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

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-2(d) restricted CD4(+) T epitopes, N60 (S435-444) and P152 (S1111-1127), and two H-2(d) 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.

CD8+ T cell response in HLA-A*0201 transgenic mice is elicited by epitopes from SARS-CoV S protein

“…In view of the advantages of polypeptide vaccine, many teams are trying to identify SARS S epitopes to provide optimum candidates for vaccine development. We have identified two novel epitopes which could induce antigen-specific CD4 + T cell and CD8 + T cell immune responses in BABL/C mice, respectively [18]. However, it is known that the ultimate purpose of scientific research is used by human beings.…”

“…And to respiratory syncytial virus (RSV) infection, CTLs not only contribute to virus elimination, but also induce immunopathology [15,16]. Excited to us, we found that SARS-CoV S specific CTL responses were detected in patients who had recovered from SARS and mouse model [17,18]. Therefore, CTLs may determine the role of immunity in controlling viral pathogenesis.…”

The immune responses of HLA-A*0201 restricted SARS-CoV S peptide-specific CD8+ T cells are augmented in varying degrees by CpG ODN, PolyI:C and R848

“…tive approaches [9][10][11][12]. With regard to SARS-CoV, there have been many T cell epitopes identified by us and other groups [13][14][15][16][17][18]. In our previous study, we have identified five epitopes for CD8 + T cells in HLA-A*0201 transgenic mouse by "DNA prime, peptide boost" strategy [13].…”

A 219-mer CHO-Expressing Receptor-Binding Domain of SARS-CoV S Protein Induces Potent Immune Responses and Protective Immunity

“…Recently developed SARS vaccines are of various categories (18), including inactivated virus vaccines (49,51,59), subunit vaccines (2,26), DNA vaccines (28,42,55), virus-like particles (40,41), viral vector-based vaccines (4,19,34), and different vaccine combinations (16,30,53). A variety of SARS vaccines have been tested in animals, including monkeys, ferrets, mice, and hamsters (1,7,9,20,33,48,49), and some of them have been evaluated in humans (42).…”