Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein

Cooney, Elizabeth; Collier, Ann C.; Greenberg, Philip D.; Coombs, Robert W.; Zarling, Joyce M.; Arditti, D. E.; Hoffman, Michelle; Hu, Shiu Lok; Corey, Lawrence

doi:10.1016/0140-6736(91)91636-9

Cited by 319 publications

(174 citation statements)

References 18 publications

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“…Further studies on the mechanisms for this preventive effect suggest that the therapeutic effect of rVV-GAD65 was due to the induction of immunological tolerance through the active suppression of effector T cells by the induction of Th2 immune responses, rather than clonal deletion or clonal anergy. As no serious side-effects were found in healthy human subjects that received percutaneous administration of vaccinia virus [23,24], a recombinant vaccinia virus expressing GAD might have therapeutic value for the prevention of Type I diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…For example, animals immunised with rVV expressing a protein from a pathogenic virus are protected from the disease caused by challenge with that virus [21,22]. Of note too, in Phase I clinical trials with vaccinia virus expressing the human immunodeficiency virus 1 envelope gene, no serious side effects were found in healthy subjects that received percutaneous administration [23,24]. These advantages of rVV would make it valuable for clinical use in Type I diabetes, if the administration of rVV expressing beta-cell autoantigen proteins such as GAD can tolerise the autoreactive T cells and prevent the development of diabetes.…”

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confidence: 99%

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Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase

et al. 2002

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Aims/hypotheses. Type I (insulin-dependent) diabetes mellitus results from T-cell-mediated autoimmune destruction of pancreatic beta cells. Among the beta-cell autoantigens that have been implicated in triggering of beta-cell-specific autoimmunity, glutamic acid decarboxylase (GAD) is a strong candidate in both humans and the NOD mouse. We aimed to determine whether treatment with a recombinant vaccinia virus expressing GAD (rVV-GAD65) could prevent the development of diabetes in NOD mice. Methods. Three-eight-to-nine-week-old female NOD mice were injected with various doses of rVV-GAD65 or rVV-MJ601as a control. We then examined the incidence of diabetes, T-cell proliferative response to GAD, amounts of anti-GAD IgGs, cytokine production and generation of regulatory cell populations. Results. Administration of rVV-GAD65 to NOD mice prevented diabetes in an age-dependent and dose-dependent manner. Splenic T cells from rVV-GAD65-treated mice did not proliferate in response to GAD65.The amount of IgG1 was increased, whereas IgG2a amounts did not change in rVV-GAD65-treated NOD mice. The production of interleukin-4 increased, whereas the production of interferon-γ decreased in rVV-GAD65-treated mice after stimulation with GAD. Furthermore, splenocytes from rVV-GAD65-treated NOD mice prevented the transfer of diabetes by splenocytes from acutely diabetic NOD mice in NOD.scid recipients. Conclusion/interpretation. Immunogene therapy using a recombinant vaccinia virus expressing GAD results in the prevention of autoimmune diabetes in NOD mice by the induction of immunological tolerance through active suppression of effector T cells, and this treatment might have therapeutic value for the prevention of Type I diabetes. [Diabetologia (2002)

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase

et al. 2002

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“…The wt virus alone will trigger a cytokine cascade and recruit helper T lymphocytes to the injection site. 21 The virus has been used successfully for gene insertion in patients at risk for AIDs 22 and in colon cancer patients. 23 The large size of the virus allows it to serve as a carrier for multiple genes as needed.…”

Section: Discussionmentioning

confidence: 99%

Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma

et al. 1999

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Seven immunocompetent, revaccinated patients with surgically incurable cutaneous melanoma underwent treatment of dermal and/or subcutaneous metastases with twice-weekly intratumoral injections of escalating doses (10 4 Ϫ2 ϫ 10 7 plaque-forming units (PFU)/lesion; 10 4 Ϫ8 ϫ 10 7 PFU/session) of a vaccinia/GM-CSF recombinant virus for 6 weeks. Patients with stable or responding disease were maintained on treatment until tumor resolution or progression. Systemic toxicity was infrequent, dose-related, and limited to mild flu-like symptoms that resolved within 24 hours. Local inflammation, at times with pustule formation, was consistently seen with doses of Ն10 7 PFU/lesion. Chronically treated lesions showed a dense infiltration, with CD4 ϩ and CD8 ϩ lymphocytes, histiocytes, and eosinophils. All seven patients developed an antivaccinia humoral immune response 14 -21 days following revaccination. Despite the presence of these antivaccinia antibodies, the reporter gene was expressed, as judged by the development of anti-␤-galactosidase antibodies in all patients. Passenger cytokine gene function was evidenced by the presence of virally encoded GM-CSF mRNA at injection sites both early (weeks 1 and 5) and late (week 31) in the course of treatment. Eosinophilia at treatment sites indicated that physiologically significant levels of functional cytokine were generated. However, there were no changes in the total number of peripheral white blood cells or in the numbers or percentages of polymorphonuclear leukocytes, monocytes, or eosinophils. GM-CSF was not detected in the sera. The two patients with the largest tumor burdens failed to respond even at treatment sites. Three patients had mixed responses, with regression of treated and untreated dermal metastases and progression of disease elsewhere. One patient had a partial response, with regression of injected and uninjected regional dermal metastases. Residual melanoma was excised, rendering the patient disease free. One patient with only dermal metastases confined to the scalp achieved a complete remission. Sequential administration of escalating doses of a GM-CSF recombinant vaccinia virus is safe, effective at maintaining passenger gene function, and can induce tumor regression.

