Abstract:
:Each influenza season, a set of wild-type viruses, representing one H1N1, one H3N2, and one to two influenza B isolates, are selected for inclusion in the annual seasonal influenza vaccine. In order to develop broadly reactive subtype-specific influenza vaccines, a methodology called computationally optimized broadly reactive antigens (COBRA) was used to design novel hemagglutinin (HA) vaccine immunogens. COBRA technology was effectively used to design HA immunogens that elicited antibodies that neutralized H5N1 and H1N1 isolates. In this report, the development and characterization of 17 prototype H3N2 COBRA HA proteins were screened in mice and ferrets for the elicitation of antibodies with HA inhibition (HAI) activity against human seasonal H3N2 viruses that were isolated over the last 48 years. The most effective COBRA HA vaccine regimens elicited antibodies with broader HAI activity against a panel of H3N2 viruses than wild-type H3 HA vaccines. The top leading COBRA HA candidates were tested against cocirculating variants. These variants were not efficiently detected by antibodies elicited by the wild-type HA from viruses selected as the vaccine candidates. The T-11 COBRA HA vaccine elicited antibodies with HAI and neutralization activity against all cocirculating variants from 2004 to 2007. This is the first report demonstrating broader breadth of vaccine-induced antibodies against cocirculating H3N2 strains compared to the wild-type HA antigens that were represented in commercial influenza vaccines.IMPORTANCE There is a need for an improved influenza vaccine that elicits immune responses that recognize a broader number of influenza virus strains to prevent infection and transmission. Using the COBRA approach, a set of vaccines against influenza viruses in the H3N2 subtype was tested for the ability to elicit antibodies that neutralize virus infection against not only historical vaccine strains of H3N2 but also a set of cocirculating variants that circulated between 2004 and 2007. Three of the H3N2 COBRA vaccines recognized all of the cocirculating strains during this era, but the chosen wild-type vaccine strains were not able to elicit antibodies with HAI activity against these cocirculating strains. Therefore, the COBRA vaccines have the ability to elicit protective antibodies against not only the dominant vaccine strains but also minor circulating strains that can evolve into the dominant vaccine strains in the future.
journal_name
J Viroljournal_title
Journal of virologyauthors
Wong TM,Allen JD,Bebin-Blackwell AG,Carter DM,Alefantis T,DiNapoli J,Kleanthous H,Ross TMdoi
10.1128/JVI.01581-17subject
Has Abstractpub_date
2017-11-30 00:00:00issue
24eissn
0022-538Xissn
1098-5514pii
JVI.01581-17journal_volume
91pub_type
杂志文章abstract::The vaccinia virus A16L open reading frame encodes a 378-amino-acid protein with a predicted C-terminal transmembrane domain and 20 invariant cysteine residues that is conserved in all sequenced members of the poxvirus family. The A16 protein was expressed late in infection and incorporated into intracellular virus pa...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.80.1.51-61.2006
更新日期:2006-01-01 00:00:00
abstract::Rabies continues to present a public health threat in most countries of the world. The most efficient way to prevent and control rabies is to implement vaccination programs for domestic animals. However, traditional inactivated vaccines used in animals are costly and have relatively low efficiency, which impedes their...
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doi:10.1128/JVI.02324-16
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abstract::Adenovirus deletion mutants were studied to examine the influence of the 5' untranslated sequence on the translation of early region 1A mRNAs. Alterations of the 5' untranslated sequence, including complete deletion of the wild-type 5' untranslated sequence, did not significantly affect the rate of translation. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.51.3.884-888.1984
更新日期:1984-09-01 00:00:00
abstract::Lymphocyte antigen 6E (LY6E) is a GPI-anchored, interferon-inducible protein that has been shown to modulate viral infection in a cell type-dependent manner. Our recent work showed that LY6E promotes HIV-1 infection in some high-CD4-expressing cells, including human peripheral blood mononuclear cells (PBMCs) and the S...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01866-18
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abstract::DNA replication intermediates of three plasmids containing all or part of a modified Epstein-Barr virus cis-acting plasmid maintenance region (oriP) were examined to further investigate oriP function. Replication intermediates were analyzed in vivo and in vitro by neutral-neutral two-dimensional gel electrophoresis. T...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.67.3.1739-1745.1993
更新日期:1993-03-01 00:00:00
abstract::Glycoprotein D (gD) interacts with two alternative protein receptors, nectin1 and HveA, to mediate herpes simplex virus (HSV) entry into cells. Fusion of the envelope with the plasma membrane requires, in addition to gD, glycoproteins gB, gH, and gL. Coexpression of the four glycoproteins (gD, gB, gH, and gL) promotes...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.6.3759-3767.2003
更新日期:2003-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.9.4874-4881.1991
更新日期:1991-09-01 00:00:00
abstract:UNLABELLED:To investigate the molecular mechanism(s) by which herpes simplex virus 1 (HSV-1) tegument protein UL51 promotes viral replication, we screened for viral proteins that interact with UL51 in infected cells. Affinity purification of tagged UL51 in HSV-1-infected Vero cells was coupled with immunoblotting of th...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01258-16
更新日期:2016-09-12 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00998-10
更新日期:2011-01-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01906-14
更新日期:2014-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01702-15
更新日期:2015-11-01 00:00:00
