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Detection of Neutralization-sensitive Epitopes in Antigens Displayed on Virus-Like Particle (VLP)-Based Vaccines Using a Capture Assay
Published on: February 10, 2022
A divalent antibody format is required for neutralization of human cytomegalovirus via antigenic domain 2 on
Johan Lantto1, Jean M Fletcher2, Mats Ohlin1
1Department of Immunotechnology, Lund University, PO Box 7031, S-220 07 Lund, Sweden1.
Abstract:
Glycoprotein B (gB) of human cytomegalovirus (HCMV) is the dominating protein in the envelope of this virus and gives rise to virus-neutralizing antibodies in most infected individuals. We have previously isolated a neutralizing human antibody specific for antigenic domain 2 (AD-2) on gB, a poorly immunogenic epitope, which nevertheless is capable of eliciting potent neutralizing antibodies. In order to define parameters important for the neutralization of HCMV via gB, we have investigated the virus-neutralizing capacity and the kinetics of the interaction with AD-2 of the monomeric and dimeric forms of a single chain variable fragment (scFv) corresponding to this antibody. We demonstrate here that neutralization of HCMV via AD-2 on gB can be mediated by dimeric scFv, while monomeric fragments cannot mediate neutralization of the virus, despite a slow dissociation from the intact glycoprotein. This finding is discussed in the context of possible mechanisms for antibody-mediated virus neutralization.
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