Monoclonal antibodies against hepatitis A virus

MacGregor, A.; Kornitschuk, M; Hurrell, John G.R.; Lehmann, Noreen I.; Coulepis, A G; Locarnini, SA; Gust, Ian D.

doi:10.1128/jcm.18.5.1237-1243.1983

Cited by 73 publications

(27 citation statements)

References 23 publications

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“…Hepatitis A virus neutralization was tested as previously described (MacGregor et al, 1983;Van Droogenbroeck et al, 2007). Briefly, a dilution series of purified wt HA78 SEC and TKO HA78 SEC was pre-incubated with HepA virus strain JN (Gao, 1989) and appropriate virus target cells (FRhK-4) were infected.…”

Section: Virus Neutralization Assaysmentioning

confidence: 99%

Production of monoclonal antibodies with a controlledN‐glycosylation pattern in seeds ofArabidopsis thaliana

Loos

Droogenbroeck

Hillmer

et al. 2011

Plant Biotechnology Journal

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SummarySeed-specific expression is an appealing alternative technology for the production of recombinant proteins in transgenic plants. Whereas attractive yields of recombinant proteins have been achieved by this method, little attention has been paid to the intracellular deposition and the quality of such products. Here, we demonstrate a comparative study of two antiviral monoclonal antibodies (mAbs) (HA78 against Hepatitis A virus; 2G12 against HIV) expressed in seeds of Arabidopsis wild-type (wt) plants and glycosylation mutants lacking plant specific N-glycan residues. We demonstrate that 2G12 is produced with complex N-glycans at great uniformity in the wt as well as in the glycosylation mutant, carrying a single dominant glycosylation species, GnGnXF and GnGn, respectively. HA78 in contrast, contains additionally to complex N-glycans significant amounts of oligo-mannosidic structures, which are typical for endoplasmic reticulum (ER)-retained proteins. A detailed subcellular localization study demonstrated the deposition of both antibodies virtually exclusively in the extracellular space, illustrating their efficient secretion. In addition, although a KDELtagged version of 2G12 exhibited an ER-typical N-glycosylation pattern, it was surprisingly detected in protein storage vacuoles. The different antibody variants showed different levels of degradation with hardly any degradation products detectable for HA78 carrying GnGnXF glycans. Finally, we demonstrate functional integrity of the HA78 and 2G12 glycoforms using viral inhibition assays. Our data therefore demonstrate the usability of transgenic seeds for the generation of mAbs with a controlled N-glycosylation pattern, thus expanding the possibilities for the production of optimally glycosylated proteins with enhanced biological activities for the use as human therapeutics.

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Section: Virus Neutralization Assaysmentioning

confidence: 99%

Production of monoclonal antibodies with a controlledN‐glycosylation pattern in seeds ofArabidopsis thaliana

Loos

Droogenbroeck

Hillmer

et al. 2011

Plant Biotechnology Journal

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“…Only a single serotype of human HAV has been identified [Lemon and Binn, 1983;MacGregor et al, 1983;Dawson et al, 1984]. Genetic heterogeneity between HAV isolates from different parts of the world enables its classification into seven genotypes, designated I to VII [Robertson et al, 1992].…”

Section: Introductionmentioning

confidence: 99%

Sequential changes in hepatitis A virus genotype distribution in Estonia during 1994 to 2001

