Different antibody response to a neutralizing epitope of human cytomegalovirus glycoprotein B among seropositive individuals

Ayata, Minoru; Sugano, Toru; Murayama, Tsugiya; Sakamuro, Daitoku; Takegami, Tsutomu; Matsumoto, Yoh-ichi; Furukawa, Toru

doi:10.1002/jmv.1890430412

Cited by 12 publications

(4 citation statements)

References 22 publications

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“…The other antigenic site maps between amino acids 68 and 84; it is highly conserved among HCMV strains and is recognized by human mAbs with complement-independent neutralizing activity. However, it was recently reported that approximately half of the human sera tested reacted with a fusion protein constructed to express these amino acid sequences [Ayata et al, 1994]. Results of the present study support the idea that the strain-common epitopes located in the extreme amino-terminal sequence of gB elicit antibodies in some, but not all, HCMV-infected individuals.…”

Section: Discussionsupporting

confidence: 88%

Humoral immune response to functional regions of human cytomegalovirus glycoprotein B

et al. 1997

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Sera from patients with primary human cytomegalovirus (HCMV) infections, both acute and convalescent phase, and from HCMV-seropositive healthy subjects were analyzed to determine whether the sera would recognize antigenic domains on HCMV glycoprotein B (gB) that function in virion infectivity and spread of virus from cell to cell. The intact gB molecule, amino-terminal derivatives of different lengths, and internal deletion derivatives were expressed in eukaryotic cells and reacted by immunofluorescence with the sera. All convalescent-phase sera and most sera from healthy seropositive individuals reacted with full-length gB and with an amino-terminal derivative containing 687 amino acids (aa), gB-(1-687); approximately half of the sera recognized an amino-terminal derivative of 447 aa, gB-(1-447), and one-third reacted with the shortest deletion derivative of 258 aa, gB-(1-258). Of the acute-phase sera, 77% recognized intact gB and gB-(1-687), 32% recognized gB-(1-447), and 14% recognized gB-(1-258). Deletion of aa 548 to 618 dramatically reduced the percentage of reactive sera, whereas deletion of aa 411 to 447 had a minor impact on reactivity of sera. To investigate the epitope specificity of human antibodies to gB, we carried out competition experiments between human sera with neutralizing activity and selected monoclonal antibodies (mAbs) to conformational epitopes on gB. We found that antibodies in human sera preclude syncytium formation in UB15-11 glioblastoma cells constitutively expressing gB and compete with certain murine mAbs that block virus entry into cells and transmission of infection from cell to cell. Our results show that HCMV-immune human sera contain antibodies to functional regions on gB, and the abundance of these antibodies in convalescent-phase sera suggests that they may play a central role in limiting dissemination of virus in the host.

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Section: Discussionsupporting

confidence: 88%

Humoral immune response to functional regions of human cytomegalovirus glycoprotein B

et al. 1997

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“…We observed that fewer than 20% (23/140) of the individuals that we sampled in our cohort of healthy subjects had detectable serum levels of antiM2e antibodies. The reasons for this phenomenon are not clear, but a similar situation exists in human CMV, where only a minority of human CMV-seropositive subjects has measurable antibodies to the broadly conserved, neutralizing AD2 epitope within the gB complex of human CMV (25,37,38).…”

Section: Resultsmentioning

confidence: 99%

Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses

Grandea

Olsen

Cox

et al. 2010

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

120

109

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Influenza remains a serious public health threat throughout the world. Vaccines and antivirals are available that can provide protection from infection. However, new viral strains emerge continuously because of the plasticity of the influenza genome, which necessitates annual reformulation of vaccine antigens, and resistance to antivirals can appear rapidly and become entrenched in circulating virus populations. In addition, the spread of new pandemic strains is difficult to contain because of the time required to engineer and manufacture effective vaccines. Monoclonal antibodies that target highly conserved viral epitopes might offer an alternative protection paradigm. Herein we describe the isolation of a panel of monoclonal antibodies derived from the IgG + memory B cells of healthy, human subjects that recognize a previously unknown conformational epitope within the ectodomain of the influenza matrix 2 protein, M2e. This antibody binding region is highly conserved in influenza A viruses, being present in nearly all strains detected to date, including highly pathogenic viruses that infect primarily birds and swine, and the current 2009 swine-origin H1N1 pandemic strain (S-OIV). Furthermore, these human anti-M2e monoclonal antibodies protect mice from lethal challenges with either H5N1 or H1N1 influenza viruses. These results suggest that viral M2e can elicit broadly cross-reactive and protective antibodies in humans. Accordingly, recombinant forms of these human antibodies may provide useful therapeutic agents to protect against infection from a broad spectrum of influenza A strains.

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“…This antigen contains a set of neutralization epitopes, among which antigenic domains 1 (Utz et al ., 1989 ) and 2 (AD-2) (Meyer et al ., 1992 ) are the best characterized. AD-2 is, however, not very immunogenic and induces antibodies in only a fraction of infected individuals (Ayata et al ., 1994 ; Meyer et al ., 1992 ; Navarro et al ., 1997 ; Schoppel et al ., 1997 ). The effective neutralization mediated by AD-2-specific antibodies in vitro has warranted extensive studies and even clinical trials using such reagents (Azuma et al ., 1991 ), despite the fact that only very few antibodies recognizing this epitope have ever been developed (Masuho et al ., 1987 ; Ohlin et al ., 1993 ).…”

Section: Full Textmentioning

confidence: 99%

A divalent antibody format is required for neutralization of human cytomegalovirus via antigenic domain 2 on glycoprotein B

Lantto

Fletcher

Ohlin

2002

Journal of General Virology

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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 antibodymediated virus neutralization.

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Different antibody response to a neutralizing epitope of human cytomegalovirus glycoprotein B among seropositive individuals

Cited by 12 publications

References 22 publications

Humoral immune response to functional regions of human cytomegalovirus glycoprotein B

Humoral immune response to functional regions of human cytomegalovirus glycoprotein B

Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses

A divalent antibody format is required for neutralization of human cytomegalovirus via antigenic domain 2 on glycoprotein B

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