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Correction: A vesicular stomatitis virus-based prime-boost vaccination strategy induces potent and protective neutralizing antibodies against SARS-CoV-2

Kim, Gyoung Nyoun ; Choi, Jung-ah ; Wu, Kunyu ; [et al.]

Public Library of Science (PLoS) ; 2022

In: PLOS Pathogens Vol. 18, No. 11 ( 2022-11-29), p. e1011000-

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In: PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 11 ( 2022-11-29), p. e1011000-

Type of Medium: Online Resource

ISSN: 1553-7374

URL: Article

DOI: 10.1371/journal.ppat.1011000

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2022

detail.hit.zdb_id: 2205412-1

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A vesicular stomatitis virus-based prime-boost vaccination strategy induces potent and protective neutralizing antibodies against SARS-CoV-2

Kim, Gyoung Nyoun ; Choi, Jung-ah ; Wu, Kunyu ; [et al.]

Public Library of Science (PLoS) ; 2021

In: PLOS Pathogens Vol. 17, No. 12 ( 2021-12-16), p. e1010092-

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In: PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 12 ( 2021-12-16), p. e1010092-

Abstract: The development of safe and effective vaccines to prevent SARS-CoV-2 infections remains an urgent priority worldwide. We have used a recombinant vesicular stomatitis virus (rVSV)-based prime-boost immunization strategy to develop an effective COVID-19 vaccine candidate. We have constructed VSV genomes carrying exogenous genes resulting in the production of avirulent rVSV carrying the full-length spike protein (S F ), the S1 subunit, or the receptor-binding domain (RBD) plus envelope (E) protein of SARS-CoV-2. Adding the honeybee melittin signal peptide (msp) to the N-terminus enhanced the protein expression, and adding the VSV G protein transmembrane domain and the cytoplasmic tail (Gtc) enhanced protein incorporation into pseudotype VSV. All rVSVs expressed three different forms of SARS-CoV-2 spike proteins, but chimeras with VSV-Gtc demonstrated the highest rVSV-associated expression. In immunized mice, rVSV with chimeric S protein-Gtc derivatives induced the highest level of potent neutralizing antibodies and T cell responses, and rVSV harboring the full-length msp-S F -Gtc proved to be the superior immunogen. More importantly, rVSV-msp-S F -Gtc vaccinated animals were completely protected from a subsequent SARS-CoV-2 challenge. Overall, we have developed an efficient strategy to induce a protective response in SARS-CoV-2 challenged immunized mice. Vaccination with our rVSV-based vector may be an effective solution in the global fight against COVID-19.

Type of Medium: Online Resource

ISSN: 1553-7374

URL: Article

DOI: 10.1371/journal.ppat.1010092

DOI: 10.1371/journal.ppat.1010092.g001

DOI: 10.1371/journal.ppat.1010092.g002

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DOI: 10.1371/journal.ppat.1010092.t001

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DOI: 10.1371/journal.ppat.1010092.s018

DOI: 10.1371/journal.ppat.1010092.s019

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2021

detail.hit.zdb_id: 2205412-1

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Targeting the MR1-MAIT cell axis improves vaccine efficacy and affords protection against viral pathogens

Rashu, Rasheduzzaman ; Ninkov, Marina ; Wardell, Christine M. ; [et al.]

Public Library of Science (PLoS) ; 2023

In: PLOS Pathogens Vol. 19, No. 6 ( 2023-6-29), p. e1011485-

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In: PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 6 ( 2023-6-29), p. e1011485-

