Abstract:
:The vast majority of people already have preexisting immune responses to influenza viruses from one or more subtypes. However, almost all preclinical studies evaluate new influenza vaccine candidates in immunologically naive animals. Recently, our group demonstrated that priming naive ferrets with broadly reactive H1 COBRA HA-based vaccines boosted preexisting antibodies induced by wild-type H1N1 virus infections. These H1 COBRA hemagglutinin (HA) antigens induced antibodies with HAI activity against multiple antigenically different H1N1 viral variants. In this study, ferrets, preimmune to historical H3N2 viruses, were vaccinated with virus-like particle (VLP) vaccines expressing either an HA from a wild-type H3 influenza virus or a COBRA H3 HA antigen (T6, T7, T10, or T11). The elicited antisera had the ability to neutralize virus infection against either a panel of viruses representing vaccine strains selected by the World Health Organization or a set of viral variants that cocirculated during the same time period. Preimmune animals vaccinated with H3 COBRA T10 HA antigen elicited sera with higher hemagglutination inhibition (HAI) antibody titers than antisera elicited by VLP vaccines with wild-type HA VLPs in preimmune ferrets. However, while the T11 COBRA vaccine did not elicit HAI activity, the elicited antibodies did neutralize antigenically distinct H3N2 influenza viruses. Overall, H3 COBRA-based HA vaccines were able to neutralize both historical H3 and contemporary, as well as future, H3N2 viruses with higher titers than vaccines with wild-type H3 HA antigens. This is the first report demonstrating the effectiveness of a broadly reactive H3N3 vaccine in a preimmune ferret model.IMPORTANCE After exposure to influenza virus, the host generates neutralizing anti-hemagglutinin (anti-HA) antibodies against that specific infecting influenza strain. These antibodies can also neutralize some, but not all, cocirculating strains. The goal of next-generation influenza vaccines, such as HA head-based COBRA, is to stimulate broadly protective neutralizing antibodies against all strains circulating within a subtype, in particular those that persist over multiple influenza seasons, without requiring an update to the vaccine. To mimic the human condition, COBRA HA virus-like particle vaccines were tested in ferrets that were previously exposed to historical H3N2 influenza viruses. In this model, these vaccines elicited broadly protective antibodies that neutralized cocirculating H3N2 influenza viruses isolated over a 20-year period. This is the first study to show the effectiveness of H3N3 COBRA HA vaccines in a host with preexisting immunity to influenza.
journal_name
J Viroljournal_title
Journal of virologyauthors
Allen JD,Jang H,DiNapoli J,Kleanthous H,Ross TMdoi
10.1128/JVI.00946-18subject
Has Abstractpub_date
2019-01-17 00:00:00issue
3eissn
0022-538Xissn
1098-5514pii
JVI.00946-18journal_volume
93pub_type
杂志文章abstract::JC virus (JCV), along with other members of the polyomavirus family, encodes a class of highly conserved proteins, T antigens, that are capable of inducing aneuploidy in cultured cells. We have previously isolated T-antigen DNA variants of JCV from both colon cancer tissues and the corresponding nonneoplastic gastroin...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.4.1996-2001.2001
更新日期:2001-02-01 00:00:00
abstract::A new purification procedure was adopted for Eastern equine encephalitis virus which does not subject the virus to pelleting at any stage. Three- to 4-liter volumes were passed through a diethylaminoethyl cellulose column. The virus-containing fractions were banded on a sucrose cushion and finally concentrated in an i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.7.2.233-240.1971
更新日期:1971-02-01 00:00:00
abstract::We measured the quantity of plasma feline immunodeficiency virus (FIV) RNA using a real-time sequence detecting system. Plasma viral RNA load was shown to correlate with the clinical stage, survival time, and disease progression in naturally FIV-infected cats. The present study indicates that the plasma viral RNA load...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.19.10079-10083.2002
更新日期:2002-10-01 00:00:00
abstract::Interactions between viruses and the host antibody immune response are critical in the development and control of disease, and antibodies are also known to interfere with the efficacy of viral vector-based gene delivery. The adeno-associated viruses (AAVs) being developed as vectors for corrective human gene delivery ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00622-13
更新日期:2013-08-01 00:00:00
abstract::Electron micrographic studies of neuronal axons have produced contradictory conclusions on how alphaherpesviruses are transported from neuron cell bodies to axon termini. Some reports have described unenveloped capsids transported on axonal microtubules with separate transport of viral glycoproteins within membrane ve...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01107-06
更新日期:2006-11-01 00:00:00
