Abstract:
:Vaccination has been used to control the spread of seasonal flu; however, the virus continues to evolve and escape from host immune response through mutation and increasing glycosylation. Efforts have been directed toward development of a universal vaccine with broadly protective activity against multiple influenza strains and subtypes. Here we report the design and evaluation of various chimeric vaccines based on the most common avian influenza H5 and human influenza H1 sequences. Of these constructs, the chimeric HA (cHA) vaccine with consensus H5 as globular head and consensus H1 as stem was shown to elicit broadly protective CD4+ and CD8+ T cell responses. Interestingly, the monoglycosylated cHA (cHAmg) vaccine with GlcNAc on each glycosite induced more stem-specific antibodies, with higher antibody-dependent cellular cytotoxicity (ADCC), and better neutralizing and stronger cross-protection activities against H1, H3, H5, and H7 strains and subtypes. Moreover, the cHAmg vaccine combined with a glycolipid adjuvant designed for class switch further enhanced the vaccine efficacy with more IFN-γ, IL-4, and CD8+ memory T cells produced.
journal_name
Proc Natl Acad Sci U S Aauthors
Liao HY,Wang SC,Ko YA,Lin KI,Ma C,Cheng TR,Wong CHdoi
10.1073/pnas.2004783117subject
Has Abstractpub_date
2020-07-28 00:00:00pages
17757-17763issue
30eissn
0027-8424issn
1091-6490pii
2004783117journal_volume
117pub_type
杂志文章abstract::Endothelial cells (ECs) not only are important for oxygen delivery but also act as a paracrine source for signals that determine the balance between tissue regeneration and fibrosis. Here we show that genetic inactivation of flow-induced transcription factor Krüppel-like factor 2 (KLF2) in ECs results in reduced liver...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1613392114
更新日期:2017-04-11 00:00:00
abstract::Dopamine causes a significant retraction of neurites of bull-head catfish horizontal cells maintained in culture. The effects of dopamine are blocked by haloperidol and SCH 23390, a D1 antagonist, but not by sulpiride, a D2 antagonist. The dopamine-induced morphological changes were mimicked by SKF 38393, a D1 agonist...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.24.9693
更新日期:1990-12-01 00:00:00
abstract::Nature is rife with networks that are functionally optimized to propagate inputs to perform specific tasks. Whether via genetic evolution or dynamic adaptation, many networks create functionality by locally tuning interactions between nodes. Here we explore this behavior in two contexts: strain propagation in mechanic...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1806790116
更新日期:2019-02-12 00:00:00
abstract::The INT6 gene has been implicated in human breast cancer formation, but its function is unknown. We isolated an Int6 homolog from fission yeast, Yin6, by its binding to a conserved protein in the Ras pathway, Moe1. Yin6 and Moe1 converge on the same protein complex to promote microtubule instability/disassembly. Yin6 ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.26.14370
更新日期:2000-12-19 00:00:00
abstract::We utilized the presence of hepatic receptors for galactose-terminal glycoproteins to achieve specific rescue of differentiated hepatocytes from methotrexate toxicity. This was accomplished by administration of a conjugate formed by covalent coupling of the methotrexate antagonist, folinic acid (leucovorin), to galact...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.10.3078
更新日期:1983-05-01 00:00:00
abstract::We have developed a color complementation assay that allows rapid screening of specific genomic DNA sequences. It is based on the simultaneous amplification of two or more DNA segments with fluorescent oligonucleotide primers such that the generation of a color, or combination of colors, can be visualized and used for...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.86.23.9178
更新日期:1989-12-01 00:00:00
abstract::Children who are treated for congenital cataracts later exhibit impairments in configural face analysis. This has been explained in terms of a critical period for the acquisition of normal face processing. Here, we consider a more parsimonious account according to which deficits in configural analysis result from the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1800901115
更新日期:2018-10-30 00:00:00
abstract::Foraminifera are unicellular organisms that inhabit the oceans in various ecosystems. The majority of the foraminifera precipitate calcitic shells and are among the major CaCO(3) producers in the oceans. They comprise an important component of the global carbon cycle and also provide valuable paleoceanographic informa...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0906636106