Tallo

Nordér

Tefanova³

et al. 2003

Journal of Medical Virology

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Hepatitis A virus (HAV) isolates from a large outbreak and from non-outbreak cases in Estonia were characterized by sequencing the aminoterminal VP1 region. From January 1998 to December 1999, a total of 1084 cases of hepatitis A were reported to the Harjumaa-Tallinn and Ida-Virumaa Health Protection Services in Estonia. The attack rate was highest among males aged 15-29. Initial cases were noted to be associated with injecting drug use. IgM anti-HAV positive sera were available from 107 hospitalized outbreak cases and from 68 patients sampled during 1994 to 2001. HAV RNA was detected in 42% of sera from 1994-1996 and in 88% of sera from 1998-2001. It was possible to obtain HAV sequences from 83 outbreak and 29 background cases. The outbreak strain was represented by five different sequences, all belonging to subtype IIIA. During the outbreak, this IIIA strain also spread into the general population. All available non-outbreak isolates from 1994 to 2001 but one belonged to genotype IA and formed distinct clusters as compared to isolates from other parts of the world. One subtype IIIA isolate from 1995 was unrelated to the outbreak strain. Subtype IA had been dominating in Estonia during 1994-2001, but the outbreak strain from 1998 to 1999 was IIIA. This subtype was encountered previously in addicts in Sweden during the 1980s and in Norway at the end of the 1990s. This study supports the use of limited sequencing within the aminoterminal VP1 region for studying the molecular epidemiology of hepatitis A.

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“…Efficient competitions were detected between M389 and the mouse monoclonal antibodies K2-4F2 (79% inhibition) and K3-4C8 (80% inhibition), which are known to bind to the HAV immunodominant neutralization site [MacGregor et al, 1983;Gao et al, 1989;Schofield et al, 2002;Kim et al, 2004]. Partial competition existed between HAIgG16 and either K2-4F2 (53% inhibition) or K3-4C8 (55% inhibition), as well as between HAIgG78 and K3-4C8 (51% inhibition).…”

Section: Epitope Topography Of the Recombinant Igg Antibodiesmentioning

confidence: 99%

“…Two recombinant antibodies were characterized for HAV neutralization activity as described previously [Reed and Muench, 1938;MacGregor et al, 1983]. Briefly, the HAV virus strain JN [Gao et al, 1989] was propagated in FRhK4 cells, and the 50% tissue-culture infective dose (TCID 50 ) was calculated.…”

Section: Neutralization Test In Vitromentioning

confidence: 99%

Efficient neutralizing activity of cocktailed recombinant human antibodies against hepatitis a virus infection in vitro and in vivo

Cao

Shao

et al. 2008

Journal of Medical Virology

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Hepatitis A virus (HAV) is the major pathogen responsible for acute infectious hepatitis A, a disease that is prevalent worldwide. Although HAV immunization effectively prevents infection, primary immunizations must be administered at least 2 weeks prior to HAV exposure. In contrast, passive immunization with pooled human immunoglobulin (Ig) can provide immediate and rapid protection from HAV infection. Because the use of human sera-derived Igs carries the risk of contamination, we sought to develop recombinant HAV-neutralizing human antibodies. We prepared a combinatorial phage display library of recombinant human anti-HAV antibodies from RNA extracted from the blood lymphocytes of a convalescent hepatitis A patient. Two recombinant human IgG antibodies, HAIgG16 and HAIgG78, were screened from the antibody library by their ability to bind with high affinity to purified, inactivated HAV virions. These antibodies recognized different epitopes of the HAV virion capsid, and competed with both patient sera and well-characterized neutralizing mouse monoclonal antibodies. A cocktailed mixture of HAIgG16 and HAIgG78 at a 3:1 ratio was prepared to compare its combined biological activity with that conferred by each antibody individually. The cocktailed antibodies displayed a stronger neutralizing activity in vitro than that observed with either HAIgG16 and HAIgG78 alone. To determine the in vivo neutralizing abilities of these antibodies, rhesus monkeys were inoculated with cocktailed antibodies and challenged with HAV. Whereas control animals developed hepatitis A and seroconverted to the HAV antibody, animals receiving cocktailed antibodies were protected either from viral infection or from developing clinical hepatitis. These results demonstrate that recombinant human antibody preparations could be used to prevent or treat early-stage HAV infection.

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Monoclonal antibodies against hepatitis A virus

Cited by 73 publications

References 23 publications

Production of monoclonal antibodies with a controlledN‐glycosylation pattern in seeds ofArabidopsis thaliana

Production of monoclonal antibodies with a controlledN‐glycosylation pattern in seeds ofArabidopsis thaliana

Sequential changes in hepatitis A virus genotype distribution in Estonia during 1994 to 2001

Efficient neutralizing activity of cocktailed recombinant human antibodies against hepatitis a virus infection in vitro and in vivo

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