Induction of Potent Humoral and Cell-Mediated Immune Responses Following Direct Injection of DNA Encoding the HIV Type 1<i>env</i>and<i>rev</i>Gene Products

Okuda, Kenji; Bukawa, Hiroki; Hamajima, Kenji; Kawamoto, Susumu; Sekigawa, Kenichiro; Yamada, Yoshihiko; Tanaka, Shun‐ichi; Ishii, Norihisa; Aoki, Ichiro; Nakamura, Masami; Yamamoto, Hiroshi; Cullen, Bryan R.; Fukushima, Jun

doi:10.1089/aid.1995.11.933

Cited by 101 publications

(92 citation statements)

References 51 publications

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“…immunization was previously described (27). Briefly, 100 l of PBS containing 20 g of the DNA vaccine plasmids (15 g of pCMV160IIIB and 5 g of pcREV, hereafter referred to DNA vaccine or pGP160) or 10 g of adjuvant plasmid, or both, was inoculated directly into the gastrocnemius muscle of mice.…”

Section: Immunizationmentioning

confidence: 99%

The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine

Kusakabe¹,

Xin²,

Katoh³

et al. 2000

The Journal of Immunology

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120

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The mechanism of immune activation induced by a plasmid-encoding GM-CSF (pGM-CSF), administered in combination with a DNA vaccine encoding the envelope of HIV, was studied. Injecting pGM-CSF i.m. into mice 3 days before DNA vaccination primarily induced a Th2 response. Simultaneous administration of the DNA vaccine plus pGM-CSF activated both a Th1 and a Th2 response. When the plasmid was injected 3 days after DNA vaccination, enhancement of Th1 immunity predominated. These results suggest that the timing of cytokine expression determines the phenotype of the resultant Th response. After 3 days of pGM-CSF injection, the increased percentages of CD11c+, CD8+ cells were observed in the regional lymph nodes. In addition, many infiltrated cells, including S-100 protein-positive cells, were found in the pGM-CSF-injected tissue. The importance of these S-100+ cells or both CD8+ and CD11c+ cells, especially that of dendritic cells (DCs), was also studied. DCs derived from bone marrow and cultured in RPMI 1640 medium containing IL-4 and GM-CSF were incubated with DNA vaccine and then transferred into naive mice. Mice receiving DCs showed strong HIV-1-specific Th2 immune responses. Our results suggest that DCs play important roles in the activation or modification of the Th2-type immune response induced by DNA vaccination.

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Section: Immunizationmentioning

confidence: 99%

The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine

Kusakabe¹,

Xin²,

Katoh³

et al. 2000

The Journal of Immunology

Self Cite

120

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“…1 We previously developed an HIV-1 DNA vaccine constructed from expression plasmids harboring a CMV promoter. 6 In order to enhance the immune response induced by the vaccine, in this study, we examined the adjuvant effect of 8 Br-cAMP. Our results indicate that both i.m.…”

Section: Discussionmentioning

confidence: 99%

“…The vaccine plasmids, pCMV160IIIB encoding HIV-1 IIIB env and pCMVREV encoding HIV-1 rev, have been previously described. 6 8 Br-cAMP was purchased from Sigma (St Louis, MO, USA). Each group consisted of five to six mice.…”

Section: Animals and Plasmidsmentioning

confidence: 99%

“…An ELISA was performed as described elsewhere. 6 Briefly, 96-well microtiter plates were coated with 5 g/ml of HIV-1 IIIB V3 peptide (NNTRKSIRIQRGPGRAFVTIGKIGN)-multiple antigenic peptide (MAP). The wells were treated with PBS containing 1% bovine serum albumin (BSA) and incubated for 1 h at room temperature.…”

Section: Enzyme-linked Immunosorbent Assay (Elisa)mentioning

confidence: 99%

“…This vaccine is able to induce an increase in the levels of HIV-1-specific humoral and cellular immune responses in BALB/c mice and M. fuscata monkeys. 6 In order to increase the effectiveness of the vaccine, several adjuvants have been recently introduced, including a DNA plasmid encoding immunomodulatory cytokines, 7-11 costimulatory molecules [12][13][14][15] and cationic lipids for improving DNA delivery. 16 In the present study, we evaluated the ability of 8 Br-cAMP to enhance DNA-vaccine-induced immune responses to the HIV-1 Env product derived from the expression cassette controlled by the CMV promoter, which is known to be easily up-regulated by an elevation in the level of intracellular cAMP.…”

Section: Introductionmentioning

confidence: 99%

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8 Br-cAMP enhances both humoral and cell-mediated immune responses induced by an HIV-1 DNA vaccine

Arai

Hamajima

et al. 2000

Gene Ther

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From a series of preclinical studies and animal experiments, we have been able to demonstrate that DNA vaccines are a promising tool in strategies for protecting hosts from a variety of infectious diseases. Since the promoter activity of the human cytomegalovirus immediate-early promoter/ enhancer (CMV promoter) is known to be responsive to an elevation in the level of intracellular cAMP, we hypothesized that use of cAMP analogue (8-Bromo adenosine 3Ј5Ј-cyclic monophosphate, 8 Br-cAMP) would increase the level of transgene expression supported by the CMV, and enhance the ability of DNA vaccines to evoke an immune response against the transgene product in vivo. To evaluate this hypothesis, immune responses against HIV-1 envelope protein, gp160, an immunogenic HIV-1 component expressed under the control of the CMV promoter, were evaluated in BALB/c mice with or without stimulation by 8 Br-cAMP. DNA vaccine with 8 Br-cAMP was intramuscularly (i.m.) or intranasally (i.n.) administered to BALB/c mice twice on days 0 and 14. Regardless of which route was used, the combination increased the serum IgG antibody (Ab) titer, HIV-1-

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Induction of HIV-1 Nef-specific cytotoxic T lymphocytes by Nef-expressing DNA vaccine

et al. 1996

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Recently, some individuals who have remained seronegative despite definite exposure to HIV-1 have been reported. Among these individuals, an unusually high frequency of HIV-1 Nef-specific cytotoxic T lymphocytes was observed. Direct injection of plasmid DNA encoding foreign antigen can elicit both cell-mediated immunity and antibody responses (DNA vaccine). We constructed an HIV-1 Nef-expressing plasmid, and we induced HIV-1 Nef-specific cytotoxic T lymphocytes. This is the first report of inducing HIV-1 Nef-specific cytotoxic T lymphocytes by DNA vaccine.

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Induction of Potent Humoral and Cell-Mediated Immune Responses Following Direct Injection of DNA Encoding the HIV Type 1envandrevGene Products

Cited by 101 publications

References 51 publications

The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine

The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine

8 Br-cAMP enhances both humoral and cell-mediated immune responses induced by an HIV-1 DNA vaccine

Induction of HIV-1 Nef-specific cytotoxic T lymphocytes by Nef-expressing DNA vaccine

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