y, Sasaki M, Nogami S, Sugano S and Watanabe J (2001). Effects of DNA vaccine in murine malaria using a full-length cDNA library. Res Commun Mol Pathol Pharmacol. 109 (3-4): 147-57. Summary: In an attempt to develop a novel malaria vaccine, we constructed a full-length cDNA library from the erythrocytic-stage parasites of Plasmodium berghei ANKA strain using the plasmid vector pCE-FL, which is driven by an EF321 promoter and a CMV-IE enhancer. Here we report the initial trial to screen this library for DNA vaccine candidates against malaria parasite infection in mice. The library of P. berghei was divided into five groups, each representing 2,000 independent clones. Eight female BALB/c mice were injected with these subsets, with an initial injection directly into the spleen, followed by two subsequent intramuscular injections at 1-week intervals. As a control, the plasmid vector without any insert was used. Two weeks after the last injection, 50,000 infected erythrocytes were injected intraperitoneally. Unexpectedly, the survival rate of the vaccinated groups was lower than that of the control (p = 0.053, by Kaplan-Meyer method), suggesting that these DNA vaccines had adverse effects. There was no difference in parasitemia between the two groups. There was no difference between antibody titers before and after immunization in either group. Accelerated deaths in immunized mice occurred from 7 to 10 days after infection, when fur bristling, shivering and convulsions were observed. These observations suggested the possibility that the vaccination had an adverse effect on the cellular immunity that resulted in the development of severe malaria in BALB/c mice, which do not usually develop cerebral malaria. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11758646> Department of Virology, Institute of Medical Science, The University of Tokyo, Japan.
• Stevenson FK, Zhu D and Rice J (2001). New strategies for vaccination and imunomodulation in NHL. Ann Hematol. 80 Suppl 3: B132-4. Summary: Knowledge of the genetic changes which occur in cancer cells is stimulating research aimed towards new therapies. Immunotherapeutic approaches, particularly antibody therapy, are already finding a place in treatment of hematological malignancies. Vaccination will build on experience in the field of infectious diseases, and it should be possible to design vehicles to deliver the expanding range of tumour antigens to the immune system. For DNA vaccines, fusion genes have the potential to activate and direct immune effector pathways. One candidate antigen for B-cell malignancies is the clonal idiotypic immunoglobulin and we have designed a fusion vaccine encoding idiotypic sequence fused to a sequence from a powerful antigen from tetanus toxin. This promotes protective immunity against lymphoma in models, and is now in clinical trial. One challenge is to bring patients into remission without significant damage to immune capacity. Another is to rethink the nature of clinical trials so that more pilot studies of efficacy can be carried out. There is no evidence so far of toxicity due to injection of DNA, but for antigens which are expressed by normal cells, the line between attack on tumour and autoimmunity will have to be carefully drawn. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11757697> Tenovus Laboratory, Southampton University Hospitals Trust, UK. fs@soton.ac.uk