更新日期:2009-12-22 00:00:00
abstract::In vitro tests for predicting the response of tumors to chemotherapeutic agents might be improved if they were modified to take into account tumor-cell heterogeneity. We have studied the heterogeneity of cellular growth rate and drug response in mouse fibroblast NIH 3T3 cells and in NIH 3T3 cells transformed with the ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.13.4490
更新日期:1987-07-01 00:00:00
abstract::Plasma of normal human individuals was shown to contain an inhibitor of Trypanosoma cruzi neuraminidase (NAase; acylneuraminyl hydrolase, sialidase, EC 3.2.1.18). The inhibitor has been purified to homogeneity by PEG precipitation, CM Affi-Gel Blue Sepharose chromatography, and gel filtration. The purified preparation...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.10.3097
更新日期:1987-05-01 00:00:00
abstract::We describe the partial purification of an endonuclease from calf thymus that nicks phage PM2 DNA irradiated with UV doses producing only a few pyrimidine dimers per molecule. It has much less activity on DNA that has been subjected to enzymatic photoreactivation after UV irradiation. The calf thymus endonuclease is d...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.8.3746
更新日期:1979-08-01 00:00:00
abstract::The structures of the major folding intermediate, the transition state for folding, and the folded state of barnase have been previously characterized. We now add a further step toward a complete picture of the folding of barnase by reporting the backbone 15N, 13C, and 1H NMR assignments for barnase unfolded at pH 1.8...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.20.9412
更新日期:1994-09-27 00:00:00
abstract::Drug resistance testing has been shown to be beneficial for clinical management of HIV type 1 infected patients. Whereas phenotypic assays directly measure drug resistance, the commonly used genotypic assays provide only indirect evidence of drug resistance, the major challenge being the interpretation of the sequence...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.112177799
更新日期:2002-06-11 00:00:00
abstract::The region of human chromosome 22q11 is prone to rearrangements. The resulting chromosomal abnormalities are involved in Velo-cardio-facial and DiGeorge syndromes (VCFS and DGS) (deletions), "cat eye" syndrome (duplications), and certain types of tumors (translocations). As a prelude to the development of mouse models...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.26.14608
更新日期:1997-12-23 00:00:00
abstract::Genetic selections that use proteinaceous transdominant inhibitors encoded by DNA libraries to cause mutant phenocopies may facilitate genetic analysis in traditionally nongenetic organisms. We performed a selection for random short peptides and larger protein fragments (collectively termed "perturbagens") that inhibi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.13.7508
更新日期:1998-06-23 00:00:00
abstract::We have cloned and partially characterized 24 loci from the human genome which are complementary to U1, U2, or U3, the three major species of small nuclear RNA (snRNA) in HeLa cells. When compared to the known U1 (human) and U2 (rat) snRNA sequences, the DNA sequences we report here for the complementary regions from ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.78.2.810
更新日期:1981-02-01 00:00:00
abstract::Hematin administered intravenously in a patient with congenital erythropoietic porphyria evidently entered erythrocyte precursors in the bone marrow, producing the well-known negative feedback repression of porphyrin biosynthesis with marked decline of porphyrin concentrations in urine, circulating plasma, and erythro...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.71.2.278
更新日期:1974-02-01 00:00:00
abstract::We used integrin alphaLbeta2 heterodimers containing I domains locked open (active) or closed (inactive) with disulfide bonds to investigate regulatory interactions among domains in integrins. mAbs to the alphaL I domain and beta2 I-like domain inhibit adhesion of wild-type alphaLbeta2 to intercellular adhesion molecu...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.041618598
更新日期:2001-02-27 00:00:00
abstract::Noonan syndrome (NS) is a relatively common genetic disorder, characterized by typical facies, short stature, developmental delay, and cardiac abnormalities. Known causative genes account for 70-80% of clinically diagnosed NS patients, but the genetic basis for the remaining 20-30% of cases is unknown. We performed ne...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1324128111
