Dengue virus neutralization and antibody-dependent enhancement activities of human monoclonal antibodies derived from dengue patients at acute phase of secondary infection

Sasaki, Tadahiro; Setthapramote, Chayanee; Kurosu, Takeshi; Nishimura, Mitsuhiro; Asai, Ayumu; Omokoko, Magot Diata; Pipattanaboon, Chonlatip; Pitaksajjakul, Pannamthip; Limkittikul, Kriengsak; Subchareon, Arunee; Chaichana, Panjaporn; Okabayashi, Tamaki; Hirai, Itaru; Leaungwutiwong, Pornsawan; Misaki, Ryo; Fujiyama, Kazuhito; Ono, Kenichiro; Okuno, Yoshinobu; Ramasoota, Pongrama; Ikuta, Kazuyoshi

doi:10.1016/j.antiviral.2013.03.018

Cited by 43 publications

(50 citation statements)

References 32 publications

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“…All sequences were productive IG rearranged sequences with no stop codon and in-frame junction, except 1 clone (23-5G8E3) have 5 aa insertion at CDR2. Variable region of heavy and light chain of 17 clones of them were submitted to database of DNA Data Bank of Japan (DDBJ) [12].…”

Section: Resultsmentioning

confidence: 99%

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Antibody germline characterization of cross-neutralizing human IgGs against 4 serotypes of dengue virus

Pitaksajjakul

Benjathummarak

Pipattanaboon

et al. 2014

Biochemical and Biophysical Research Communications

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Dengue virus (DENV), a re-emerging virus, constitutes the largest vector-borne disease virus, with 50-100 million cases reported every year. Although DENV infection induces lifelong immunity against viruses of the same serotypes, the subsequent infection with the heterologous serotypes can cause more severe form of the disease, such as Dengue Haemorrhagic Fever (DHF) or Dengue Shock Syndrome (DSS). However, there is neither approved vaccine nor specific drugs available to treat this disease. In this study, previously developed 19 human monoclonal antibodies (HuMAbs) showing strong to moderate cross neutralizing activity were selected. Most of them (13/19) were targeted to domain II of envelop glycoprotein. To understand and clarify the recognition properties, the maturation mechanisms comprising Variable/Diversity/Joining (VDJ) recombination, Variable Heavy (VH)/Variable Light (VL) chain pairing, variability at junctional site, and somatic hypermutation (SHM) of those antibodies were studied and compared with their predecessor germline sequences. IMGT/V-QUEST database was applied to analyze the isolated VH and VL sequences. To confirm the correction of isolated VH/VL, 3 HuMAbs (1A10H7, 1B3B9, 1G7C2) was transiently expressed in HEK293T cell. All three clones of the expressed recombinant IgG (rIgG) showed the same binding and neutralizing activity as same as those from hybridomas. The data obtained in this study will elucidate the properties of those HuMAbs for further genetic modification, and its binding epitopes.

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Section: Resultsmentioning

confidence: 99%

“…They were targeted to envelop protein of DENV. Moreover, thirteen of them were further characterized and found to target to domain II of E protein using truncated E protein [12].…”

Section: Introductionmentioning

confidence: 99%

Antibody germline characterization of cross-neutralizing human IgGs against 4 serotypes of dengue virus

Pitaksajjakul

Benjathummarak

Pipattanaboon

et al. 2014

Biochemical and Biophysical Research Communications

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“…In contrast, we have reported a cell-to-cell fusion method using a new fusion partner cell line, SPYMEG, and donor-derived peripheral blood mononuclear cells (PBMCs) [9,[15][16][17][18]. In this study, we report the characterization of an anti-influenza HuMAb generated from the PBMCs of a volunteer vaccinated with seasonal influenza vaccine.…”

Section: Introductionmentioning

confidence: 65%

A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

Boonsathorn

Panthong

Koksunan

et al. 2014

Biochemical and Biophysical Research Communications

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Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.

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“…Overall, hybridomas previously generated from peripheral blood mononuclear cells isolated from dengue patients secondarily infected with DV26,27 were producers of HuMAbs cross-reactive with JEV-infected cells by immunofluorescence and showed high rates of neutralization against JEV by viral neutralization assay. The clones that cross-reacted with JEV and showed neutralizing activity against JEV were mainly classified into two groups: one contained clones that recognized DV E and were derived from acute-phase, and the other contained clones that recognized DV NS1 and were mostly derived from convalescent-phase.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we reported the preparation of several hybridomas that secrete anti-DV HuMAbs by using peripheral blood mononuclear cells from dengue patients at the acute and convalescent phases of secondary infection with DV 26,27…”

Section: Introductionmentioning

confidence: 99%

Cross-reactivity of human monoclonal antibodies generated with peripheral blood lymphocytes from dengue patients with Japanese encephalitis virus

Pipattanaboon¹,

Sasaki

Nishimura³

et al. 2013

BTT

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BackgroundHybridomas that produce human monoclonal antibodies (HuMAbs) against Dengue virus (DV) had been prepared previously using peripheral blood lymphocytes from patients with DV during the acute and convalescent phases of a secondary infection. Anti-DV envelope glycoprotein (E) 99 clones, anti-DV premembrane protein (prM) 8 clones, and anti-DV nonstructural protein 1 (NS1) 4 clones were derived from four acute-phase patients, and anti-DV E 2 clones, anti-DV prM 2 clones, and anti-DV NS1 8 clones were derived from five convalescent-phase patients.Methods and resultsIn the present study, we examined whether these clones cross-reacted with Japanese encephalitis virus (JEV), which belongs to the same virus family. Forty-six of the above-described 99 (46/99) anti-E, 0/8 anti-prM, and 2/4 anti-NS1 HuMAbs from acute-phase, and 0/2 anti-E, 0/2 anti-prM, and 5/8 anti-NS1 HuMAbs from convalescent-phase showed neutralizing activity against JEV. Thus, most of the anti-E and anti-NS1 (but not the anti-prM) antibodies cross-reacted with JEV and neutralized this virus. Interestingly, 3/46 anti-E HuMAbs derived from acute-phase patients and 3/5 anti-NS1 HuMAbs from convalescent-phase patients showed particularly high neutralizing activity against JEV. Consequently, the HuMAbs showing neutralization against JEV mostly consisted of two populations: one was HuMAbs recognizing DV E and showing neutralization activity against all four DV serotypes (complex-type) and the other was HuMAbs recognizing DV NS1 and showing subcomplex-type cross-reaction with DV.ConclusionAnti-DV E from acute phase (46/99) and anti-DV NS1 (7/12) indicate neutralizing activity against JEV. In particular, three of 46 anti-DV E clones from acute phase and three of five anti-NS1 clones from convalescent phase showed strong neutralizing activity against JEV.

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Dengue virus neutralization and antibody-dependent enhancement activities of human monoclonal antibodies derived from dengue patients at acute phase of secondary infection

Cited by 43 publications

References 32 publications

Antibody germline characterization of cross-neutralizing human IgGs against 4 serotypes of dengue virus

Antibody germline characterization of cross-neutralizing human IgGs against 4 serotypes of dengue virus

A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

Cross-reactivity of human monoclonal antibodies generated with peripheral blood lymphocytes from dengue patients with Japanese encephalitis virus

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