H5 N-terminal β sheet promotes oligomerization of H7-HA1 that induces better antibody affinity maturation and enhanced protection against H7N7 and H7N9 viruses compared to inactivated influenza vaccine

Khurana, Surender; Coyle, Elizabeth M.; Verma, Swati; King, Lisa R.; Manischewitz, Jody; Crevar, Corey J.; Carter, Donald M.; Ross, Ted M.; Golding, Hana

doi:10.1016/j.vaccine.2014.09.049

Cited by 25 publications

(25 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The unadjuvanted vaccine generated primarily antibodies targeting the HA2 domain and C-terminus of the HA1 domain, which seems to be mostly buried on the virion spikes and not overlapping with the main protective sites around the receptor binding domain (RBD). This finding was confirmed Please cite this article in press as: Chung when unadjuvanted post-vaccination sera demonstrated comparatively poor binding to properly folded oligomeric H7 HA1 protein (mimicking native spikes) [26], as measured by SPR. This predominant antibody response to HA2 domain and C-terminus of the HA1 domain in the unadjuvanted vaccinees is primarily due to recall of cross reactive antibodies in these adults due to high sequence conservation with the seasonal H3 influenza strains due to prior exposure or vaccination with seasonal influenza (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 69%

See 1 more Smart Citation

ISCOMATRIX™ adjuvant promotes epitope spreading and antibody affinity maturation of influenza A H7N9 virus like particle vaccine that correlate with virus neutralization in humans

Chung¹,

Coyle²,

Jani³

et al. 2015

Vaccine

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 69%

“…The H7 HA1 and HA2 proteins were produced and were properly folded that contained a high percentage of functional oligomers as previously described [26].…”

Section: Microneutralization Assaymentioning

confidence: 99%

ISCOMATRIX™ adjuvant promotes epitope spreading and antibody affinity maturation of influenza A H7N9 virus like particle vaccine that correlate with virus neutralization in humans

Chung¹,

Coyle²,

Jani³

et al. 2015

Vaccine

Self Cite

View full text Add to dashboard Cite

“…H7-HA1 oligomers were produced in E. coli. They were previously shown to be functional by hemagglutination and induction of protective immunity in ferrets (20). In this study, SPR chips coated with either H7-HA1 or H7-HA2 domains were used for analysis of total antibody binding (maximum resonance units [RU]) using 15 individual plasma samples obtained following H7N7 exposure ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Synthetic DNAs encoding HA1 (positions 1 to 320) and HA2 (positions 331 to 540) of H7N7 A/Netherlands/33/03 (identical to HA from A/Netherlands/219/03) were cloned, expressed, and purified as previously described (20). Escherichia coli BL21 cells (Novagen) were used for expression.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Antigenic Fingerprinting of Antibody Response in Humans following Exposure to Highly Pathogenic H7N7 Avian Influenza Virus: Evidence for Anti-PA-X Antibodies

Khurana

Chung

Coyle

et al. 2016

J Virol

Self Cite

View full text Add to dashboard Cite

Infections with H7 highly pathogenic avian influenza (HPAI) viruses remain a major public health concern. Adaptation of lowpathogenic H7N7 to highly pathogenic H7N7 in Europe in 2015 raised further alarm for a potential pandemic. An in-depth understanding of antibody responses to HPAI H7 virus following infection in humans could provide important insight into virus gene expression as well as define key protective and serodiagnostic targets. Here we used whole-genome gene fragment phage display libraries (GFPDLs) expressing peptides of 15 to 350 amino acids across the complete genome of the HPAI H7N7 A/Netherlands/33/03 virus. The hemagglutinin (HA) antibody epitope repertoires of 15 H7N7-exposed humans identified clear differences between individuals with no hemagglutination inhibition (HI) titers (<1:10) and those with HI titers of >1:40. Several potentially protective H7N7 epitopes close to the HA receptor binding domain (RBD) and neuraminidase (NA) catalytic site were identified. Surface plasmon resonance (SPR) analysis identified a strong correlation between HA1 (but not HA2) binding antibodies and H7N7 HI titers. A proportion of HA1 binding in plasma was contributed by IgA antibodies. Antibodies against the N7 neuraminidase were less frequent but targeted sites close to the sialic acid binding site. Importantly, we identified strong antibody reactivity against PA-X, a putative virulence factor, in most H7N7-exposed individuals, providing the first evidence for in vivo expression of PA-X and its recognition by the immune system during human influenza A virus infection. This knowledge can help inform the development and selection of the most effective countermeasures for prophylactic as well as therapeutic treatments of HPAI H7N7 avian influenza virus. IMPORTANCEAn outbreak of pathogenic H7N7 virus occurred in poultry farms in The Netherlands in 2003. Severe outcome included conjunctivitis, influenza-like illness, and one lethal infection. In this study, we investigated convalescent-phase sera from H7N7-exposed individuals by using a whole-genome phage display library (H7N7-GFPDL) to explore the complete repertoire of post-H7N7-exposure antibodies. PA-X is a recently identified influenza virus virulence protein generated by ribosomal frameshifting in segment 3 of influenza virus coding for PA. However, PA-X expression during influenza virus infection in humans is unknown. We identified strong antibody reactivity against PA-X in most H7N7-exposed individuals (but not in unexposed adults), providing the first evidence for in vivo expression of PA-X and its recognition by the immune system during human infection with pathogenic H7N7 avian influenza virus.A vian influenza viruses (AIVs) are mostly restricted to aquatic birds. On occasion, they acquire the capacity to directly infect the respiratory tract of poultry and mammals. Such cross-species transmission often results in a large number of sick birds (chickens and turkeys), as was reported for H7N1 viruses in Italy in 1999, H7N3 viruses in Canada in 2...

show abstract

Recombinant hemagglutinin proteins formulated in a novel PELC/CpG adjuvant for H7N9 subunit vaccine development

et al. 2017

View full text Add to dashboard Cite

H5 N-terminal β sheet promotes oligomerization of H7-HA1 that induces better antibody affinity maturation and enhanced protection against H7N7 and H7N9 viruses compared to inactivated influenza vaccine

Cited by 25 publications

References 20 publications

ISCOMATRIX™ adjuvant promotes epitope spreading and antibody affinity maturation of influenza A H7N9 virus like particle vaccine that correlate with virus neutralization in humans

ISCOMATRIX™ adjuvant promotes epitope spreading and antibody affinity maturation of influenza A H7N9 virus like particle vaccine that correlate with virus neutralization in humans

Antigenic Fingerprinting of Antibody Response in Humans following Exposure to Highly Pathogenic H7N7 Avian Influenza Virus: Evidence for Anti-PA-X Antibodies

Recombinant hemagglutinin proteins formulated in a novel PELC/CpG adjuvant for H7N9 subunit vaccine development

Contact Info

Product

Resources

About