Identification of synthetic vaccine candidates against SARS CoV infection

Lien, Shu Pei; Shih, Yi Ping; Chen, Hsin–Wei; Tsai, Jy Ping; Leng, Chih Hsiang; Lin, Mei-Ju; Lin, Lijing; Liu, Hsin‐Yu; Chou, Ai Hsiang; Chang, Yu Yin; Chen, Yi Ming A.; Chong, Pele; Liu, Shih‐Jen

doi:10.1016/j.bbrc.2007.04.164

Cited by 16 publications

(13 citation statements)

References 20 publications

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“…Some of these epitopes were described previously, but S521 and S1061 epitopes were newly discovered. Of note, all other previously described H-2 d -restricted T cell epitopes were not recognized by lung-derived T cells in our assays [40,41,42]. These previous reports identified T cell epitopes using adenovirus vectors or DNA constructs expressing single SARS-CoV proteins, or isolated peptides.…”

Section: Am Depletion Before Infection Results In Enhanced T Cell Ressupporting

confidence: 48%

Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice

et al. 2009

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Severe Acute Respiratory Syndrome caused substantial morbidity and mortality during the 2002–2003 epidemic. Many of the features of the human disease are duplicated in BALB/c mice infected with a mouse-adapted version of the virus (MA15), which develop respiratory disease with high morbidity and mortality. Here, we show that severe disease is correlated with slow kinetics of virus clearance and delayed activation and transit of respiratory dendritic cells (rDC) to the draining lymph nodes (DLN) with a consequent deficient virus-specific T cell response. All of these defects are corrected when mice are treated with liposomes containing clodronate, which deplete alveolar macrophages (AM). Inhibitory AMs are believed to prevent the development of immune responses to environmental antigens and allergic responses by interacting with lung dendritic cells and T cells. The inhibitory effects of AM can also be nullified if mice or AMs are pretreated with poly I:C, which directly activate AMs and rDCs through toll-like receptors 3 (TLR3). Further, adoptive transfer of activated but not resting bone marrow–derived dendritic cells (BMDC) protect mice from lethal MA15 infection. These results may be relevant for SARS in humans, which is also characterized by prolonged virus persistence and delayed development of a SARS-CoV-specific immune response in individuals with severe disease.

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Section: Am Depletion Before Infection Results In Enhanced T Cell Ressupporting

confidence: 48%

Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice

et al. 2009

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“…1A). Some of these epitopes were previously identified (8,12,36), while others were not previously described. Further, some epitopes shown to be targets for SARS-CoV-specific T cells in these studies were not recognized by T cells in our assays.…”

Section: Identification and Characterization Of Sars-cov T Cells By Umentioning

confidence: 97%

T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice

Zhao

Perlman

2010

J Virol

358

360

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A dysregulated innate immune response and exuberant cytokine/chemokine expression are believed to be critical factors in the pathogenesis of severe acute respiratory syndrome (SARS), caused by a coronavirus (SARS-CoV). However, we recently showed that inefficient immune activation and a poor virus-specific T cell response underlie severe disease in SARS-CoV-infected mice. Here, we extend these results to show that virus-specific T cells, in the absence of activation of the innate immune response, were sufficient to significantly enhance survival and diminish clinical disease. We demonstrated that T cells are responsible for virus clearance, as intravenous adoptive transfer of SARS-CoV-immune splenocytes or in vitro-generated T cells to SCID or BALB/c mice enhanced survival and reduced virus titers in the lung. Enhancement of the number of virus-specific CD8 T cells by immunization with SARS-CoV peptide-pulsed dendritic cells also resulted in a robust T cell response, earlier virus clearance, and increased survival. These studies are the first to show that T cells play a crucial role in SARS-CoV clearance and that a suboptimal T cell response contributes to the pathological changes observed in SARS. They also provide a new approach to SARS vaccine design.

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“…None of these epitopes appears in our training data sets. Because epitope SP3 is included within the epitope (434-467) (GNYNY-KYRYLKHGKLRPFERDISNVPFSPDGKPC) reported by Lien et al (2007), we omitted the longer epitope.…”

Section: Identifying B-cell Epitopes In the Receptor-binding Domain Omentioning

confidence: 99%

Predicting linear B‐cell epitopes using string kernels

EL-Manzalawy

Dobbs

Honavar

2008

J of Molecular Recognition

646

464

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The identification and characterization of B-cell epitopes play an important role in vaccine design, immunodiagnostic tests, and antibody production. Therefore, computational tools for reliably predicting linear B-cell epitopes are highly desirable. We evaluated Support Vector Machine (SVM) classifiers trained utilizing five different kernel methods using fivefold cross-validation on a homology-reduced data set of 701 linear B-cell epitopes, extracted from Bcipep database, and 701 non-epitopes, randomly extracted from SwissProt sequences. Based on the results of our computational experiments, we propose BCPred, a novel method for predicting linear B-cell epitopes using the subsequence kernel. We show that the predictive performance of BCPred (AUC = 0.758) outperforms 11 SVM-based classifiers developed and evaluated in our experiments as well as our implementation of AAP (AUC = 0.7), a recently proposed method for predicting linear B-cell epitopes using amino acid pair antigenicity. Furthermore, we compared BCPred with AAP and ABCPred, a method that uses recurrent neural networks, using two data sets of unique B-cell epitopes that had been previously used to evaluate ABCPred. Analysis of the data sets used and the results of this comparison show that conclusions about the relative performance of different B-cell epitope prediction methods drawn on the basis of experiments using data sets of unique B-cell epitopes are likely to yield overly optimistic estimates of performance of evaluated methods. This argues for the use of carefully homology-reduced data sets in comparing B-cell epitope prediction methods to avoid misleading conclusions about how different methods compare to each other. Our homologyreduced data set and implementations of BCPred as well as the APP method are publicly available through our web-based server, BCPREDS, at: http://ailab.cs.iastate.edu/bcpreds/.

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Identification of synthetic vaccine candidates against SARS CoV infection

Cited by 16 publications

References 20 publications

Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice

Evasion by Stealth: Inefficient Immune Activation Underlies Poor T Cell Response and Severe Disease in SARS-CoV-Infected Mice

T Cell Responses Are Required for Protection from Clinical Disease and for Virus Clearance in Severe Acute Respiratory Syndrome Coronavirus-Infected Mice

Predicting linear B‐cell epitopes using string kernels

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