Abstract:
UNLABELLED:Although the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) epidemic was controlled by nonvaccine measures, coronaviruses remain a major threat to human health. The design of optimal coronavirus vaccines therefore remains a priority. Such vaccines present major challenges: coronavirus immunity often wanes rapidly, individuals needing to be protected include the elderly, and vaccines may exacerbate rather than prevent coronavirus lung immunopathology. To address these issues, we compared in a murine model a range of recombinant spike protein or inactivated whole-virus vaccine candidates alone or adjuvanted with either alum, CpG, or Advax, a new delta inulin-based polysaccharide adjuvant. While all vaccines protected against lethal infection, addition of adjuvant significantly increased serum neutralizing-antibody titers and reduced lung virus titers on day 3 postchallenge. Whereas unadjuvanted or alum-formulated vaccines were associated with significantly increased lung eosinophilic immunopathology on day 6 postchallenge, this was not seen in mice immunized with vaccines formulated with delta inulin adjuvant. Protection against eosinophilic immunopathology by vaccines containing delta inulin adjuvants correlated better with enhanced T-cell gamma interferon (IFN-γ) recall responses rather than reduced interleukin-4 (IL-4) responses, suggesting that immunopathology predominantly reflects an inadequate vaccine-induced Th1 response. This study highlights the critical importance for development of effective and safe coronavirus vaccines of selection of adjuvants based on the ability to induce durable IFN-γ responses. IMPORTANCE:Coronaviruses such as SARS-CoV and Middle East respiratory syndrome-associated coronavirus (MERS-CoV) cause high case fatality rates and remain major human public health threats, creating a need for effective vaccines. While coronavirus antigens that induce protective neutralizing antibodies have been identified, coronavirus vaccines present a unique problem in that immunized individuals when infected by virus can develop lung eosinophilic pathology, a problem that is further exacerbated by the formulation of SARS-CoV vaccines with alum adjuvants. This study shows that formulation of SARS-CoV spike protein or inactivated whole-virus vaccines with novel delta inulin-based polysaccharide adjuvants enhances neutralizing-antibody titers and protection against clinical disease but at the same time also protects against development of lung eosinophilic immunopathology. It also shows that immunity achieved with delta inulin adjuvants is long-lived, thereby overcoming the natural tendency for rapidly waning coronavirus immunity. Thus, delta inulin adjuvants may offer a unique ability to develop safer and more effective coronavirus vaccines.
journal_name
J Viroljournal_title
Journal of virologyauthors
Honda-Okubo Y,Barnard D,Ong CH,Peng BH,Tseng CT,Petrovsky Ndoi
10.1128/JVI.02980-14subject
Has Abstractpub_date
2015-03-01 00:00:00pages
2995-3007issue
6eissn
0022-538Xissn
1098-5514pii
JVI.02980-14journal_volume
89pub_type
杂志文章abstract::We have demonstrated that intracellular forms of NOTCH1 transactivate two major Epstein-Barr virus (EBV) latent promoters, the LMP1 and Cp1 promoters in an EBV-negative B-cell line, BJAB. Truncated intracellular NOTCH1 associated with the nuclear membrane (DeltaE) transactivates the LMP1 promoter fivefold; however, th...
