Improving Protective Immunity Induced by DNA-Based Immunization: Priming with Antigen and GM-CSF-Encoding Plasmid DNA and Boosting with Antigen-Expressing Recombinant Poxvirus

Sedegah, Martha; Weiss, Walter R.; Sacci, John B.; Charoenvit, Yupin; Hedstrom, Richard C.; Gowda, Kalpana; Majam, Victoria; Tine, John A.; Kumar, Sanjai; Hobart, Peter; Hoffman, Stephen L.

doi:10.4049/jimmunol.164.11.5905

Cited by 118 publications

(81 citation statements)

References 27 publications

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“…Second, recent experiments have shown marked improvements in immunogenicity and efficacy when DNA vaccines are used as part of a heterologous prime-boost vaccination strategy. 19,20,15 It was possible that boosting with recombinant virus would overcome whatever suppressive effect of mixing was observed with DNA vaccines alone. However, in the current experiments, boosting with either of two recombinant vaccinia expressing PfCSP only partially overcame the suppressive effect of mixing on antibody responses to PfCSP (Figure 4a), and had no effect on the suppression of PfCSP-specific IFN-g responses in M9 (Figure 4b).…”

Section: Discussionmentioning

confidence: 99%

“…Detection of antigen-specific IFN-g-producing cells was performed as previously described, 15 with minor modifications. Spleen cells from immunized mice were incubated with previously identified H-2 d restricted Tcell epitopes from antigens of interest, PfCSP(7G8) 39-47 NYDNAGTNL, PfEXP1(3D7) 66-80 EVNKRKSKYK-LATSV, and PfLSA1(3D7) 1671-1679 YYIPHQSSL.…”

Section: Ifn-g Elispotmentioning

confidence: 99%

“…15 Briefly, the effector cells were stimulated by coculture with recombinant ALVACinfected, irradiated P815 cells (for PfSSP2) or 10 mg/ml peptide (for PfCSP, PfEXP1, and PfLSA1, as described above) for 7 days. Targets were recombinant WR vaccinia-infected (PfSSP2) or peptide-pulsed (PfCSP, PfEXP1, and PfLSA1), 51 Cr-loaded P815 cells.…”

Section: Cytotoxic T-cell Assaymentioning

confidence: 99%

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Reduced immunogenicity of DNA vaccine plasmids in mixtures

et al. 2004

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We measured the ability of nine DNA vaccine plasmids encoding candidate malaria vaccine antigens to induce antibodies and interferon-g responses when delivered alone or in a mixture containing all nine plasmids. We further examined the possible immunosuppressive effect of individual plasmids, by assessing a series of mixtures in which each of the nine vaccine plasmids was replaced with a control plasmid. Given alone, each of the vaccine plasmids induced significant antibody titers and, in the four cases for which appropriate assays were available, IFN-g responses. Significant suppression or complete abrogation of responses were seen when the plasmids were pooled in a nine-plasmid cocktail and injected in a single site. Removal of single genes from the mixture frequently reduced the observed suppression. Boosting with recombinant poxvirus increased the antibody response in animals primed with either a single gene or the mixture, but, even after boosting, responses were higher in animals primed with single plasmids than in those primed with the nine-plasmid mixture. Boosting did not overcome the suppressive effect of mixing for IFN-g responses. Interactions between components in a multiplasmid DNA vaccine may limit the ability to use plasmid pools alone to induce responses against multiple targets simultaneously.

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Section: Discussionmentioning

confidence: 99%

Section: Ifn-g Elispotmentioning

confidence: 99%

Section: Cytotoxic T-cell Assaymentioning

confidence: 99%

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Reduced immunogenicity of DNA vaccine plasmids in mixtures

et al. 2004

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“…Our previous murine studies showed that coadministration of murine GM-CSF with P. yoelii CSP plasmid enhanced antibody responses and protective immunity in BALB/c mice. 13,14 Since no antibodies were produced in the first single-gene human trials with PfCSP DNA vaccine, 10,11 human GM-CSF was coadministered with the five-gene mixture vaccine in some of the groups in Preclinical studies with a multigene-malaria DNA vaccine M Sedegah et al the MuSTDO 5 human trial; the analysis of this study is in preparation (TL Richie, unpublished). However, our results here demonstrated that the effects of coadministration of a plasmid expressing mGM-CSF with Pf plasmids are not consistent.…”

Section: Discussionmentioning

confidence: 99%

“…One of the best methods to enhance the immunogenicity of DNA vaccines, particularly antibody response in mice, has been co-immunization with a plasmid expressing granulocyte-macrophage colony-stimulating factor (GM-CSF). 13,14 Based upon the results of these previous studies, the decision was made to produce under good manufacturing practice (GMP) conditions five plasmids (four already studied), each of which expressed a different Plasmodium falciparum protein, PfCSP, PfSSP2, PfExp1, PfLSA1, and PfLSA3. The rationale for the choice of the five proteins has been described.…”

Section: Introductionmentioning

confidence: 99%

Effect on antibody and T-cell responses of mixing five GMP-produced DNA plasmids and administration with plasmid expressing GM-CSF

et al. 2004

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One potential benefit of DNA vaccines is the capacity to elicit antibody and T-cell responses against multiple antigens at the same time by mixing plasmids expressing different proteins. A possible negative effect of such mixing is interference among plasmids regarding immunogenicity. In preparation for a clinical trial, we assessed the immunogenicity of GMP-produced plasmids encoding five Plasmodium falciparum proteins, PfCSP, PfSSP2, PfEXP1, PfLSA1, and PfLSA3, given as a mixture, or alone. The mixture induced higher levels of antibodies against whole parasites than did the individual plasmids, but was associated with a decrease in antibodies to individual P. falciparum proteins. T-cell responses were in general decreased by administration of the mixture. Immune responses to individual plasmids and mixtures were generally higher in inbred mice than in outbreds. In inbred BALB/c and C57BL/6 mice, coadministration of a plasmid expressing murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), increased antibody and T-cell responses, but in outbred CD-1 mice, coadministration of mGM-CSF was associated with a decrease in antibody responses. Such variability in data from studies in different strains of mice underscores the importance of genetic background on immune response and carefully considering the goals of any preclinical studies of vaccine mixtures planned for human trials.

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Prospects for Vaccines to Protect Against AIDS, Tuberculosis, and Malaria

Letvin

Bloom²,

Hoffman³

2001

JAMA

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Given the scope of the worldwide health problems caused by the acquired immunodeficiency syndrome, tuberculosis, and malaria, it is imperative that vaccines be developed to prevent these infections. Recent advances in the understanding of these diseases suggest that T-lymphocyte-mediated immunity is important in containing these infections. The application of novel vaccine technologies for eliciting this type of immunity promises to provide successful vaccines for controlling the spread of these deadly infections.

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Improving Protective Immunity Induced by DNA-Based Immunization: Priming with Antigen and GM-CSF-Encoding Plasmid DNA and Boosting with Antigen-Expressing Recombinant Poxvirus

Cited by 118 publications

References 27 publications

Reduced immunogenicity of DNA vaccine plasmids in mixtures

Reduced immunogenicity of DNA vaccine plasmids in mixtures

Effect on antibody and T-cell responses of mixing five GMP-produced DNA plasmids and administration with plasmid expressing GM-CSF

Prospects for Vaccines to Protect Against AIDS, Tuberculosis, and Malaria

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