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

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, S(437-459) and M(1-20). 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.

Protective and Pathologic Roles of the Immune Response to Mouse Hepatitis Virus Type 1: Implications for Severe Acute Respiratory Syndrome

“…CoV infection of mice results in the generation of neutralizing antibodies that are predominantly directed against the receptor-binding domain of the viral spike protein (4, 5, 6, 10, 14,21,43,73,79). Neutralizing antibodies are especially effective at preventing or minimizing infection of cells following reexposure to the pathogen (4,5,6,10,14,21,43,73,79). However, in the context of some CoVs, such as feline infectious peritonitis virus infection of previously immunized cats, and MHV-JHM infection of Rag1-KO mice, the presence of neutralizing antibodies induces opsonization of the virus particles, favoring uptake of these antigen-antibody complexes by Fc-receptor-bearing macrophages (12,32,55).…”

SARS vaccines: where are we?

“…Furthermore, the stability, simplicity, safety and ease of manufacture make DNA vaccines an attractive alternative to the use of live vaccines [90]. Several DNA vaccine candidates have been reported for SARS-CoV proteins, including those for S [12,78,[91][92][93][94], M [95] and N proteins [87,88], all of which can generate antibody and cellular immune responses [94].…”

“…Careful construction of the S plasmid (with splice sites and viral RNA export sequences) has now been shown to markedly increase efficacy of S-DNA vaccine in the mouse model [93], but these vaccines have not been tested in other animal models. A multiple-epitope DNA vaccine strategy elicited induction of antibody responses in mice to two epitopes, S (437-459) and M (1-20), which were able to neutralize SARS-CoV infectivity in vitro [95], but protection was not assessed.…”

A novel DNA vaccine containing multiple TB-specific epitopes casted in a natural structure (ECANS) confers protective immunity against pulmonary mycobacterial challenge

“…Individual experiments were conducted three times, with one representative shown for each group. epitope DNA vaccines have been reported to induce broad CTL responses against HIV, HBV, SARS-CoV and so on [8][9][10]. Introduction of heterologous epitopes into protein carriers by genetic engineering or synthetic coupling method [11] can enhance the Th1 immune responses, induce more potent humoral and cell-mediated immune responses and promote epitope spreading [12].…”