abstract::A new subgroup of avian leukosis virus (ALV) that includes a unique env gene, designated J, was identified recently in England. Sequence analysis of prototype English isolate HPRS-103 revealed several other unique genetic characteristics of this strain and provided information that it arose by recombination between ex...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.12.10301-10304.1998
更新日期:1998-12-01 00:00:00
abstract::Human herpesvirus 8 (HHV8) open reading frame (ORF) 21 is predicted to encode a protein similar to the thymidine kinase (TK) enzyme of other herpesviruses. Expressed in mammalian cells, ORF 21 was found to have low TK activity, based on poor growth in media containing hypoxanthine-aminopterin-thymidine (HAT) and low i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.2.684-692.2000
更新日期:2000-01-01 00:00:00
abstract::A study of virus-specific protein synthesis in infectious pancreatic necrosis virus-infected RTG-2 cells was undertaken to find a relationship between the coding capacity of virus genome (two segments of double-stranded RNA of 2.5 X10(6) and 2.3 X 10(6) molecular weight) and the sizes and relative amounts of polypepti...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.21.1.242-258.1977
更新日期:1977-01-01 00:00:00
abstract:UNLABELLED:Marek's disease virus (MDV), an alphaherpesvirus, is the causative agent of a lethal disease in chickens characterized by generalized nerve inflammation and rapid lymphoma development. The extensive colinearity of the MDV genome with those of related herpesviruses has eased functional characterization of man...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02687-14
更新日期:2015-01-15 00:00:00
abstract::A molecular clone of mouse-neuroadapted yellow fever 17D virus (SPYF-MN) was used to identify critical determinants of viral neuroinvasiveness in a SCID mouse model. Virus derived from this clone differs from nonneuroinvasive YF5.2iv virus at 29 nucleotide positions, encoding 13 predicted amino acid substitutions and ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.22.12232-12242.2003
更新日期:2003-11-01 00:00:00
abstract::The production and selection of infectious vaccinia virus recombinants expressing foreign genes was facilitated by the construction of plasmid vectors. These vectors contain all or part of the vaccinia virus thymidine kinase (TK) gene interrupted by multiple unique restriction endonuclease sites placed adjacent to the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.49.3.857-864.1984
更新日期:1984-03-01 00:00:00
abstract::A soluble system was developed that could support DNA replication in simian virus 40 (SV40) chromosomes. DNA synthesis in this system required the presence of purified SV40 large tumor antigen, SV40 chromosomes prepared from virus-infected monkey cells, a crude extract from HeLa cells, and several low-molecular-weight...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.10.4820-4829.1990
更新日期:1990-10-01 00:00:00
abstract:UNLABELLED:In the last decade, novel tick-borne pathogenic phleboviruses in the family Bunyaviridae, all closely related to Uukuniemi virus (UUKV), have emerged on different continents. To reproduce the tick-mammal switch in vitro, we first established a reverse genetics system to rescue UUKV with a genome close to tha...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00095-16
更新日期:2016-07-11 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.8.3470-3477.2000
更新日期:2000-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.28.1.154-170.1978
更新日期:1978-10-01 00:00:00
abstract::The sequence of the S RNA of La Crosse bunyavirus was deduced from analyses of DNA copies cloned in the Escherichia coli plasmid pBR322. The S RNA is 984 nucleotides in length, has a base ratio of 31.8% U, 27.0% A, 23.2% C, and 18.0% G, and codes for two distinct gene products that are read from overlapping reading fr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.45.3.1155-1158.1983
更新日期:1983-03-01 00:00:00
abstract::Purified Friend viruses obtained from chronically infected tissue cultures were studied under the electron microscope in an effort to correlate the fine structure of the particles to their leukemogenic activity under varied experimental conditions, i.e., temperature treatments and exposure to Tween 80, amyl acetate, o...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.2.4.365-375.1968
更新日期:1968-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03426-12
更新日期:2013-05-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02778-13
更新日期:2014-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.3.2022-2026.1996
更新日期:1996-03-01 00:00:00
abstract::Epstein-Barr virus (EBV)-induced B-cell growth transformation, a central feature of the virus' strategy for colonizing the human B-cell system, requires full virus latent gene expression and is initiated by transcription from the viral promoter Wp. Interestingly, when EBV accesses other cell types, this growth-transfo...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.22.10458-10467.2000
更新日期:2000-11-01 00:00:00
abstract::A 4,500-bp BamHI fragment, located within the HindIII A segment of the vaccinia virus genome, was found to contain eight potential coding regions for polypeptides of 78 to 346 amino acids. The open reading frames with 133, 346, and 125 codons were homologous to profilin (an actin-binding protein), 3-beta-hydroxysteroi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.9.4598-4608.1991
更新日期:1991-09-01 00:00:00
abstract::Retrovirus replication requires the production of both spliced and unspliced viral RNA from a single RNA transcript. In contrast, cellular RNA precursors with introns almost completely spliced. The cis elements and virus-coded trans factors which determine the extent to which Rous sarcoma virus RNA is spliced to src m...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.63.4.1669-1676.1989
更新日期:1989-04-01 00:00:00
abstract::Bovine herpesvirus 1 (BoHV-1) is an alphaherpesvirus that causes disease in cattle populations worldwide. Sphingomyelin (SM) is the most abundant sphingolipid in the mammalian cell membrane, where it preferentially associates with cholesterol to form lipid raft domains. SM is a substrate for the lysosome-resident enzy...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01547-18
更新日期:2019-02-19 00:00:00