更新日期:2014-08-05 00:00:00
abstract::The template for transcription and replication of negative-stranded RNA viruses is a ribonucleoprotein structure, the nucleocapsid. We have developed a system that supports assembly of the negative-stranded RNA genome of a defective interfering (DI) particle of vesicular stomatitis virus (VSV) into a nucleocapsid in v...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.20.7511
更新日期:1988-10-01 00:00:00
abstract::FUS3 is functionally redundant with KSS1, a homologous yeast protein kinase, for a step(s) in signal transduction between the beta subunit of the guanine nucleotide binding protein (G protein), STE4, and the mating type-specific transcriptional activator, STE12. Either FUS3 or KSS1 can execute this function; when neit...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.21.9392
更新日期:1991-11-01 00:00:00
abstract::The aspartate receptor involved in chemotaxis is modified by methyl esterification at four distinct glutamate residues during the adaptive response of this receptor. To explain the high degree of specificity of this modification, it has been proposed that the methyltransferase recognizes the sequence Glu-Glu-Xaa-Xaa-A...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.83.18.6707
更新日期:1986-09-01 00:00:00
abstract::In binocular rivalry, a subject views two incongruent stimuli through each eye but consciously perceives only one stimulus at a time, with a switch in perceptual dominance every few seconds. To investigate the neural correlates of perceptual dominance in humans, seven subjects were recorded with a 148-channel magnetoe...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.6.3198
更新日期:1998-03-17 00:00:00
abstract::TAR DNA-binding protein-43 (TDP-43), a DNA/RNA-binding protein involved in RNA transcription and splicing, has been associated with the pathophysiology of neurodegenerative diseases, including ALS. However, the function of TDP-43 in motor neurons remains undefined. Here we use both gain- and loss-of-function approache...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1003459107
更新日期:2010-09-14 00:00:00
abstract::We have used site-directed mutagenesis of cloned Moloney murine leukemia virus (MuLV) DNA to define a function encoded in the 3' region of the viral pol gene and required for efficient integration of viral DNA. One mutant, MuLV-SF1, contained a single base substitution (C to T at base 4950) that resulted in an arginin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.81.20.6461
更新日期:1984-10-01 00:00:00
abstract::Signaling in the nervous system requires matching of neurotransmitter receptors with cognate neurotransmitters at synapses. The vertebrate neuromuscular junction is the best studied cholinergic synapse, but the mechanisms by which acetylcholine is matched with acetylcholine receptors are not fully understood. Because ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0607450104
更新日期:2007-01-02 00:00:00
abstract::For reasons that are unclear the production of embryonic stem cells from ungulates has proved elusive. Here, we describe induced pluripotent stem cells (iPSC) derived from porcine fetal fibroblasts by lentiviral transduction of 4 human (h) genes, hOCT4, hSOX2, hKLF4, and hc-MYC, the combination commonly used to create...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0905284106
更新日期:2009-07-07 00:00:00
abstract::The mechanisms ensuring balanced growth remain a critical question in developmental biology. In plants, this balance relies on spatiotemporal integration of hormonal signaling pathways, but the understanding of the precise contribution of each hormone is just beginning to take form. Brassinosteroid (BR) hormone is sho...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1417947112
更新日期:2015-01-20 00:00:00
abstract::A yeast genetic system was developed to study how the basic regions of basic-helix-loop-helix (bHLH) proteins distinguish between related consensus bHLH binding sites, with nucleotide sequence CANNTG. The yeast bHLH protein CBF1 binds to the sequence CAC(A/G)TG found in the yeast centromere element CDE1 and in promote...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.2.599
更新日期:1992-01-15 00:00:00
abstract::The Parkinson's disease (PD) substantia nigra is characterized by the presence of Lewy bodies containing fibrillar alpha-synuclein. Early-onset PD has been linked to two point mutations in the gene that encodes alpha-synuclein, suggesting that disease may arise from accelerated fibrillization. However, the identity of...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.97.2.571
更新日期:2000-01-18 00:00:00