A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice

Abstract

The recent emergence of severe acute respiratory syndrome (SARS) was caused by a novel coronavirus, SARS-CoV. It spread rapidly to many countries and developing a SARS vaccine is now urgently required. In order to study the immunogenicity of UV-inactivated purified SARS-CoV virion as a vaccine candidate, we subcutaneously immunized mice with UV-inactivated SARS-CoV with or without an adjuvant. We chose aluminum hydroxide gel (alum) as an adjuvant, because of its long safety history for human use. We observed that the UV-inactivated SARS-CoV virion elicited a high level of humoral immunity, resulting in the generation of long-term antibody secreting and memory B cells. With the addition of alum to the vaccine formula, serum IgG production was augmented and reached a level similar to that found in hyper-immunized mice, though it was still insufficient to elicit serum IgA antibodies. Notably, the SARS-CoV virion itself was able to induce long-term antibody production even without an adjuvant. Anti-SARS-CoV antibodies elicited in mice recognized both the spike and nucleocapsid proteins of the virus and were able to neutralize the virus. Furthermore, the UV-inactivated virion induced regional lymph node T-cell proliferation and significant levels of cytokine production (IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha) upon restimulation with inactivated SARS-CoV virion in vitro. Thus, a whole killed virion could serve as a candidate antigen for a SARS vaccine to elicit both humoral and cellular immunity.

Synthetic Double-Stranded RNA Poly(I:C) Combined with Mucosal Vaccine Protects against Influenza Virus Infection

“…Antigen-specific T-cell responses were measured as previously described (24). Spleens were harvested from mice 1 week after the boost vaccination.…”

Enhanced Induction of SARS-CoV Nucleocapsid Protein-Specific Immune Response Using DNA Vaccination followed by Adenovirus Boosting in BALB/c Mice

“…To prevent and control the re-emerging and transmission of SARS-CoV, except for inactivated vaccine experiments [32][33][34] , several different research reports on DNA vaccines of SARSCoV have been recommended, such as S gene recombinant DNA vaccine [35][36][37][38] , N gene recombinant DNA vaccine [39,40] , and a combination of S, M and N gene recombinant DNA vaccines [41,42] . These genes are delivered and expressed by different plasmids or viral vectors and elicit different levels of humoral and cellular immune responses.…”

Identification and Antigenic Epitope Mapping of Immunodominant Region Amino Residues 510 to 672 on the Spike Protein of the Severe Acute Respiratory Syndrome Coronavirus

“…Presently, some data suggest that protective humoral immunity is achievable Subbarao et al, 2004;ter Meulen et al, 2004;Zheng et al, 2004). Neutralizing antibodies could be induced by inoculation with inactivated vaccines, DNA vaccines, attenuated viruses encoding SARS-CoV spike protein or expressed spike protein (Bisht et al, 2004;Bukreyev et al, 2004;He et al, 2004;Takasuka et al, 2004;Xiong et al, 2004;Yang et al, 2004). For humoral protective immunity, the spike protein of SARS-CoV is the only significant neutralization and protective antigen among the viral structural proteins .…”

“…The spike protein has good antigenicity, and may induce neutralizing antibodies. An inactivated SARS coronavirus vaccine, an attenuated virus vaccine, a recombinant spike protein subunit vaccine, and a spike protein encoding DNA vaccine each have the ability to induce protective neutralization antibodies (Bisht et al, 2004;Bukreyev et al, 2004;He et al, 2004;Takasuka et al, 2004;Xiong et al, 2004;Yang et al, 2004). These features make the SARS-CoV spike protein a suitable candidate for genetic engineering of a subunit vaccine, and suggest it may have diagnostic applications.…”