Monoclonal antibodies that cross-react with the E1 glycoprotein of different alphavirus serogroups: characterization including passive protection in vivo

Wust, Carl J.; Nicholas, Judith A.; Fredin, D.; Dodd, D C; Brideau, Roger J.; Levely, Melissa E.; Brown, Arthur

doi:10.1016/0168-1702(89)90009-9

Cited by 21 publications

(14 citation statements)

References 26 publications

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“…Our results give evidence that protection against VEEV disease by scFv-Fc ToR67-3B4 is not necessarily associated with the ability to neutralise VEE virus. The findings reported here are consistent with data from other groups [36], [73], [76]–[78], [80] and we suppose that scFv-Fc ToR67-3B4 binds to a critical site for cell interaction of the VEEV virion either at the level of virus entry, or budding. Whether complement or other Fc effector functions are necessary in VEE virus immunity has to be analysed.…”

Section: Discussionsupporting

confidence: 93%

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Isolation and Characterisation of a Human-Like Antibody Fragment (scFv) That Inactivates VEEV In Vitro and In Vivo

et al. 2012

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Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus genus and several species of this family are pathogenic to humans. The viruses are classified as potential agents of biological warfare and terrorism and sensitive detection as well as effective prophylaxis and antiviral therapies are required.In this work, we describe the isolation of the anti-VEEV single chain Fragment variable (scFv), ToR67-3B4, from a non-human primate (NHP) antibody gene library. We report its recloning into the bivalent scFv-Fc format and further immunological and biochemical characterisation.The scFv-Fc ToR67-3B4 recognised viable as well as formalin and ß-propionolactone (ß-Pl) inactivated virus particles and could be applied for immunoblot analysis of VEEV proteins and immuno-histochemistry of VEEV infected cells. It detected specifically the viral E1 envelope protein of VEEV but did not react with reduced viral glycoprotein preparations suggesting that recognition depends upon conformational epitopes. The recombinant antibody was able to detect multiple VEEV subtypes and displayed only marginal cross-reactivity to other Alphavirus species except for EEEV. In addition, the scFv-Fc fusion described here might be of therapeutic use since it successfully inactivated VEEV in a murine disease model. When the recombinant antibody was administered 6 hours post challenge, 80% to 100% of mice survived lethal VEEV IA/B or IE infection. Forty to sixty percent of mice survived when scFv-Fc ToR67-3B4 was applied 6 hours post challenge with VEEV subtypes II and former IIIA. In combination with E2-neutralising antibodies the NHP antibody isolated here could significantly improve passive protection as well as generic therapy of VEE.

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Section: Discussionsupporting

confidence: 93%

“…Most of them are directed against the E2 protein, only a few targeted the viral E1 protein [61], [62], [69], [73], [78].…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterisation of a Human-Like Antibody Fragment (scFv) That Inactivates VEEV In Vitro and In Vivo

et al. 2012

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“…These findings are in agreement with those of others that determinants recognized by neutralizing antibodies on the membrane proteins of SFV (Greiser-Wilke et al, 1989;Wust et al, 1989) and Sindbis virus (Roehrig et al, 1982;Stanley et al, 1985) are conformational. Furthermore, most epitopes on protein antigens are of a discontinuous nature (Benjamin et al, 1984) and the frequency of peptide-reactive antibodies is low after immunization with native protein (Jemmerson, 1987).…”

Section: Discussionsupporting

confidence: 82%

Identification of linear epitopes on Semliki Forest virus E2 membrane protein and their effectiveness as a synthetic peptide vaccine

Snijders

Benaissa-Trouw

Oosterlaken

et al. 1991

Journal of General Virology

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Semliki Forest virus (SFV) infection of mice was used as a model to study the applicability of synthetic peptides containing only linear epitopes as viral vaccines. The identification of linear epitopes with vaccine potential on the E2 membrane protein of SFV was based on the binding of SFV-specific antibodies to a set of overlapping synthetic hexapeptides (Pepscan) representing the whole E2 amino acid sequence. The 14 available E2-specific monoclonal antibodies which were protective in vivo proved to be unsuitable for the identification of linear epitopes because they recognized only conformational epitopes, as indicated by their lack of reactivity with unfolded, reduced E2 protein on immunoblots. Three epitopes were detected with polyclonal anti-SFV serum at amino acid positions 135 to 141,177 to 185 and 240 to 246 of the E2 protein. Synthetic peptides containing these epitopes were coupled to a carrier protein and tested as a vaccine. Mice immunized with the peptide containing amino acids 240 to 255 of protein E2 were protected against a challenge with virulent SFV but protection of mice immunized with the peptides containing amino acids 126 to 141 or 178 to 186 was only marginally better than that of controls. The prechallenge sera of most peptide-immunized mice reacted with SFVinfected cells but none of these sera neutralized the virus in vitro. However, protection of mice correlated well with SFV-specific antibody titre, suggesting antibody-mediated protection.

