Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets

Khurana, Surender; Suguitan, Amorsolo L.; Rivera, Yonaira M.; Simmons, Cameron P.; Lanzavecchia, Antonio; Sallusto, Federica; Manischewitz, Jody; King, Lisa R.; Subbarao, Kanta; Golding, Hana

doi:10.1371/journal.pmed.1000049

Cited by 159 publications

(215 citation statements)

References 36 publications

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“…On the other hand, we have demonstrated here and in previous studies that bacterially expressed unglycosylated HA1 (and HA0) can be purified as properly folded proteins, as determined by CD spectra analysis and binding to conformation-dependent neutralizing antibodies (12,13), in agreement with the findings in another recent study (1).…”

Section: Discussionsupporting

confidence: 92%

“…To better understand the role of HA1 structure-function and its effect on generating protective immunity after immunization, we expressed a series of H5N1-derived HA1 proteins with N-and C-terminal deletions and evaluated their ability to form oligomers and to agglutinate RBCs. The intact H5N1 HA1 and a series of truncated proteins were expressed in E. coli and isolated from inclusion bodies by denaturation and slow renaturation under controlled redox refolding conditions as previously described (11,12). The His 6 -tagged fusion proteins were purified using Ni-NTA chromatography to Ͼ95% purity ( Agglutination of red cells is a surrogate for the binding of influenza virus to its sialic acid receptors.…”

Section: Resultsmentioning

confidence: 99%

“…Most of the influenza virus protective antigenic sites are conformation dependent and map primarily to the HA1 globular head (22,30). Previously, we used H5N1 whole-genome phage display libraries to map the antibody repertoires following human infection with HP H5N1 (A/Vietnam/1203/2004) AIV, as well as in post-H5N1 vaccination sera (11,12). We have identified large HA1 fragments, encompassing the receptor-binding domain (RBD), that bound broadly neutralizing human monoclonal antibodies and polyclonal sera from H5N1 recovered individuals.…”

mentioning

confidence: 99%

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Bacterial HA1 Vaccine against Pandemic H5N1 Influenza Virus: Evidence of Oligomerization, Hemagglutination, and Cross-Protective Immunity in Ferrets

Khurana

Verma

et al. 2011

J Virol

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Bacterial HA1 Vaccine against Pandemic H5N1 Influenza Virus: Evidence of Oligomerization, Hemagglutination, and Cross-Protective Immunity in Ferrets

Khurana

Verma

et al. 2011

J Virol

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“…Hence, these peptides may also evoke a B cell response against the influenza virus. This is in accordance with an earlier study in which one of our identified peptides (LQAYQKRMGVQMQR) forms part of the B cell epitope, reported to induce IgG production in patients who have just recovered from H5N1 infection (25).…”

Section: Discussionsupporting

confidence: 93%

Identification of Conserved Peptides Comprising Multiple T Cell Epitopes of Matrix 1 Protein in H1N1 Influenza Virus

Lohia

Baranwal

2015

Viral Immunology

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Cell mediated immune response plays a key role in combating viral infection and thus identification of new vaccine targets manifesting T cell mediated response may serve as an ideal approach for influenza vaccine. The present study involves the application of an immunoinformatics-based consensus approach for epitope prediction (three epitope prediction tools each for CD4+ and CD8+ T cell epitopes) and molecular docking to identify peptide sequences containing T cell epitopes using the conserved sequences from all the Matrix 1 protein sequences of H1N1 virus available until April 2015. Three peptides comprising CD4+ and CD8+ T cell epitopes were obtained, which were not exactly reported in earlier studies. Population coverage study of these multiepitope peptides revealed that they are capable of inducing a potent immune response belonging to individuals from different populations and ethnicity distributed around the globe. Conservation study with other subtypes of influenza virus infecting humans (H2N2, H5N1, H7N9, and H3N2) revealed that these three peptides were conserved (>90%), with 100% identity in most of these strains. Hence, these peptides can impart immunity against H1N1 as well as other subtypes of influenza virus. A molecular docking study of the predicted peptides with class I and II human leukocyte antigen (HLA) molecules has shown that the majority of them have comparable binding energies to that of native peptides. Hence, these peptides from Matrix 1 protein of H1N1 appear to be promising candidates for universal vaccine design.

