Experimental Infection of Chimpanzees with the Virus of Hepatitis B

Maynard, James E.; Berquist, Kenneth R.; Krushak, Donald H.; Purcell, Robert H.

doi:10.1038/237514a0

Cited by 62 publications

(27 citation statements)

References 7 publications

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“…The host range of human HBV is narrow: to date, productive infections have been established only in human beings and higher primates (16)(17)(18)(19). In permissive hosts, viral antigens (20) and DNA are found primarily within liver cells, which harbor abundant quantities of replicative and assembly intermediates as well as mature virions.…”

Section: The Biology Of Hbv Infectionmentioning

confidence: 99%

The Molecular Biology of the Hepatitis B Viruses

Ganem¹,

Varmus²

1987

Annu. Rev. Biochem.

1,014

591

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Section: The Biology Of Hbv Infectionmentioning

confidence: 99%

The Molecular Biology of the Hepatitis B Viruses

Ganem¹,

Varmus²

1987

Annu. Rev. Biochem.

1,014

591

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“…Anti-HBs responses are expressed in milliinternational units (mIU), based on a conversion factor of 3.5 RIA units per 1 mIU). Sera were further tested for HBsAg by RIA (Ausria 11-125), for anti-HBc (HBV core antigen) antibodies by a competition RIA (Corab, Abbott), alanine aminotransaminase (ALT) (20), and anti-adenovirus antibodies by microneutralization analysis on A549 cell monolayers using a challenge dose of 30-100 50% tissue culture infectivity doses (8).…”

Section: Methodsmentioning

confidence: 99%

“…1). HBsAg was secreted into the medium by cells infected with Wy-Ad7HZ6-1 and was found to consist of spherical particles (predominantly [20][21][22][23][24][25] . Entericcoated capsules containing Ad7 and Wy-Ad4HHxHS were prepared as described above except that viruses were obtained directly from infected cell lysates.…”

Section: Methodsmentioning

confidence: 99%

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

Lubeck¹,

Davis²,

Chengalvala³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

129

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As a major cause of acute and chronic liver disease as well as hepatocellular carcinoma, hepatitis B virus (HBV) continues to pose significant health problems worldwide. Recombinant hepatitis B vaccines based on adenovirus vectors have been developed to address global needs for effective control of hepatitits B infection. Although considerable progress has been made in the construction ofrecombinant adenoviruses that express large amounts of HBV gene products, preclinical immunogenicity and efficacy testing of candidate vaccines has remained difficult due to the lack of a suitable animal model. We demonstrate here that chimpanzees are susceptible to enteric infection by human adenoviruses type 7 (Ad7) and type 4 (Ad4) following oral admiistrtion of live virus. Moreover, after sequential oral immunization with Ad7-and Ad4-vectored vaccines containing the hepatitis B surface antigen (HBsAg) gene, significant antibody responses to HBsAg (anti-HBs) were induced in two chimpanzees. After challenge with heterologous HBV, one chimpanzee was protected from acute hepatitis and the other chimpanzee experienced modified HBV-induced disease. These data demonstrate the feasibility of using orally administered recombinant adenoviruses as a general approach to vaccination.

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“…Sequence analysis finally showed that HBV is also indigenous to chimpanzees and other nonhuman primates (Vaudin et al 1988;Grethe et al 2000). In 1972 and the years following, it was conclusively shown that HBV sera -negative chimpanzees were susceptible to infection with human HBV isolates (Maynard et al 1972;Barker et al 1973Barker et al , 1975aMarkenson et al 1975). These crucial experiments paved the way for future prospective studies of HBV infections, vaccine development, and therapeutic interventions as discussed in the next sections.…”

mentioning

confidence: 99%

“…However, it was not known whether chimpanzees were native hosts of HBVor whether they contracted HBV as a result of transmission from humans. In the early 1970s, it was shown that chimpanzees were fully susceptible to infection with HBV present in human plasma (Maynard et al 1972;Barker et al 1973). Much later, HBV strains indigenous to chimpanzees and other nonhuman primates were discovered (Norder et al 1996;Lanford et al 1998Lanford et al , 2000Warren et al 1999;Grethe et al 2000;Hu et al 2000Hu et al , 2001MacDonald et al 2000;Takahashi et al 2000Takahashi et al , 2001Vartanian et al 2002;Sall et al 2005;Dupinay et al 2013).…”

mentioning

confidence: 99%

The Chimpanzee Model for Hepatitis B Virus Infection

Wieland

2015

Cold Spring Harbor Perspectives in Medicine

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Even before the discovery of hepatitis B virus (HBV), it was known that chimpanzees (Pan troglodytes) are susceptible to human hepatitis viruses. The chimpanzee is the only primate animal model for HBV infections. Much like HBV-infected human patients, chimpanzees can developacute andchronic HBVinfectionsand consequent hepatitis. Chimpanzees alsodevelop a cellular immune response similar to that observed in humans. For these reasons, the chimpanzee has proven to be an invaluable model for investigations on HBV-driven disease pathogenesis and also the testing of novel antiviral therapies and prophylactic approaches.

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Experimental Infection of Chimpanzees with the Virus of Hepatitis B

Cited by 62 publications

References 7 publications

The Molecular Biology of the Hepatitis B Viruses

The Molecular Biology of the Hepatitis B Viruses

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

The Chimpanzee Model for Hepatitis B Virus Infection

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