Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies

Stark, Caren J; Atreya, CD

Despite these potential pitfalls in the development of a human vaccine, efforts to develop a vaccine to prevent another SARS outbreak are underway. Several laboratories around the globe are working at an unprecedented pace to develop a SARS vaccine utilizing essentially two different types of SARS-CoV-derived immunogens, 1) inactivated whole virus, and 2) SARS-CoV encoded N and S proteins using recombinant DNA methods. The possibility of producing an engineered live, attenuated SARS-CoV has also been considered. Takasuka et al (2004) have reported that subcutaneous administration of UV-inactivated purified SARS-CoV virion elicits a high level of humoral immunity, resulting in long-term antibody secretion and memory B cells [60] . The antibodies elicited in mice recognized both the spike (S) and nucleocapsid (N) proteins of the virus. The inactivated virus also induced regional lymph node T-cell proliferation and significant levels of cytokine production upon restimulation with inactivated virus in vitro [60] . These studies suggest that whole-killed virion may have the potential as a candidate antigen for SARS vaccine to elicit both humoral and cellular immunity. When SARS-CoV inactivated by beta-propiolactone was used as antigen in mice and rabbits, the animals elicited antibodies against the receptor-binding domain (RBD) present in the S1 region of SARS-CoV. These antibodies effectively inhib-ited the S-protein mediated SARS-pseudovirus entry up to 50%, suggesting the potential of the inactivated SARS-CoV as antigen for vaccine development [61] . Depletion of RBD-specific antibodies from patient or rabbit immune sera by immunoadsorption, significantly reduced the virus neutralizing ability of the sera, suggesting that the RBD epitope in the S protein is a critical determinant in developing vaccine strategies [62] .