abstract::Infections of fungi by mycoviruses are often symptomless but sometimes also fatal, as they perturb sporulation, growth, and, if applicable, virulence of the fungal host. Hypovirulence-inducing mycoviruses, therefore, represent a powerful means to defeat fungal epidemics on crop plants. Infection with Fusarium graminea...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00326-18
更新日期:2018-08-16 00:00:00
abstract::Human cytomegalovirus (HCMV) has evolved multiple strategies for suppression of the antiviral response of the infected cell. DNA array technology has revealed that HCMV clearly regulates host gene expression during the course of a productive infection by enhancing, sustaining, or suppressing steady-state levels of cel...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.1.472-485.2005
更新日期:2005-01-01 00:00:00
abstract::Like almost all of the positive-strand RNA viruses, hepatitis C virus (HCV) induces host intracellular membrane modification to form the membrane-bound viral replication complex (RC), within which viral replicases amplify the viral RNA genome. Despite accumulated information about how HCV co-opts host factors for vira...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01140-16
更新日期:2016-10-14 00:00:00
abstract::Herpes simplex virus establishes latent infections in the nuclei of sensory neurons. These infections are characterized by the abundant expression of a series of 5' coterminal transcripts termed the latency-associated transcripts (LATs). Available evidence indicates that LAT expression is specifically regulated in lat...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.11.7424-7432.1996
更新日期:1996-11-01 00:00:00
abstract::Rodent fibroblasts infected with the ts371 Kirsten murine sarcoma virus (KiMuSV) are temperature sensitive for the maintenance of transformation because of the production of an abnormal p21 protein. We cloned the ts371 KiMuSV provirus from the genome of a conditionally transformed nonproducer cell line, ts371 KiMuSV N...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.60.2.782-786.1986
更新日期:1986-11-01 00:00:00
abstract::Since most human immunodeficiency virus (HIV) infections are initiated following mucosal exposure to the virus, the anatomic containment or abortion of an HIV infection is likely to require vaccine-elicited cellular immune responses in those mucosal sites. Studying vaccine-elicited mucosal immune responses has been pr...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.22.11484-11490.2002
更新日期:2002-11-01 00:00:00
abstract::Genetic variation of the more complex retroviruses in the human T-cell leukemia virus/bovine leukemia virus (HTLV/BLV) group is less than in some other retroviral genera. To test whether reverse transcription of HTLV/BLV group members is less error prone than that of members of other groups, we developed an assay for ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.1.494-499.1994
更新日期:1994-01-01 00:00:00
abstract::Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Nairovirus of the family Bunyaviridae, causes severe disease with high rates of mortality in humans. The CCHFV M RNA segment encodes the virus glycoproteins G(N) and G(C). To understand the processing and intracellular localization of the CCHFV glyco...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.10.6152-6161.2005
更新日期:2005-05-01 00:00:00
abstract::With the aid of three monoclonal antibodies (MAbs), a glycoprotein specifically localized to the outer envelope of vaccinia virus was shown to be encoded by the A33R gene. These MAbs reacted with a glycosylated protein that migrated as 23- to 28-kDa and 55-kDa species under reducing and nonreducing conditions, respect...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.6.3753-3762.1996
更新日期:1996-06-01 00:00:00
abstract::The simian B-lymphotropic papovavirus (LPV) encodes a large tumor antigen (T antigen) which is 45% identical to both the simian virus 40 (SV40) and the polyomavirus (PyV) large T antigens. In transgenic mice, the transforming properties of the LPV T antigen are similar to those of the SV40 T antigen. However, little i...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.10.5417-5424.1991
更新日期:1991-10-01 00:00:00
abstract::Since dendritic cells may play a key role in defense against influenza virus infection, we examined the effects of recombinant hemagglutinin (HA) proteins derived from mouse-adapted H1N1 (A/WSN/1933), swine-origin 2009 pandemic H1N1 (A/Texas/05/2009), and highly pathogenic avian influenza H5N1 (A/Thailand/KAN-1/2004) ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01316-10
更新日期:2010-11-01 00:00:00
abstract::The phenotypic properties of ICP27 temperature-sensitive and deletion mutants and the results of transient expression assays have demonstrated that ICP27 has a modulatory effect on viral gene expression induced by ICPs 0 and 4. In order to identify the regions of the ICP27 molecule that are responsible for its enhanci...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.7.3471-3485.1990
更新日期:1990-07-01 00:00:00
abstract::The bovine herpesvirus 1 (BHV-1) UL49 gene encodes a viral tegument protein termed VP22. UL49 homologs are conserved among alphaherpesviruses. Interestingly, the BHV-1 VP22 deletion mutant virus is asymptomatic and avirulent in infected cattle but produces only a slight reduction in titer in vitro. Attenuation of the ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.75.17.8251-8258.2001