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“…67 -70 The VV GA733 -2 construct described here is a candidate vaccine for patients with CRC. However, a concern pertaining to the use of recombinant VV vaccines in patients is whether previous exposure to the virus ( most patients >50 years of age are seropositive for VV ) negatively affects induction of Ag -specific immunity by recombinant VV, 71 although repeated immunization of CRC patients with VV CEA induced immune responses in the majority of patients. 71 VV GA733 -2 may be especially valuable for combined vaccinations of cancer patients with Ad GA733 -2, which induces humoral, cellular, and protective immune responses in mice.…”

Section: Cancer Gene Therapymentioning

confidence: 99%

“…However, a concern pertaining to the use of recombinant VV vaccines in patients is whether previous exposure to the virus ( most patients >50 years of age are seropositive for VV ) negatively affects induction of Ag -specific immunity by recombinant VV, 71 although repeated immunization of CRC patients with VV CEA induced immune responses in the majority of patients. 71 VV GA733 -2 may be especially valuable for combined vaccinations of cancer patients with Ad GA733 -2, which induces humoral, cellular, and protective immune responses in mice. 30 Sequential immunization with different recombinant viruses has shown superior antitumor effects compared with immunizations with a single virus, 38,39 due possibly to the enhanced boosting of the tumor Ag -specific compared with virus -specific immune responses when different viruses are used in combination.…”

Section: Cancer Gene Therapymentioning

confidence: 99%

Inhibition of tumor growth by recombinant vaccinia virus expressing GA733/CO17-1A/EpCAM/KSA/KS1-4 antigen in mice

Žaloudík

Jacob

et al. 2002

Cancer Gene Ther

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The human colorectal carcinoma ( CRC ) -associated GA733 antigen ( Ag ), also named CO17 -1A / EpCAM / KSA / KS1 -4, has been a useful target in passive immunotherapy of CRC patients with monoclonal antibody ( mAb ) and in active immunotherapy with antiidiotypic antibodies or with recombinant protein. These approaches have targeted single epitopes ( monoclonal anti -GA733 antibodies and anti -idiotypic antibodies ) or extracellular domain epitopes ( recombinant protein ), primarily by B cells. To determine whether a reagent that induces immunity to a larger number of both B -and T -cell epitopes might represent a superior vaccine, we analyzed the capacity of full -length GA733 Ag expressing multiple potentially immunogenic epitopes and encoded by recombinant vaccinia virus ( VV GA733 -2 ) to induce humoral, cellular, and / or protective immunity in mice. VV GA733 -2 induced Ag -specific antibodies that reacted predominantly to unknown epitopes on the Ag and lysed Ag -positive CRC targets in conjunction with murine peritoneal macrophages as effector cells. Immunized mice developed Ag -specific, proliferative and delayed -type hypersensitive lymphocytes. VV GA733 -2 inhibited growth of ras -transformed syngeneic tumor cells expressing the human GA733 Ag in mice. These results suggest the potential of VV GA733 -2 as a candidate vaccine for patients with CRC, possibly in combination with recombinant GA733 -2 -expressing adenovirus, which has been shown to induce cytolytic antibodies and T cells as well as tumor protective effects in mice. The combined vaccine approach may be superior to the use of either vaccine alone in patients who are pre -immune to both viruses.

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Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein

Cited by 319 publications

References 18 publications

Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase

Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase

Intratumoral recombinant GM-CSF-encoding virus as gene therapy in patients with cutaneous melanoma

Inhibition of tumor growth by recombinant vaccinia virus expressing GA733/CO17-1A/EpCAM/KSA/KS1-4 antigen in mice

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