Abstract: Mucosa-associated invariant T (MAIT) cells are MR1-restricted, innate-like T lymphocytes with tremendous antibacterial and immunomodulatory functions. Additionally, MAIT cells sense and respond to viral infections in an MR1-independent fashion. However, whether they can be directly targeted in immunization strategies against viral pathogens is unclear. We addressed this question in multiple wild-type and genetically altered but clinically relevant mouse strains using several vaccine platforms against influenza viruses, poxviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We demonstrate that 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), a riboflavin-based MR1 ligand of bacterial origin, can synergize with viral vaccines to expand MAIT cells in multiple tissues, reprogram them towards a pro-inflammatory MAIT1 phenotype, license them to bolster virus-specific CD8 + T cell responses, and potentiate heterosubtypic anti-influenza protection. Repeated 5-OP-RU administration did not render MAIT cells anergic, thus allowing for its inclusion in prime-boost immunization protocols. Mechanistically, tissue MAIT cell accumulation was due to their robust proliferation, as opposed to altered migratory behavior, and required viral vaccine replication competency and Toll-like receptor 3 and type I interferon receptor signaling. The observed phenomenon was reproducible in female and male mice, and in both young and old animals. It could also be recapitulated in a human cell culture system in which peripheral blood mononuclear cells were exposed to replicating virions and 5-OP-RU. In conclusion, although viruses and virus-based vaccines are devoid of the riboflavin biosynthesis machinery that supplies MR1 ligands, targeting MR1 enhances the efficacy of vaccine-elicited antiviral immunity. We propose 5-OP-RU as a non-classic but potent and versatile vaccine adjuvant against respiratory viruses.

Type of Medium: Online Resource

ISSN: 1553-7374

URL: Article

DOI: 10.1371/journal.ppat.1011485

DOI: 10.1371/journal.ppat.1011485.g001

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DOI: 10.1371/journal.ppat.1011485.s028

DOI: 10.1371/journal.ppat.1011485.s029

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2023

detail.hit.zdb_id: 2205412-1

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Variable Fitness Impact of HIV-1 Escape Mutations to Cytotoxic T Lymphocyte (CTL) Response

Troyer, Ryan M. ; McNevin, John ; Liu, Yi ; [et al.]

Public Library of Science (PLoS) ; 2009

In: PLoS Pathogens Vol. 5, No. 4 ( 2009-4-3), p. e1000365-

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In: PLoS Pathogens, Public Library of Science (PLoS), Vol. 5, No. 4 ( 2009-4-3), p. e1000365-

Type of Medium: Online Resource

ISSN: 1553-7374

URL: Article

DOI: 10.1371/journal.ppat.1000365

DOI: 10.1371/journal.ppat.1000365.g001

DOI: 10.1371/journal.ppat.1000365.g002

DOI: 10.1371/journal.ppat.1000365.g003

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DOI: 10.1371/journal.ppat.1000365.s001

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DOI: 10.1371/journal.ppat.1000365.s003

DOI: 10.1371/journal.ppat.1000365.s004

DOI: 10.1371/journal.ppat.1000365.s005

DOI: 10.1371/journal.ppat.1000365.s006

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2009

detail.hit.zdb_id: 2205412-1

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Novel Gammaherpesviruses in North American Domestic Cats, Bobcats, and Pumas: Identification, Prevalence, and Risk Factors

Troyer, Ryan M. ; Beatty, Julia A. ; Stutzman-Rodriguez, Kathryn R. ; [et al.]

American Society for Microbiology ; 2014

In: Journal of Virology Vol. 88, No. 8 ( 2014-04-15), p. 3914-3924

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In: Journal of Virology, American Society for Microbiology, Vol. 88, No. 8 ( 2014-04-15), p. 3914-3924

Abstract: Gammaherpesviruses (GHVs) are a diverse and rapidly expanding group of viruses associated with a variety of disease conditions in humans and animals. To identify felid GHVs, we screened domestic cat ( Felis catus ), bobcat ( Lynx rufus ), and puma ( Puma concolor ) blood cell DNA samples from California, Colorado, and Florida using a degenerate pan-GHV PCR. Additional pan-GHV and long-distance PCRs were used to sequence a contiguous 3.4-kb region of each putative virus species, including partial glycoprotein B and DNA polymerase genes. We identified three novel GHVs, each present predominantly in one felid species: Felis catus GHV 1 (FcaGHV1) in domestic cats, Lynx rufus GHV 1 (LruGHV1) in bobcats, and Puma concolor GHV 1 (PcoGHV1) in pumas. To estimate infection prevalence, we developed real-time quantitative PCR assays for each virus and screened additional DNA samples from all three species ( n = 282). FcaGHV1 was detected in 16% of domestic cats across all study sites. LruGHV1 was detected in 47% of bobcats and 13% of pumas across all study sites, suggesting relatively common interspecific transmission. PcoGHV1 was detected in 6% of pumas, all from a specific region of Southern California. The risk of infection for each host varied with geographic location. Age was a positive risk factor for bobcat LruGHV1 infection, and age and being male were risk factors for domestic cat FcaGHV1 infection. Further characterization of these viruses may have significant health implications for domestic cats and may aid studies of free-ranging felid ecology. IMPORTANCE Gammaherpesviruses (GHVs) establish lifelong infection in many animal species and can cause cancer and other diseases in humans and animals. In this study, we identified the DNA sequences of three GHVs present in the blood of domestic cats ( Felis catus ), bobcats ( Lynx rufus ), and pumas ( Puma concolor ; also known as mountain lions, cougars, and panthers). We found that these viruses were closely related to, but distinct from, other known GHVs of animals and represent the first GHVs identified to be native to these feline species. We developed techniques to rapidly and specifically detect the DNA of these viruses in feline blood and found that the domestic cat and bobcat viruses were widespread across the United States. In contrast, puma virus was found only in a specific region of Southern California. Surprisingly, the bobcat virus was also detected in some pumas, suggesting relatively common virus transmission between these species. Adult domestic cats and bobcats were at greater risk for infection than juveniles. Male domestic cats were at greater risk for infection than females. This study identifies three new viruses that are widespread in three feline species, indicates risk factors for infection that may relate to the route of infection, and demonstrates cross-species transmission between bobcats and pumas. These newly identified viruses may have important effects on feline health and ecology.

