Safety, tolerability and humoral immune responses after intramuscular administration of a malaria DNA vaccine to healthy adult volunteers

Le, Thong P.; Coonan, Kevin M.; Hedstrom, Richard C.; Charoenvit, Yupin; Sedegah, Martha; Epstein, Judith E.; Kumar, Sanjai; Wang, Ruobing; Doolan, Denise L.; Maguire, Jason D.; Parker, Suezanne E.; Hobart, Peter; Norman, Jon; Hoffman, Stephen L.

doi:10.1016/s0264-410x(99)00407-7

Cited by 223 publications

(124 citation statements)

References 30 publications

Supporting

Mentioning

121

Contrasting

Unclassified

Order By: Relevance

“…4,10,11,13 VCL-2556 (LSA3) was constructed by cloning the full-length LSA-3 gene into the BamHI site of the mammalian expression plasmid VR1020. The LSA3 gene was amplified from the blood stage cDNA of the 3D7 strain of P. falciparum.…”

Section: Plasmidsmentioning

confidence: 99%

“…IFAT: Using previously described methods, 11 IFAT was carried out using P. falciparum air-dried sporozoites, cryosections of chimpanzee livers infected with P. falciparum liver stage parasites, and air-dried parasitized erythrocytes obtained from in vitro parasite cultures.…”

Section: Immunization Groupsmentioning

confidence: 99%

“…Our lab has systematically studied DNA malaria vaccines, either as single plasmids or as combinations in mice, 2-4 rabbits, 5 non-human primates, [6][7][8][9] and humans. [10][11][12] Additionally, we have also studied multiple methods to enhance the immunogenicity and protective efficacy of DNA vaccines in murine and non-human primate systems. 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).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2004

View full text Add to dashboard Cite

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.

show abstract

Section: Plasmidsmentioning

confidence: 99%

Section: Immunization Groupsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Although DNA vaccines have thus far performed poorly in clinical trials, [23][24][25] their efficacy in preclinical small rodent models against infectious diseases or cancers has been impressive. 26,27,[4][5][6] DNA vaccines are easy to construct and they induce a full spectrum of immune responses including CD8 + T cells, 26 which have been implicated to play a major role in tumor cell eradication.…”

Section: Discussionmentioning

confidence: 99%

A DNA vaccine expressing tyrosinase-related protein-2 induces T-cell-mediated protection against mouse glioblastoma

et al. 2003

View full text Add to dashboard Cite

A mouse glioblastoma cell line, termed GL261, was shown to express high levels of proteins involved in melanin biosynthesis such as the tyrosinase-related protein-2 (TRP-2), which is commonly overexpressed in melanoma cells. Mice injected with GL261 cells developed a CD8 + T-cell response to TRP-2 and a DNA vaccine expressing human (h)TRP-2 induced CD8 + T cells that recognized TRP-2 expressed by GL261 cells indicating that this melanoma-associated antigen may be suited for active immunotherapy of glioblastoma. Mice vaccinated with a DNA vaccine expressing TRP-2 were partially protected against subcutaneous, intravenous, or intracerebral challenge with the glioblastoma cells. Vaccine-induced protection against intracerebral challenge required both CD4 + and CD8 + T cells. Vaccine efficacy was enhanced upon addition of IL-12 as a genetic adjuvant. These results indicate that this well-defined melanoma-associated antigen can induce an adaptive immune response, which limits the intracerebral progression of a glioblastoma.

show abstract

“…Clinical trials have shown that they are nontoxic and well tolerated, though the responses their vaccination induce are low and vary from one individual to another, [1][2][3] while their efficacy is often limited by low levels of gene and protein expression and the complex requirements for protein presentation and lymphocyte activation. 4 Enhancement of the potency of DNA vaccines has been sought through the employment of costimulatory molecules and cytokines as adjuvants.…”

Section: Introductionmentioning

confidence: 99%

Insertion of the DNA for the 163–171 peptide of IL1β enables a DNA vaccine encoding p185neu to inhibit mammary carcinogenesis in Her-2/neu transgenic BALB/c mice

et al. 2001

View full text Add to dashboard Cite

An assessment was made of the effectiveness of DNA vaccination in prevention of the mammary adenocarcinomas of BALB/c female mice transgenic for the activated rat Her-2/neu oncogene. Atypical hyperplasia is evident in their mammary glands when they are 6 weeks old and in situ carcinoma by the 13th week. Palpable invasive carcinomas appear around the 17th week and are always evident in all 10 glands by the 33rd week. Intramuscular vaccinations with 100 g plasmid DNA encoding the extracellular domain of the Her-2/neu p185 (ECD) performed at the 6th, 12th, 18th and 24th week provided no significant protection, whereas those ECD plasmids in which the DNA coding for the

show abstract

Safety, tolerability and humoral immune responses after intramuscular administration of a malaria DNA vaccine to healthy adult volunteers

Cited by 223 publications

References 30 publications

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

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

A DNA vaccine expressing tyrosinase-related protein-2 induces T-cell-mediated protection against mouse glioblastoma

Insertion of the DNA for the 163–171 peptide of IL1β enables a DNA vaccine encoding p185neu to inhibit mammary carcinogenesis in Her-2/neu transgenic BALB/c mice

Contact Info

Product

Resources

About