Immunogenicity and efficacy testing in chimpanzees of an oral hepatitis B vaccine based on live recombinant adenovirus.

Lubeck, Michael D.; Davis, Alan R.; Chengalvala, Murty; Natuk, Robert J.; Morin, J E; Molnar-Kimber, Katherine L.; Mason, Bruce B.; Bhat, Bheem M.; Mizutani, Satoshi; Hung, Paul P.

doi:10.1073/pnas.86.17.6763

Cited by 129 publications

(69 citation statements)

References 26 publications

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“…26,27 Chimpanzees infected with vaccinia virus-HBV recombinant were protected against HBV challenge. 28 Recombinant adenovirus also produced HBsAg in vitro 13 and elicited anti-HBs in rabbits 29 and hamsters. 30 The HBV genome consists of a small (approximately 3.2 kb), partially double-stranded, circular DNA molecule.…”

Section: Discussionmentioning

confidence: 99%

Use of SV40 to immunize against hepatitis B surface antigen: implications for the use of SV40 for gene transduction and its use as an immunizing agent

1998

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We have described a novel gene transfer system, in which subcutaneously into mice every 4 weeks. These mice were replication-incompetent, T antigen-deleted simian virus-40 bled every 2 weeks and their sera assayed for antibody (SV40) is used as the transduction vehicle. We report here activity against HBsAg and SV40. Production of anti-HBs successful immunization using such an SV40-derived viral was measured by ELISA and confirmed by Western blot vector. Hepatitis B surface antigen (HBsAg) cDNA was analysis, both of which demonstrated significant levels of cloned downstream of two tandem SV40 early promoters anti-HBs after the second injection. We also tested proto yield a T antigen-deficient SV40 derivative, SV(HBS).duction of anti-SV40 antibodies by the ability of sera to Cultured TC7 cells were exposed to SV(HBS), and neutralize SV(HBS) infectivity. We found no evidence of expression of HBsAg was detected 24 h later by Northern neutralization of SV(HBS) infectivity even after eight inocublot and RT-PCR analysis. Immunochemistry and Western lations. Thus, replication-incompetent SV40 is itself not a blot analysis were also performed 24 h after infection to strong antigen. Our data suggest that SV40-based transdetect expression of HBsAg. Once it was ascertained that duction systems may be a useful vehicle for immunization we could express HBsAg in this way, we used SV(HBS) to and for other gene transfer applications when a need for elicit anti-HBs. SV(HBS) was injected intraperitoneally or multiple inoculations is anticipated.

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Section: Discussionmentioning

confidence: 99%

Use of SV40 to immunize against hepatitis B surface antigen: implications for the use of SV40 for gene transduction and its use as an immunizing agent

1998

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“…22 Recently, oral administration of a vaccine consisting of adenovirus 646 types 4 and 7 encoded with the hepatitis B surface antigen (HBsAg) was evaluated in chimpanzees. 23 Low humoral responses were detected after HBsAg challenge, but when challenged with the hepatitis B virus, 75% of the study population developed resultant infections. Similar results were seen when dogs were given the HBsAg vector orally.…”

Section: Introductionmentioning

confidence: 90%

In vitro and in vivo asessment of adenovirus 41 as a vector for gene delivery to the intestine

et al. 1998

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In order to identify suitable adenoviral vectors for efficient tiated enterocytes, probable targets for oral gene delivery delivery of transgenic proteins and peptides to the intesbut rather resistant to adenovirus-mediated gene transfer, tine, the ability of adenovirus types 5 and 41 (an enter-28.4% of the population internalized the Ad 5 vector and otropic serotype) to bind to and enter undifferentiated and less than 10% bound the virus. Adenovirus 41 was differentiated enterocytes was assessed. FACS analysis efficiently internalized in differentiated enterocytes as showed no significant difference between the virions in 89.6% of the cellular population took up the virus while their ability to bind to undifferentiated Caco-2 cells as 37.4% bound the virus. These results were consistent with 81.6% of the cellular population bound adenovirus 5 (Ad 5) those observed in vivo in rat jejunum. Thus, molecularly and 79.8% bound Ad 41. Both virions were also efficiently engineered Ad 41-based recombinants could be highly internalized in this cell type as 99.6% of the cells took up efficient vectors for delivery of transgenic proteins to differAd 5, while 95.9% took up Ad 41. In studies with differenentiated enterocytes.

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“…In addition to studies in small animals, enteric-coated vaccines were tested in humans and chimpanzees, which were shown to be susceptible to Ad infection in the gut after oral administration of the vaccine. 31 Recombinants of Ad4, Ad5, and Ad7 that express the hepatitis B surface antigen were generated and tested in chimpanzees. [31][32][33] During these trials, no signs of illness that were attributable to the vaccine were noted.…”

Section: Replication-competent Adenovirus Vaccinesmentioning

confidence: 99%

“…31 Recombinants of Ad4, Ad5, and Ad7 that express the hepatitis B surface antigen were generated and tested in chimpanzees. [31][32][33] During these trials, no signs of illness that were attributable to the vaccine were noted. Of particular interest are two reports presenting evidence that an intact E3 region resulted in increased replication of the vaccine virus; 32,33 the E3 region encodes proteins whose function is to protect infected cells from the immune system.…”

Section: Replication-competent Adenovirus Vaccinesmentioning

confidence: 99%

Experimental infections of humans with wild-type adenoviruses and with replication-competent adenovirus vectors: replication, safety, and transmission

Lichtenstein

Wold

2004

Cancer Gene Ther

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Replication-competent (RC) adenoviruses (Ads) are increasingly being developed as oncolytic vectors and as vehicles for delivering vaccine antigens. Although the safety of such vectors in humans is of paramount importance, these vectors pose additional special concerns. Specifically, the prospect of causing Ad-mediated disease in the patient, the amount and sites of Ad replication, the possibility of virus shedding leading to unintended transmission to patient contacts, and the potential for persistence in the inoculated individual must be evaluated. Previous experience with administration of wild-type and RC recombinant Ads to humans may shed light on some of these issues. Experimental infections of humans with natural Ad isolates and RC recombinant vectors show that in adults Ads cause mild or no disease, particularly with Ad serotypes 2 and 5, the serotypes most often used to make recombinant constructs. Other studies show that Ad can replicate in experimentally infected persons, that in some situations Ads can be shed and transmitted to close contacts, and that there is evidence for persistent/latent Ad infection in naturally infected individuals. Overall, these studies indicate that Ads can be safely administered to humans for the treatment of cancer and as antigen delivery vehicles suggesting that the continued development of RC oncolytic and vaccine vectors should be pursued.

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Immunogenicity and efficacy testing in chimpanzees of an oral hepatitis B vaccine based on live recombinant adenovirus.

Cited by 129 publications

References 26 publications

Use of SV40 to immunize against hepatitis B surface antigen: implications for the use of SV40 for gene transduction and its use as an immunizing agent

Use of SV40 to immunize against hepatitis B surface antigen: implications for the use of SV40 for gene transduction and its use as an immunizing agent

In vitro and in vivo asessment of adenovirus 41 as a vector for gene delivery to the intestine

Experimental infections of humans with wild-type adenoviruses and with replication-competent adenovirus vectors: replication, safety, and transmission

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