Amino acid sequence identity between the HA1 of influenza A (H3N2) viruses grown in mammalian and primary chick kidney cells

Katz, Jacqueline M.; Webster, Robert G.

doi:10.1099/0022-1317-73-5-1159

Cited by 56 publications

(38 citation statements)

References 22 publications

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“…The speed limitation of live virus-based vaccine production is exacerbated in a case of an emerging pandemic when a new virus strain appears rather suddenly and unpredictably. Additionally, the process of virus passage results in mutations in the vaccine viruses, leading to a mismatch between the vaccine composition and the dangerous strains it is intended to protect against (Katz and Webster 1992). Due to the slow vaccine manufacturing and mismatches between the vaccine and circulating strains, widespread and timely prophylaxis through rapid manufacturing and deployment of effective vaccine remains a significant unsolved challenge for influenza.…”

Section: Pandemic Influenza a And Current Influenza Vaccine Manufactumentioning

confidence: 99%

“…The carboxyl terminus of HA2 contains the hydrophobic transmembrane sequence and a terminal cytoplasmic anchor sequence where palmitate is connected (Figure 2-3D). The globular region is solely composed of HA1, and it contains most of the antigenic sites of the molecule as well as the receptor-binding site (Katz andWebster 1992, Wilson et al 1981). , the receptor-binding site, carbohydrate attachment sites (CHO) and its position on the membrane; (B) The eight-stranded β-sheet and looped-out region in the globular domain; (C) HA2, showing two α-helices (cylinders).…”

Section: Haemagglutinin (Ha)mentioning

confidence: 99%

“…Third, eggs can also potentially select for variants that grow well in the environment used during the adaptation process (Kistner et al 1998, Ulmer et al 2006. Nucleotide sequencing has indicated that the HAs of influenza A strains grown in the egg have a single base substitution and subsequently a single amino change (Katz andWebster 1992, Robertson 1993). Such amino acid substitutions can result in antigenic mismatch between vaccine strains and circulating strains (Tree et al 2001).…”

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Engineering of virus-like particles for alternative vaccine candidate targeting a hypervariable peptide antigen element

Anggraeni¹

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A promising alternative to replace the current egg-or cell culture-based technology for vaccine production from live viruses is virus-like particle (VLP) technology based on a microbial platform. VLPs are macromolecular assemblies of viral capsid proteins, which have been shown to tolerate insertion of antigen modules via genetic recombinant technology, yielding modular VLPs. Many studies on modular VLPs presume that when a peptide antigen element is taken out from the intact proteins and then modularised on VLPs, it is unable to fold into its native structure. However, until now, presentation of a peptide antigen element on a VLP and the impact of the display strategy to present the antigen element on the quality of the resulting antibodies (i.e. the ability of the antibodies to recognise the intact protein) are not fully understood. This thesis aims to understand the underlying fundamentals regarding modularisation of peptide antigen elements on VLPs for induction of high-quality antibodies. A hypervariable receptor-binding domain, Helix 190 (H190), from the hemagglutinin protein of influenza A virus was used as a model for modularisation on VLPs from murine polyomavirus (MuPyV) VP1 protein. Four major findings are presented. Firstly, two display strategies, i.e. arraying of H190 in tandem repeats and the use of helix promoter elements, were shown to display H190 in its immunogenic form equally. However, modularisation using tandem repeat display induced antibodies of a higher quality than modularisation using helix promoter elements.Secondly, the quality of antibodies induced by the tandem repeat display bearing two copies of H190 was optimum, thus no significant improvement was observed following the use of adjuvant or increasing the copy number of H190. Additionally, the increase in the copy number of H190 was shown to reduce the assembly capability and solubility of modular VP1 in an environment that was optimised for wild-type VP1. Thirdly, this thesis shows the novel finding in the use of flanking ionic elements to stabilise VLP precursors, termed as capsomeres, bearing two copies of H190 containing a hydrophobic stretch, which caused aggregation. Fourthly, the first steps towards obtaining the atomic crystal structure of presented H190 on a modular protein were performed, i.e. a mild and satisfactory laboratory process was developed to achieve high-purity modular VP1 capsomeres, unattainable using previously established expression and purification process of wild-type MuPyV VP1. This thesis shows a step forward towards understanding the presentation of a peptide antigen element on a VLP that enables induction of highquality antibodies, and towards VLP engineering to manipulate the aggregation and solubility of modular VP1. VLP technology based on a microbial platform presented here is iii a potentially safe and effective alternative vaccine candidate that targets a hypervariable peptide antigen element. The speed of the microbial platform allows a rapid response to the hypervariability of the pe...

