Immunological properties of gene vaccines delivered by different routes

Oliveira, Sérgio C.; Rosinha, G. M. S.; de-Brito, C.F.A.; Fonseca, Cristina Toscano; Afonso, R.R.; Costa, Mirella C.; Góes, Alfredo M.; Rech, E. L.; Azevedo, Vasco

doi:10.1590/s0100-879x1999000200009

Cited by 32 publications

(18 citation statements)

References 30 publications

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“…Together, the results of this study indicate that GeneGun delivery of DNA HIV gp120 or SIV Gag in the presence or absence of adjuvants strongly polarizes antibody responses toward Th2. A Th2 polarization is consistent with some earlier reports (12,24,44,52); however, more-balanced Th1/Th2 responses have been recorded using other antigens pMAX-PRO-SIVmac239-gag ϩ pMAX-PRO-balGP120 Empty pMAX-PRO 14 and 28 3 pMAX-PRO-SIVmac239-gag ϩ pMAX-PRO-balGP120 Empty pMAX-PRO 0, 14, and 28 4 pMAX-PRO-SIVmac239-gag ϩ pMAX-PRO-balGP120 pMAX- PRO-CTA1 28 5 pMAX-PRO-SIVmac239-gag ϩ pMAX-PRO-balGP120 pMAX- PRO-CTA1 14 and 28 6 pMAX-PRO-SIVmac239-gag ϩ pMAX-PRO-balGP120 pMAX-PRO-CTA1 0, 14, and 28…”

Section: Resultssupporting

confidence: 93%

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Adjuvant Activity of the Catalytic A1 Domain of Cholera Toxin for Retroviral Antigens Delivered by GeneGun

Bagley¹,

Lewis²,

Fouts³

2011

Clin. Vaccine Immunol.

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Most DNA-encoded adjuvants enhance immune responses to DNA vaccines in small animals but are less effective in primates. Here, we characterize the adjuvant activity of the catalytic A1 domain of cholera toxin (CTA1) for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) antigens in mice and macaques delivered by GeneGun. The inclusion of CTA1 with SIVmac239 Gag dramatically enhanced anti-Gag antibody responses in mice. The adjuvant effects of CTA1 for the secreted antigen HIV gp120 were much less pronounced than those for Gag, as the responses to gp120 were high in the absence of an adjuvant. CTA1 was a stronger adjuvant for Gag than was granulocyte-macrophage colony-stimulating factor (GM-CSF), and it also displayed a wider dose range than GM-CSF in mice. In macaques, CTA1 modestly enhanced the antibody responses to SIV Gag but potently primed for a recombinant Gag protein boost. The results of this study show that CTA1 is a potent adjuvant for SIV Gag when delivered by GeneGun in mice and that CTA1 provides a potent GeneGun-mediated DNA prime for a heterologous protein boost in macaques.Most DNA vaccines have translated poorly from mice to primates. The exact reasons for this loss of potency are not fully elucidated. This topic is discussed in detail in references 11, 13, 31, and 32. Two strategies to improve the immunogenicity of DNA vaccines for cellular and/or humoral immune responses have evolved in recent years. One utilizes enhanced delivery of the DNA using ballistic particle bombardment with the GeneGun (14) or in vivo electroporation (3). The other main strategy entails the use of plasmid mixtures that combine the DNA vaccine of interest with a plasmid that expresses an adjuvant. The best-studied DNA adjuvants are based on cytokines (9,25,29,30,48) or chemokines (33,53,54). Although several of these adjuvant approaches have shown great promise in small animal models, most have been disappointing in humans and nonhuman primates (11,13,32).Cholera toxin (CT) and the highly related heat-labile enterotoxin of Escherichia coli (LT) have been found to be powerful mucosal immunogens and adjuvants (reviewed in reference 34). In mice, antibody (Ab) responses to CT and bystander antigens last at least 2 years (35, 50). We previously showed that the adjuvant properties of CT can be incorporated into DNA vaccines delivered intramuscularly (i.m.) (7). CT and LT are AB5 enterotoxins produced by Vibrio cholerae and E. coli, respectively. CT and LT consist of catalytic A subunits (separated into A1 and A2 subdomains) anchored in rings of five identical B subunits (43). Their enzymatic active sites reside within the A1 subdomains, while the A2 subdomains anchor the A subunits into the B pentamers (43). The B pentamers of CT and LT bind to gangliosides on cell membranes and facilitate their entry into lysosomes (23). The A1 subdomains are cleaved from the A2 subdomains in the Golgi complex or the endoplasmic reticulum (ER), and then the A1 subdomains exploit host protein retention and degradatio...

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Section: Resultssupporting

confidence: 93%

“…These results are consistent with some (but not all) previous reports (12,24,44,52). Surprisingly, we did not detect cellular immune responses to gp120 or Gag in the GeneGun studies above using ELISPOT assays or CBA.…”

Section: Discussionsupporting

confidence: 94%

Adjuvant Activity of the Catalytic A1 Domain of Cholera Toxin for Retroviral Antigens Delivered by GeneGun

Bagley¹,

Lewis²,

Fouts³

2011

Clin. Vaccine Immunol.