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“…Protection against lethal Alphavirus challenge by passive immunization with antibodies that do not inhibit plaque formation was demonstrated previously (41,50). The ability of the six E3-specific MAbs described here to inhibit plaque formation by V3526 virus is not directly relevant to protection against wild-type viral challenge.…”

Section: Discussionmentioning

confidence: 75%

Antibody to the E3 Glycoprotein Protects Mice against Lethal Venezuelan Equine Encephalitis Virus Infection

Parker

Buckley²,

Melanson

et al. 2010

J Virol

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Six monoclonal antibodies were isolated that exhibited specificity for a furin cleavage site deletion mutant (V3526) of Venezuelan equine encephalitis virus (VEEV). These antibodies comprise a single competition group and bound the E3 glycoprotein of VEEV subtype I viruses but failed to bind the E3 glycoprotein of other alphaviruses. These antibodies neutralized V3526 virus infectivity but did not neutralize the parental strain of Trinidad donkey (TrD) VEEV. However, the E3-specific antibodies did inhibit the production of virus from VEEV TrD-infected cells. In addition, passive immunization of mice demonstrated that antibody to the E3 glycoprotein provided protection against lethal VEEV TrD challenge. This is the first recognition of a protective epitope in the E3 glycoprotein. Furthermore, these results indicate that E3 plays a critical role late in the morphogenesis of progeny virus after E3 appears on the surfaces of infected cells.Viruses in the Alphavirus genus of the family Togaviridae are composed of an icosahedral nucleocapsid surrounded by a lipid envelope studded with a distinctive lattice of glycoprotein spikes. The structural proteins of alphaviruses arise through co-and posttranslational processing of a polyprotein encoded by a single 26S mRNA (22,27) in which the order of the gene products is NH 2 -capsid-PE2-6K-E1-COOH. The capsid (C) protein cleaves itself from the nascent polypeptide soon after emergence from the ribosome. The PE2 glycoprotein is a precursor containing the E3 glycoprotein fused to the amino terminus of the E2 envelope glycoprotein. The PE2 glycoprotein is followed by 6K, a small membrane-associated protein, and E1, the second polypeptide component of glycoprotein spikes. Trimerized heterodimers of the E1 and E2 viral glycoproteins form the surface spikes and contain determinants of viral tropism and virulence (1).The E3 glycoprotein acts as a signal for transport of PE2 across the membranes of the rough endoplasmic reticulum (22) and may promote the formation and intracellular transport of E1-PE2 heterodimers (12,23,46) to the cell surface. The E2 glycoprotein promotes specificity of virus binding to the host cell surface and is a target of protective antibodies (7,(18)(19)(20)39). The E1 glycoprotein mediates fusion of the virion envelope with the membranes of acidified endosomes, allowing release of the nucleocapsid into the cytoplasm and the onset of viral replication (21,40,43). Antibodies to the E1 glycoprotein do not typically neutralize virus infectivity in vitro but can protect against lethal challenge in animals (41, 42). During transport to the cell surface, PE2 undergoes a maturational cleavage event by a furin-like protease to produce E2 and E3. The E3 glycoprotein may be subsequently released into the extracellular space (26, 49) or incorporated into the virion (6, 13). At the plasma membrane, trimerized E1-E2 heterodimers are incorporated into the budding virus particle.Mutations that block cleavage of PE2 of Venezuelan equine encephalitis virus (VEEV) are lethal ...

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Monoclonal antibodies that cross-react with the E1 glycoprotein of different alphavirus serogroups: characterization including passive protection in vivo

Cited by 21 publications

References 26 publications

Isolation and Characterisation of a Human-Like Antibody Fragment (scFv) That Inactivates VEEV In Vitro and In Vivo

Isolation and Characterisation of a Human-Like Antibody Fragment (scFv) That Inactivates VEEV In Vitro and In Vivo

Identification of linear epitopes on Semliki Forest virus E2 membrane protein and their effectiveness as a synthetic peptide vaccine

Antibody to the E3 Glycoprotein Protects Mice against Lethal Venezuelan Equine Encephalitis Virus Infection

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