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“…While the dominant neutralizing epitopes are found in the HA, antibodies to the NA and M2 ectodomain also have protective activity. A recent study using whole genome fragment phage display libraries has shown that this strategy can be used to identify human antibody-binding epitopes on all virus proteins so as to compile a systematic analysis of antibody-binding epitopes for a given virus [45].…”

Section: Antibody-mediated Protectionmentioning

confidence: 99%

A novel H1N1 virus causes the first pandemic of the 21^st century

Peiris

Yen

2009

Eur J Immunol

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A novel H1N1 virus of swine origin (H1N1v ) is currently spreading in humans, giving rise to the first pandemic in 40 years. The disease is of moderate severity but has notable differences from seasonal influenza. In contrast to seasonal influenza, those over 60 years are relatively spared, a likely consequence of the presence of H1N1v crossneutralizing antibody in this age group. Most patients appear to have mild influenza-like illness and many of the complications leading to hospitalization and mortality occur in those with underlying disease conditions or pregnancy. Studies in animal models suggest that the novel H1N1v pandemic virus causes a more severe illness and appears to have a greater predilection for the alveolar epithelium than seasonal influenza viruses. As there are as yet little data on the pathogenesis and immunology of H1N1v infection in humans, we have reviewed relevant data from past pandemics, from seasonal influenza and avian influenza H5N1 to highlight key issues pertaining to pathogenesis and immunology.Key words: H1N1 . Immunology . Influenza . Pandemic . Pathogenesis Introduction A novel H1N1 virus originating in swine recently emerged as the first influenza pandemic of the 21 st century [1]. As the 20 th century saw three influenza pandemics, in 1918 (H1N1), 1957 (H2N2) and 1968 (H3N2), and the historical record indicates that there were approximately three to four influenza-like pandemics every century, going back to 1500 AD [2], the emergence of a pandemic 40 years after the last in 1968 was hardly a surprise. Its nature and origins however, were unexpected. This review summarizes the emergence of this pandemic, clinical features of the disease and its pathogenesis, and also highlights the key questions for immunological research. The virus and the birth of pandemicsPandemic influenza is caused by type A influenza viruses and these are single-stranded RNA viruses with an eight-segmented genome. Type A influenza viruses are subtyped on the basis of antigenic relationships of the virus surface glycoproteins, the HA and neuraminidase (NA), into 16 HA and 9 NA subtypes. The HA and NA are the key antigens to which protective antibody responses are directed and there is minimal serological crossprotection across HA subtypes. All 16 HA and 9 NA subtypes are present in the aquatic avian reservoir while a more restricted range of subtypes are endemic in other species such as pigs (H1, H3) and horses (H3, H7). Pandemics were believed to arise when a virus with a novel HA subtype (sometimes together with a novel NA) adapts to efficient transmission in humans [3]. The recent H1N1 pandemic arose from a swine H1N1 virus adapting to human transmission without genetic reassortment with current 2946Review human influenza viruses, i.e. all eight gene segments of the animal virus adapted to human transmission [4,5]. Aspects of the evolution of viruses in pigs and how these contributed to the genesis of the current pandemic virus have been reviewed elsewhere [6].Since previous pandemics arose from a su...

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Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets

Abstract: Using whole-genome-fragment phage display libraries, Hana Golding and colleagues identify the viral epitopes recognized by serum antibodies in humans who have recovered from infection with H5N1 avian influenza.

Cited by 159 publications

References 36 publications

Bacterial HA1 Vaccine against Pandemic H5N1 Influenza Virus: Evidence of Oligomerization, Hemagglutination, and Cross-Protective Immunity in Ferrets

Bacterial HA1 Vaccine against Pandemic H5N1 Influenza Virus: Evidence of Oligomerization, Hemagglutination, and Cross-Protective Immunity in Ferrets

Identification of Conserved Peptides Comprising Multiple T Cell Epitopes of Matrix 1 Protein in H1N1 Influenza Virus

A novel H1N1 virus causes the first pandemic of the 21^st century

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Antigenic Fingerprinting of H5N1 Avian Influenza Using Convalescent Sera and Monoclonal Antibodies Reveals Potential Vaccine and Diagnostic Targets

Abstract: Using whole-genome-fragment phage display libraries, Hana Golding and colleagues identify the viral epitopes recognized by serum antibodies in humans who have recovered from infection with H5N1 avian influenza.

Cited by 159 publications

References 36 publications

Bacterial HA1 Vaccine against Pandemic H5N1 Influenza Virus: Evidence of Oligomerization, Hemagglutination, and Cross-Protective Immunity in Ferrets

Bacterial HA1 Vaccine against Pandemic H5N1 Influenza Virus: Evidence of Oligomerization, Hemagglutination, and Cross-Protective Immunity in Ferrets

Identification of Conserved Peptides Comprising Multiple T Cell Epitopes of Matrix 1 Protein in H1N1 Influenza Virus

A novel H1N1 virus causes the first pandemic of the 21st century

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A novel H1N1 virus causes the first pandemic of the 21^st century