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pub_type: 杂志文章
doi:10.1128/jvi.74.3.1486-1494.2000
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abstract::DNA sequences encoding the surface envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) were amplified by PCR from uncultured peripheral blood mononuclear cells obtained from patients with serologically defined HIV-1/HIV-2 mixed infections from Bombay, India. HIV-1-specific PCR prod...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.4.2161-2168.1994
更新日期:1994-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.19.3.810-819.1976
更新日期:1976-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.12.9755-9762.1998
更新日期:1998-12-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/JVI.02423-06
更新日期:2007-10-01 00:00:00
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journal_title:Journal of virology
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doi:10.1128/JVI.02420-06
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journal_title:Journal of virology
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doi:10.1128/JVI.00789-09
更新日期:2009-11-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.16.3.736-740.1975
更新日期:1975-09-01 00:00:00
abstract::Inoculation of the leafhopper cell line AC-20 with wound tumor virus resulted in a productive noncytopathic infection with no detectable alteration of cellular protein synthesis. Virus-specific polypeptide synthesis, detectable by 8 h postinoculation, increased in a linear fashion, reaching a peak (approximately 10 to...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.56.2.620-624.1985
更新日期:1985-11-01 00:00:00
abstract::Using a yeast two-hybrid screen of a T-cell cDNA library to identify cellular proteins that bind to the human immunodeficiency virus type 2 (HIV-2) Gag polyprotein, we identified PRP4, a serine-threonine protein kinase. Specific interaction of PRP4 and HIV-2 Gag was confirmed in in vitro and in vivo assays. The intera...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.78.20.11303-11312.2004
更新日期:2004-10-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00558-06
更新日期:2006-09-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.65.9.5013-5028.1991
更新日期:1991-09-01 00:00:00
abstract::Numerous deaths of koi and common carp (Cyprinus carpio) were observed on many farms throughout Israel, resulting in severe financial losses. The lethal viral disease observed is highly contagious and extremely virulent, but morbidity and mortality are restricted to koi and common carp populations. Diseased fish exhib...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.79.4.1983-1991.2005
更新日期:2005-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01237-14
更新日期:2014-08-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.36.3.860-871.1980
更新日期:1980-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01824-07
更新日期:2008-01-23 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.6.6.738-749.1970
更新日期:1970-12-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.03422-13
更新日期:2014-04-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.35.3.812-823.1980
更新日期:1980-09-01 00:00:00
abstract::Human noroviruses are the most common nonbacterial cause of gastroenteritis outbreaks, with new variants and genotypes frequently emerging. The origin of these new viruses is unknown; however, animals have been proposed as a potential source, as human noroviruses have been detected in animal species. Here, we investig...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01492-20
更新日期:2021-01-13 00:00:00
abstract::The polypeptides of three paramyxoviruses (simian virus 5, Newcastle disease virus, and Sendai virus) were separated by polyacrylamide gel electrophoresis. Glycoproteins were identified by the use of radioactive glucosamine as a carbohydrate precursor. The protein patterns reveal similarities among the three viruses. ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.7.1.47-52.1971
更新日期:1971-01-01 00:00:00
abstract::Mature dendritic cells (DCs) are potent antigen-presenting cells essential for initiating successful antiviral immune responses and would therefore serve as an ideal target for viruses seeking to evade or delay the immune response by disrupting their function. We have previously reported that VZV productively infects ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.8.4950-4959.2003
更新日期:2003-04-01 00:00:00
abstract::The human cytomegalovirus (HCMV) UL138 protein downregulates the cell surface expression of the multidrug resistance-associated protein 1 (MRP1) transporter. We examined the genetic requirements within UL138 for MRP1 downregulation. We determined that the acidic cluster dileucine motif is essential for UL138-mediated ...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00430-19
更新日期:2019-05-15 00:00:00
abstract::Simian immunodeficiency virus (SIV) infection of natural hosts is characterized by nonpathogenic chronic viremia, maintenance of gastrointestinal epithelial barrier integrity, and low numbers of target cells. Assessment of cell-associated virus load in T cell subsets in multiple anatomic compartments of chronically SI...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01556-12
更新日期:2012-10-01 00:00:00
abstract::The varicella-zoster virus (VZV) open reading frame 54 (ORF54) gene encodes an 87-kDa monomer that oligomerizes to form the VZV portal protein, pORF54. pORF54 was hypothesized to perform a function similar to that of a previously described herpes simplex virus 1 (HSV-1) homolog, pUL6. pUL6 and the associated viral ter...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00376-14
更新日期:2014-07-01 00:00:00
abstract::A lysate from hypotonically swollen polyoma-infected BALB/3T3 cells incorporated labeled deoxynucleotide triphosphates into both viral and cellular DNAs. The incorporation was stimulated by the presence of ATP, deoxynucleotide triphosphates, thiols, and magnesium ions. Strong inhibition of incorporation was observed w...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.13.1.125-139.1974
更新日期:1974-01-01 00:00:00
abstract:UNLABELLED:The measles virus (MeV) membrane fusion apparatus consists of a fusion protein trimer and an attachment protein tetramer. To trigger membrane fusion, the heads of the MeV attachment protein, hemagglutinin (H), bind cellular receptors while the 96-residue-long H stalk transmits the triggering signal. Structur...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02846-13
更新日期:2014-06-01 00:00:00