Type of Medium: Online Resource

ISSN: 0022-538X , 1098-5514

URL: Article

DOI: 10.1128/JVI.03405-13

Language: English

Publisher: American Society for Microbiology

Publication Date: 2014

detail.hit.zdb_id: 1495529-5

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Evolution of Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitopes: Fitness-Balanced Escape

Liu, Yi ; McNevin, John ; Zhao, Hong ; [et al.]

American Society for Microbiology ; 2007

In: Journal of Virology Vol. 81, No. 22 ( 2007-11-15), p. 12179-12188

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In: Journal of Virology, American Society for Microbiology, Vol. 81, No. 22 ( 2007-11-15), p. 12179-12188

Abstract: CD8 + cytotoxic T lymphocytes (CTL) are strong mediators of human immunodeficiency virus type 1 (HIV-1) control, yet HIV-1 frequently mutates to escape CTL recognition. In an analysis of sequences in the Los Alamos HIV-1 database, we show that emerging CTL escape mutations were more often present at lower frequencies than the amino acid(s) that they replaced. Furthermore, epitopes that underwent escape contained amino acid sites of high variability, whereas epitopes persisting at high frequencies lacked highly variable sites. We therefore infer that escape mutations are likely to be associated with weak functional constraints on the viral protein. This was supported by an extensive analysis of one subject for whom all escape mutations within defined CTL epitopes were studied and by an analysis of all reported escape mutations of defined CTL epitopes in the HIV Immunology Database. In one of these defined epitopes, escape mutations involving the substitution of amino acids with lower database frequencies occurred, and the epitope soon reverted back to the sensitive form. We further show that this escape mutation substantially diminished viral fitness in in vitro competition assays. Coincident with the reversion in vivo, we observed the fixation of a mutation 3 amino acids C terminal to the epitope, coincident with the ablation of the corresponding CTL response. The C-terminal mutation did not restore replication fitness reduced by the escape mutation in the epitope and by itself had little effect on replication fitness. Therefore, this C-terminal mutation presumably impaired the processing and presentation of the epitope. Finally, for one persistent epitope, CTL cross-reactivity to a mutant form may have suppressed the mutant to undetected levels, whereas for two other persistent epitopes, each of two mutants showed poor cross-reactivity and appeared in the subject at later time points. Thus, a viral dynamic exists between the advantage of immune escape, peptide cross-reactivity, and the disadvantage of lost replication fitness, with the balance playing an important role in determining whether a CTL epitope will persist or decline during infection.

Type of Medium: Online Resource

ISSN: 0022-538X , 1098-5514

URL: Article

DOI: 10.1128/JVI.01277-07

Language: English

Publisher: American Society for Microbiology

Publication Date: 2007

detail.hit.zdb_id: 1495529-5

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Changes in Human Immunodeficiency Virus Type 1 Fitness and Genetic Diversity during Disease Progression

Troyer, Ryan M. ; Collins, Kalonji R. ; Abraha, Awet ; [et al.]