更新日期:2001-09-01 00:00:00
abstract::We report several biological activities of a synthetic peptide whose sequence contains the highly conserved region of feline leukemia virus transmembrane protein (TM) synthetically linked to another short TM-derived sequence particularly rich in polar positive residues. This 29-amino-acid peptide blocked [3H]thymidine...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.64.4.1429-1436.1990
更新日期:1990-04-01 00:00:00
abstract::Hepatitis delta virus (HDV), a single-stranded RNA virus, bears a single coding region whose product, the hepatitis delta antigen (HDAg), is expressed in two isoforms, small (S-HDAg) and large (L-HDAg). S-HDAg is required for replication of HDV, while L-HDAg inhibits viral replication and is required for the envelopme...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.74.11.5329-5336.2000
更新日期:2000-06-01 00:00:00
abstract::Bovine leukemia virus (BLV) and human T-cell lymphotropic virus type 1 (HTLV-1) belong to the genus of deltaretroviruses. Their entry into the host cell is supposed to be mediated by interactions of the extracellular (SU) envelope glycoproteins with cellular receptors. To gain insight into the mechanisms governing thi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.76.16.7956-7967.2002
更新日期:2002-08-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) R5 isolates that predominantly use CCR5 as a coreceptor are frequently described as macrophage tropic. Here, we compare macrophage tropism conferred by HIV-1 R5 envelopes that were derived directly by PCR from patient tissue. This approach avoids potentially selective cultur...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02328-05
更新日期:2006-07-01 00:00:00
abstract::Newborn mice suckled on dams immunized either orally or parenterally with primate rotavirus SA-11 were protected against diarrhea induced by SA-11 virus challenge. Experimental oral administration of milk from orally immunized dams protected suckling mice against challenge; protective activity was detected both in the...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.54.1.58-64.1985
更新日期:1985-04-01 00:00:00
abstract::The nature and theory of flow field-flow fractionation is described, and its potential applicability to virus-like particles is discussed. Different virus types are shown to be retained at different levels. Retention can be controlled by variation of the experimental parameters, in good agreement with theory. However,...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.21.1.131-138.1977
更新日期:1977-01-01 00:00:00
abstract::A polypeptide (p40) of approximately 40,000 molecular weight was isolated from herpes simplex virus type 1 and 2 nucleocapsids by gel filtration and ion exchange chromatography. This protein appears to be the same as protein 22a described previously (Gibson and Roizman, J. Virol. 10:1044--1052, 1972). Competition immu...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.29.1.34-42.1979
更新日期:1979-01-01 00:00:00
abstract::A recent publication indicated that overexpression of Axl, a cellular receptor that negatively regulates Toll-like receptor signaling, enhanced the entry of viruses pseudotyped with the glycoprotein of lymphocytic choriomeningitis virus (LCMV) in vitro. In testing the biological relevance of these observations, we fou...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03268-12
更新日期:2013-04-01 00:00:00
abstract::The majority of HIV-1 infections around the world result from non-B clade HIV-1 strains. The CRF01_AE (AE) strain is seen principally in Southeast Asia. AE protease differs by approximately 10% in amino acid sequence from clade B protease and carries several naturally occurring polymorphisms that are associated with d...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00505-10
更新日期:2010-10-01 00:00:00
abstract::We have previously demonstrated that the human papillomavirus (HPV) genome replicates effectively in U2OS cells after transfection using electroporation. The transient extrachromosomal replication, stable maintenance, and late amplification of the viral genome could be studied for high- and low-risk mucosal and cutane...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01943-12
更新日期:2013-01-01 00:00:00
abstract::To study the tissue specificity of mouse mammary tumor virus (MMTV) gene expression, we developed two series of transgenic mice, containing the MMTV proviral DNA of mammary (GR) and kidney (C3H-K) origin. The expression pattern in the MMTV(GR) transgenic mice is very similar to that observed in infected animals, e.g.,...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.66.7.4580-4586.1992
更新日期:1992-07-01 00:00:00
abstract::Brome mosaic virus (BMV), a member of the alphavirus-like super-family of positive-strand RNA viruses, encodes two proteins required for viral RNA replication: 1a and 2a. 1a contains m7G methyltransferase- and helicase-like domains, while 2a contains a polymerase (pol)-like core flanked by N- and C-terminal extensions...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.7.4729-4736.1996
更新日期:1996-07-01 00:00:00