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Section: Pandemic Influenza a And Current Influenza Vaccine Manufactumentioning

confidence: 99%

Section: Haemagglutinin (Ha)mentioning

confidence: 99%

mentioning

confidence: 99%

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Engineering of virus-like particles for alternative vaccine candidate targeting a hypervariable peptide antigen element

Anggraeni¹

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“…Fourth, influenza viruses appear to mutate more frequently around the receptor binding site and be selected when passaged in ECE, compared to passage in cells cultured in vitro. [38][39][40][41][42][43] This could potentially affect vaccine efficacy, as has been seen in animal models. 44,45 Moreover, eggbased antigens may elicit weaker immunogenicity compared to cell culture-derived antigens.…”

Section: Introductionmentioning

confidence: 99%

Cell culture-based influenza vaccines: A necessary and indispensable investment for the future

Hegde

2015

Human Vaccines & Immunotherapeutics

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“…The other minor variant, Sw/IA/88, contained four point mutations which resulted in four amino acid substitutions compared with the virus passaged in embryonated eggs, suggesting the selection of a variant with a growth advantage. Other studies have shown that passage of human H 1 (Robertson et al, 1987Oxford et al, 1991) and H3 influenza viruses (Katz & Webster, 1992) in embryonated eggs can select for virus subpopulations. Also, the Sw/IA/88 virus in the pig lungs had only one amino acid substitution (146, Asn to Ser) compared with Sw/IN/88.…”

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confidence: 99%

Antigenic and genetic conservation of the haemagglutinin in H1N1 swine influenza viruses

Noble

McGregor²,

Wentworth³

et al. 1993

Journal of General Virology

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We examined the level of antigenic conservation amongst the haemagglutinins (HAs) of H1 swine influenza viruses, recently isolated from a wide geographical area, in haemagglutination inhibition assays against a panel of four monoclonal antibodies (MAbs). We found a high degree of conservation with a dominant variant (52 of 54 isolates) that reacted with all MAbs. Only two minor variants, each failing to react with one MAb, were found. Using a one-step PCR technique followed by direct sequencing of the products, we examined the HA1 region of the HA RNA of two representative dominant variants. We found no amino acid substitutions relative to a reference strain. The sequences of the HA1 RNA of the two minor variants isolated here and of two other minor variants defined previously were also determined. Each contained inferred amino acid substitutions, all located at different positions on the HA. Finally, we sequenced HA1 RNA obtained from the original pig lung suspensions from which the two dominant and two minor variants had been isolated. Three of the parent viruses were identical to their progeny in eggs whereas the fourth parent virus contained four amino acid differences from its progeny.Previous studies have investigated the haemagglutinin (HA) of swine influenza viruses isolated over a 24 year period using haemagglutination inhibition (HI) assays with a panel of monoclonal antibodies (MAbs) that identified three antigenic sites. These antigenic sites had remained unchanged over 24 years and only one antigenic variant was detected (Sheerar et al., 1989;Luoh et al., 1992). Since these studies had focused on viruses within an enzootic area of Wisconsin, U.S.A., we wanted to know whether or not more recent swine viruses isolated over a wider geographical area, i.e. epizootic viruses, exhibited the same degree of antigenic conservation. Using PCR directly on viral RNA (vRNA) and direct sequencing of the cDNA products we also studied the level of genetic conservation of RNA encoding the HA of these viruses.A total of 110 pig lung tissue samples previously diagnosed as influenza virus-positive by examination with fluorescent antibody were kindly provided for this study by Dr Mary Lynn Vickers of the Animal Health Laboratory, University of South Dakota. These were macerated by a stomacher (Tekmar) in Hanks' buffered salt solution, clarified by low-speed centrifugation and supernatants were then inoculated into the allantoic cavity of 10-day-old embryonated chicken eggs and incubated at 35 °C for 72 h. Virus was isolated from 54 samples, from pigs from Kentucky (three samples), Iowa (13), Nebraska (seven), South Dakota (18), North Dakota (one), Minnesota (six), Illinois (one) and Wisconsin (five). Isolates were screened with an HI assay against the panel of MAbs described previously (Sheerar et al., 1989). ELISAs and virus neutralization assays were performed as described (Sheerar et al., 1989). All isolates were H1N1.RNA was extracted either directly from pig lung suspensions or from pelleted virus using 4 N-guanidi...

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Amino acid sequence identity between the HA1 of influenza A (H3N2) viruses grown in mammalian and primary chick kidney cells

Cited by 56 publications

References 22 publications

Engineering of virus-like particles for alternative vaccine candidate targeting a hypervariable peptide antigen element

Engineering of virus-like particles for alternative vaccine candidate targeting a hypervariable peptide antigen element

Cell culture-based influenza vaccines: A necessary and indispensable investment for the future

Antigenic and genetic conservation of the haemagglutinin in H1N1 swine influenza viruses

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