T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV

Antiviral Research
Volume 137, January 2017, Pages 82-92

William J .Liu, Min Zhao,Kefang Liu, Kun Xud, Gary Wong, Wenjie Tan, George F. Gao

Abstract

Over 12 years have elapsed since severe acute respiratory syndrome (SARS) triggered the first global alert for coronavirus infections. Virus transmission in humans was quickly halted by public health measures and human infections of SARS coronavirus (SARS-CoV) have not been observed since. However, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of Middle East respiratory syndrome (MERS) in humans. The work on SARS-CoV widens our knowledge on the epidemiology, pathophysiology and immunology of coronaviruses and may shed light on MERS coronavirus (MERS-CoV). It has been confirmed that T-cell immunity plays an important role in recovery from SARS-CoV infection. Herein, we summarize T-cell immunological studies of SARS-CoV and discuss the potential cross-reactivity of the SARS-CoV-specific immunity against MERS-CoV, which may provide useful recommendations for the development of broad-spectrum vaccines against coronavirus infections.

Keywords

SARS-CoV, MERS-CoV, Vaccine, T-cell, Epitope, Cross-reactivity

Antibody-mediated synergy and interference in the neutralization of SARS-CoV at an epitope cluster on the spike protein

Biochemical and Biophysical Research Communications
Volume 390, Issue 3, 18 December 2009, Pages 1056-1060

Lilin Zhong, Lia Haynes, Evi Budo Struble, Azaibi Tamin, Maria Luisa Virata-Theimer, Pei Zhang.

Abstract

Incomplete neutralization of virus, especially when it occurs in the presence of excess neutralizing antibody, represents a biological phenomenon that impacts greatly on antibody-mediated immune prophylaxis of viral infection and on successful vaccine design. To understand the mechanism by which a virus escapes from antibody-mediated neutralization, we have investigated the interactions of non-neutralizing and neutralizing antibodies at an epitope cluster on the spike protein of severe acute respiratory syndrome coronavirus (SARS-CoV). The epitope cluster was mapped at the C-terminus of the spike protein; it consists of structurally intertwined epitopes recognized by two neutralizing monoclonal antibodies (mAbs), 341C and 540C, and a non-neutralizing mAb, 240C. While mAb 341C binds to a mostly linear epitope composed of residues 507PAT509 and V349, mAb 240C binds to an epitope that partially overlaps the former by at least two residues (P507 and A508). The epitope corresponding to mAb 540C is a conformational one, involving residues L504 and N505. In neutralization assays, non-neutralizing 240C disrupted virus neutralization by mAb 341C and/or mAb 540C, whereas a combination of mAbs 341C and 540C blocked virus infectivity synergistically. These findings indicate that the epitope cluster on the spike protein may serve as an evolutionarily conserved platform at which a dynamic interplay between neutralizing and non-neutralizing antibodies occurs, thereby determining the outcome of SARS-CoV infection.

Keywords

SARS-CoV, Monoclonal antibody, Neutralization, Epitope

A chimeric multi-epitope DNA vaccine elicited specific antibody response against severe acute respiratory syndrome-associated coronavirus which attenuated the virulence of SARS-CoV in vitro

Immunology Letters
Volume 119, Issues 1–2, 15 August 2008, Pages 71-77

Xiaohua Wang, Wei Xu, Deyan Tong, Jing Ni, Haifeng Gao, Ying Wang, Yiwei Chu, Pingping Li, Xiaoming Yang, Sidong Xiong.

Abstract

Epitope-based vaccines designed to induce antibody responses specific for severe acute respiratory syndrome-associated coronavirus (SARS-CoV) are being developed as a means for increasing vaccine potency. In this study, we identified four B cell epitopes from the spike (S) and membrane (M) protein through bioinformatics analysis and constructed a multi-epitope DNA vaccine. Intramuscular immunization of mice with this vaccine was sufficient to induce specific prime as well as a long-term memory humoral immune response to at least two candidate epitopes, S437–459 and M1–20. A DNA prime–protein boost strategy greatly enhanced the antibody generation and the immune sera not only reacted with the lysates of SARS-CoV-infected Vero cells but also neutralized the cytopathic effect of SARS by 75% at 1:160 dilution. The novel immunogenic S protein peptide revealed in this study provides new target for SARS vaccine design; and our work indicated multi-epitope DNA vaccine as an effective means for eliciting polyvalent humoral immune response against SARS-CoV.