American Society for Microbiology ; 2005

In: Journal of Virology Vol. 79, No. 14 ( 2005-07), p. 9006-9018

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In: Journal of Virology, American Society for Microbiology, Vol. 79, No. 14 ( 2005-07), p. 9006-9018

Abstract: This study examined the relationship between ex vivo human immunodeficiency virus type 1 (HIV-1) fitness and viral genetic diversity during the course of HIV-1 disease. Primary HIV-1 isolates from 10 patients at different time points were competed against control HIV-1 strains in peripheral blood mononuclear cell (PBMC) cultures to determine relative fitness values. Patient HIV-1 isolates sequentially gained fitness during disease at a significant rate that directly correlated with viral load and HIV-1 env C2V3 diversity. A loss in both fitness and viral diversity was observed upon the initiation of antiretroviral therapy. A possible relationship between genotype and phenotype (virus replication efficiency) is supported by the parallel increases in ex vivo fitness and viral diversity during disease, of which the correlation is largely based on specific V3 sequences. Syncytium-inducing, CXCR4-tropic HIV-1 isolates did have higher relative fitness values than non-syncytium-inducing, CCR5-tropic HIV-1 isolates, as determined by dual virus competitions in PBMC, but increases in fitness during disease were not solely powered by a gradual switch in coreceptor usage. These data provide in vivo evidence that increasing HIV-1 replication efficiency may be related to a concomitant increase in HIV-1 diversity, which in turn may be a determining factor in disease progression.

Type of Medium: Online Resource

ISSN: 0022-538X , 1098-5514

URL: Article

DOI: 10.1128/JVI.79.14.9006-9018.2005

Language: English

Publisher: American Society for Microbiology

Publication Date: 2005

detail.hit.zdb_id: 1495529-5

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Impact of Mutations in Highly Conserved Amino Acids of the HIV-1 Gag-p24 and Env-gp120 Proteins on Viral Replication in Different Genetic Backgrounds

Liu, Yi ; Rao, Ushnal ; McClure, Jan ; [et al.]

Public Library of Science (PLoS) ; 2014

In: PLoS ONE Vol. 9, No. 4 ( 2014-4-8), p. e94240-

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In: PLoS ONE, Public Library of Science (PLoS), Vol. 9, No. 4 ( 2014-4-8), p. e94240-

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0094240

DOI: 10.1371/journal.pone.0094240.g001

DOI: 10.1371/journal.pone.0094240.g002

DOI: 10.1371/journal.pone.0094240.g003

DOI: 10.1371/journal.pone.0094240.g004

DOI: 10.1371/journal.pone.0094240.t001

DOI: 10.1371/journal.pone.0094240.t002

DOI: 10.1371/journal.pone.0094240.t003

DOI: 10.1371/journal.pone.0094240.s001

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2014

detail.hit.zdb_id: 2267670-3

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Rubio, Andrea E. ; Abraha, Awet ; Carpenter, Crystal A. ; [et al.]

Public Library of Science (PLoS) ; 2014

In: PLoS ONE Vol. 9, No. 4 ( 2014-4-11), p. e92084-

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In: PLoS ONE, Public Library of Science (PLoS), Vol. 9, No. 4 ( 2014-4-11), p. e92084-

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0092084

DOI: 10.1371/journal.pone.0092084.g001

DOI: 10.1371/journal.pone.0092084.g002

DOI: 10.1371/journal.pone.0092084.g003

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DOI: 10.1371/journal.pone.0092084.g007

DOI: 10.1371/journal.pone.0092084.t001

DOI: 10.1371/journal.pone.0092084.t002

DOI: 10.1371/journal.pone.0092084.s001

DOI: 10.1371/journal.pone.0092084.s002

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2014

detail.hit.zdb_id: 2267670-3

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Mucosal immunotherapy for protection from pneumonic infection with Francisella tularensis

Troyer, Ryan M. ; Propst, Katie L. ; Fairman, Jeff ; [et al.]

Elsevier BV ; 2009

In: Vaccine Vol. 27, No. 33 ( 2009-7), p. 4424-4433

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In: Vaccine, Elsevier BV, Vol. 27, No. 33 ( 2009-7), p. 4424-4433

Type of Medium: Online Resource

ISSN: 0264-410X

URL: Article

DOI: 10.1016/j.vaccine.2009.05.041

Language: English

Publisher: Elsevier BV

Publication Date: 2009

detail.hit.zdb_id: 1468474-3

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