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“…The dominant Th1 phenotype after i.m. gene immunisation and the preferential Th0 type of immune response induced by gene gun vaccination have been reported previously [28,29]. This difference in cytokine pattern has been attributed in part to the dose of DNA administered and the presence of immunostimulatory DNA sequences containing CpG motifs [30,31].…”

Section: Discussionmentioning

confidence: 91%

Induction of a Th1-type of immune response but not protective immunity by intramuscular DNA immunisation with Brucella abortus GroEL heat-shock gene

Leclerq¹,

Harms²,

Rosinha³

et al. 2002

Journal of Medical Microbiology

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The immunogenicity and protective ef®cacy of a DNA vaccine encoding the GroEL heatshock gene from Brucella abortus was tested in BALB/c mice immunised by intramuscular (i.m.) needle injection or epidermally by gene gun. The Brucella GroEL gene was ampli®ed by PCR and cloned into two different mammalian expression vectors pCMV-link and pCMV-tPA. The D17 cell line was transfected with both constructs and GroEL transcripts were detected by Northern blot. To determine the level of protein synthesised, transfected cell lysates were then submitted to Western blot. The nonsecreted form of the recombinant GroEL produced by the pCMV-link construct was detected in much greater amount than the secreted form of the protein produced by the pCMV-tPA construct. After immunisation, a strong anti-GroEL IgG response was detected in mice vaccinated by i.m. injection or gene gun only when the pCMV-link/ GroEL plasmid was used. Regarding the pattern of immune response induced, i.m. needle injection raised a predominantly Th1 response with mostly IgG2a-speci®c antiGroEL and high levels of IFN-ã produced by splenic T cells. Gene gun immunisation induced a Th0 type of immune response in mice characterised by a high IgG1/IgG2a ratio, and IL-4 and interferon (IFN)-ã production. Even though a distinct pattern of immune response was generated depending upon the immunisation route used, neither method engendered a signi®cant level of protection with the GroEL DNA vaccine.

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“…The IgG1 and IgG2a humoral isotype responses against GRA1, GRA7, and ROP2 were analyzed individually in sera from five DNA-vaccinated BALB/c and five DNAvaccinated C3H mice. For comparison, sera from gene gunvaccinated BALB/c mice receiving the gene encoding the Mycobacterium tuberculosis 85A antigen were included because gene gun immunization has been shown to induce pronounced Th2-type humoral responses (28,32,39). As shown in Table 1, gene gun-vaccinated BALB/c mice had titers of IgG1 that were severalfold higher than the IgG2a titers.…”

Section: Humoral Immune Response Induced By Dna Vaccinationmentioning

confidence: 99%

DNA Vaccination with Genes EncodingToxoplasma gondiiAntigens GRA1, GRA7, and ROP2 Induces Partially Protective Immunity against Lethal Challenge in Mice

Vercammen¹,

Scorza²,

Huygen³

et al. 2000

Infect Immun

147

101

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C57BL/6, C3H, and BALB/c mice were vaccinated with plasmids encoding Toxoplasma gondii antigens GRA1, GRA7, and ROP2, previously described as strong inducers of immunity. Seroconversion for the relevant antigen was obtained in the majority of the animals. T. gondii lysate stimulated specific T-cell proliferation and secretion of gamma interferon (IFN-␥) in spleen cell cultures from vaccinated BALB/c and C3H mice but not in those from control mice. Although not proliferating, stimulated splenocytes from DNA-vaccinated C57BL/6 mice also produced IFN-␥. No interleukin-4 was detected in the supernatants of lysate-stimulated splenocytes from DNA-vaccinated mice in any of the mouse strains evaluated. As in infected animals, a high ratio of specific immunoglobulin G2a (IgG2a) to IgG1 antibodies was found in DNA-vaccinated C3H mice, suggesting that a Th1-type response had been induced. For BALB/c mice, the isotype ratio of the antibody response to DNA vaccination was less polarized. The protective potential of DNA vaccination was demonstrated in C3H mice. C3H mice vaccinated with plasmid encoding GRA1, GRA7, or ROP2 were partially protected against a lethal oral challenge with cysts of two different T. gondii strains: survival rates increased from 10% in controls to at least 70% after vaccination in one case and from 50% to at least 90% in the other. In vaccinated C3H mice challenged with a nonlethal T. gondii dose, the number of brain cysts was significantly lower than in controls. DNA vaccination did not protect BALB/c or C57BL/6 mice. Our results demonstrate for the first time in an animal model a partially protective effect of DNA vaccination against T. gondii.

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Immunological properties of gene vaccines delivered by different routes

Cited by 32 publications

References 30 publications

Adjuvant Activity of the Catalytic A1 Domain of Cholera Toxin for Retroviral Antigens Delivered by GeneGun

Adjuvant Activity of the Catalytic A1 Domain of Cholera Toxin for Retroviral Antigens Delivered by GeneGun

Induction of a Th1-type of immune response but not protective immunity by intramuscular DNA immunisation with Brucella abortus GroEL heat-shock gene

DNA Vaccination with Genes EncodingToxoplasma gondiiAntigens GRA1, GRA7, and ROP2 Induces Partially Protective Immunity against Lethal Challenge in Mice

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