Keywords

SARS-CoV, Epitope, DNA vaccine, Antibody, Prime–boost

Priming with SARS CoV S DNA and boosting with SARS CoV S epitopes specific for CD4+ and CD8+ T cells promote cellular immune responses

Vaccine
Volume 25, Issues 39–40, 28 September 2007, Pages 6981-6991

Jun Huang, Yingnan Cao, Jiali Du, Xianzhang Bu, Rui Ma, Changyou Wu.

Abstract

Cellular immune response plays an important role in antiviral immunity. In our previous study, immunization of mice with severe acute respiratory syndrome coronavirus (SARS CoV) spike (S) DNA vaccine could induce both humoral and cellular immunity in response to a pool of entire overlapping S peptides. Identification of functional dominant epitopes in SARS CoV S protein for T cells is crucial for further understanding of cellular immune responses elicited by SARS CoV S DNA vaccine. In present study, mice were immunized with SARS CoV S DNA vaccine. Subsequently, a pool of 17–19 mers overlapped SARS CoV S peptides, which served as immunogens, were scanned to identify the specific epitopes for T cells. Two H-2d restricted CD4+ T epitopes, N60 (S435–444) and P152 (S1111–1127), and two H-2d restricted CD8+ T cell epitopes, N50 (S365–374) and P141 (S1031–1047) were identified by three different methods, enzyme-linked immunosorbent assay (ELISA), enzyme linked immunospot assay (ELISPOT) and fluorescence activated cell sorter (FACS). The dominant CD4+ T cell epitope (N60) and CD8+ T cell epitope (N50) located in the receptor-binding domain (RBD) of SARS CoV S protein, which mediated virus combining and fusing to susceptible cells. Importantly, our novel finding is that mice primed with SARS S DNA vaccine and boosted with T cell epitopes (N50 and N60) could promote antigen specific CD4+ and CD8+ T cell immune responses. Our study provides valuable information for the design of vaccine for SARS study.

Keywords

SARS CoV, T cells, Epitope, Vaccines

Monoclonal antibodies to SARS-associated coronavirus (SARS-CoV): Identification of neutralizing and antibodies reactive to S, N, M and E viral proteins

Journal of Virological Methods
Volume 128, Issues 1–2, September 2005, Pages 21-28

Ralph A. Tripp, Lia M. Haynes, Deborah Moore, Barbara Anderson, Azaibi Tamin, Brian H. Harcourt, Les P. Jones, Mamadi Yilla, Gregory J. Babcock, Thomas Greenough, Donna M. Ambrosino, Rene Alvareza, Justin Callaway, Sheana Cavitt, Kurt Kamrud, Harold Alterson, Jonathan Smith, Jennifer L. Harcourt…Larry J. Anderson.

Abstract

Monoclonal antibodies (Mabs) against the Urbani strain of the SARS-associated coronavirus (SARS-CoV) were developed and characterized for reactivity to SARS-CoV and SARS-CoV S, N, M, and E proteins using enzyme-linked immunoabsorbent (ELISA), radioimmunoprecipitation, immunofluorescence, Western Blot and microneutralization assays. Twenty-six mAbs were reactive to SARS-CoV by ELISA, and nine were chosen for detailed characterization. Five mAbs reacted against the S protein, two against the M protein, and one each against the N and E proteins. Two of five S protein mAbs neutralized SARS-CoV infection of Vero E6 cells and reacted to an epitope within amino acids 490–510 in the S protein. While two of the three non-neutralizing antibodies recognized at second epitope within amino acids 270–350. The mAbs characterized should prove useful for developing SARS-CoV diagnostic assays and for studying the biology of infection and pathogenesis of disease.

Keywords

SARS-coronavirus, Monoclonal antibody, Immunoassay, Epitope, Neutralizing