Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors

Kubota‐Koketsu, Ritsuko; Mizuta, Hiroyuki; Oshita, Masatoshi; Ideno, Shoji; Yunoki, Mikihiro; Kuhara, Motoki; Yamamoto, Naomasa; Okuno, Yoshinobu; Ikuta, Kazuyoshi

doi:10.1016/j.bbrc.2009.06.151

Cited by 47 publications

(58 citation statements)

References 27 publications

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“…It has been reported that there exist highly conserved epitopes in the stem region of the HA molecule that may become a target for a "universal flu vaccine" (3,7,10,14,15). Humanized monoclonal antibodies raised against these conserved epitopes from a single influenza virus strain were shown to provide strong cross-protection against heterologous strains (13).…”

Section: Discussionmentioning

confidence: 99%

Cross-Protection of Chicken Immunoglobulin Y Antibodies against H5N1 and H1N1 Viruses Passively Administered in Mice

Wallach¹,

Webby²,

Islam³

et al. 2011

Clin. Vaccine Immunol.

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Influenza viruses remain a major threat to global health due to their ability to undergo change through antigenic drift and antigenic shift. We postulated that avian IgY antibodies represent a low-cost, effective, and well-tolerated approach that can easily be scaled up to produce enormous quantities of protective antibodies. These IgY antibodies can be administered passively in humans (orally and intranasally) and can be used quickly and safely to help in the fight against an influenza pandemic. In this study, we raised IgY antibodies against H1N1, H3N2, and H5N1 influenza viruses. We demonstrated that, using whole inactivated viruses alone and in combination to immunize hens, we were able to induce a high level of anti-influenza virus IgY in the sera and eggs, which lasted for at least 2 months after two immunizations. Furthermore, we found that by use of in vitro assays to test for the ability of IgY to inhibit hemagglutination (HI test) and virus infectivity (serum neutralization test), IgYs inhibited the homologous as well as in some cases heterologous clades and strains of viruses. Using an in vivo mouse model system, we found that, when administered intranasally 1 h prior to infection, IgY to H5N1 protected 100% of the mice against lethal challenge with H5N1. Of particular interest was the finding that IgY to H5N1 cross-protected against A/Puerto Rico/8/34 (H1N1) both in vitro and in vivo. Based on our results, we conclude that anti-influenza virus IgY can be used to help prevent influenza virus infection.

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Section: Discussionmentioning

confidence: 99%

Cross-Protection of Chicken Immunoglobulin Y Antibodies against H5N1 and H1N1 Viruses Passively Administered in Mice

Wallach¹,

Webby²,

Islam³

et al. 2011

Clin. Vaccine Immunol.

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“…3C. One study identified an epitope that is distinct from those identified in our cluster analysis; interestingly, this epitope is from an antibody isolated from a human volunteer, which was found to bind to a relatively conserved region of H3 HA at positions 173 to 181 (18).…”

Section: Mapping Clusters To Established Regions Figures S1 and S2mentioning

confidence: 63%

“…Given their wide coverage in the literature, we shall refer to these regions as the "canonical" antigenic regions. More recently, the ability to isolate and clone anti-HA antibodies from human volunteers prompted a number of studies (18,24,25,39).…”

Section: Characteristics Of Antibody Binding In Influenza a Virus Hemmentioning

confidence: 99%

Analysis of Antigenically Important Residues in Human Influenza A Virus in Terms of B-Cell Epitopes

Lees

Moss

Shepherd

2011

J Virol

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In this paper we undertake an analysis of the antigenicity of influenza A virus hemagglutinin. We developed a novel computational approach to the identification of antigenically active regions and showed that the amino acid substitutions between successive predominant seasonal strains form clusters that are consistent, in terms of both their location and their size, with the properties of B-cell epitopes in general and with those epitopes that have been identified experimentally in influenza A virus hemagglutinin to date. Such an interpretation provides a biologically plausible framework for an understanding of the location of antigenically important substitutions that is more specific than the canonical "antigenic site" model and provides an effective basis for deriving models that predict antigenic escape in the H3N2 subtype. Our results support recent indications that antibodies binding to the "stalk" region of hemagglutinin are found in the human population and exert evolutionary pressure on the virus. Our computational approach provides a possible method for identifying antigenic escape through evolution in this region, which in some cases will not be identified by the hemagglutinin inhibition assay.

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“…A very unique heterohybridoma fusion partner denoted SPYMEG was developed by fusion of Sp2 murine myeloma cells and MEG-01 human megakaryoblastic leukemia cells (74). Recently, SPYMEG was employed for the production of anti-influenza mAbs, generated by fusing PBMCs from influenza-vaccinated and naturally infected volunteers (75,76). It was also used successfully to make human hybridomas secreting anti-HIV neutralizing mAbs by fusion with PBMCs obtained from HIV-1-infected individuals (77).…”

Section: Fusion Partnersmentioning

confidence: 99%

Use of Human Hybridoma Technology To Isolate Human Monoclonal Antibodies

Smith

Crowe

2015

Microbiol Spectr

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The human hybridoma technique offers an important approach for isolation of human monoclonal antibodies. A diversity of approaches can be used with varying success. Recent technical advances in expanding the starting number of human antigen-specific B cells, improving fusion efficiency, and isolating new myeloma partners and new cell cloning methods have enabled the development of protocols that make the isolation of human monoclonal antibodies from blood samples feasible. Undoubtedly, additional innovations that could improve efficiency are possible. HISTORY OF HYBRIDOMASMonoclonal antibodies (mAbs) have revolutionized the conduct of science since their first description in 1975 (1). The use of these specific reagents also has made possible improved clinical diagnostics in the medical arena, and many antibodies have found their way to clinical use as prophylactic or therapeutic agents. Nevertheless, the potential of mAbs derived specifically from technology based on human hybridomas remains largely unfulfilled. The principal reason for the lack of a large number of hybridoma-derived mAb therapeutics has simply been the technical difficulty in generating stable hybridomas that secrete human mAbs of high affinity and functional activity. This chapter reviews recent efforts to develop and employ novel methods for the efficient generation of human hybridomas secreting human mAbs for clinical use.The principal advantage of the use of human hybridoma technology for mAb generation is that this approach preserves the authentic sequence and pairing of antibody DNA from a natural B cell for the expression of a naturally occurring full-length human mAb. There are significant theoretical advantages for expressing cDNAs encoding authentic heavy and light chains with chains that are paired using the coding sequence as it was generated naturally through B cell selection, class switch, and affinity maturation. No genetic modification of these sequences is required. Since antibody expression is typically very stable in hybridomas, sequence amplification of antibody variable genes is achieved easily if recombinant production or manipulation is desired. The resulting recombinant mAb retains most features of naturally occurring human antibodies, as the clone retains the native amino acid sequence and heavy/light chain pairing. Since the native constant region of the antibody in the original human B cell is retained in the mAb expressed by the resulting hybridoma, the functional properties of the particular Fc region can be studied for Fc-mediated activities, such as antibodydependent cellular cytotoxicity.

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Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors

Cited by 47 publications

References 27 publications

Cross-Protection of Chicken Immunoglobulin Y Antibodies against H5N1 and H1N1 Viruses Passively Administered in Mice

Cross-Protection of Chicken Immunoglobulin Y Antibodies against H5N1 and H1N1 Viruses Passively Administered in Mice

Analysis of Antigenically Important Residues in Human Influenza A Virus in Terms of B-Cell Epitopes

Use of Human Hybridoma Technology To Isolate Human Monoclonal Antibodies

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