International Immunology Advance Access originally published online on August 16, 2004
International Immunology 2004 16(10):1423-1430; doi:10.1093/intimm/dxh143
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© 2004 The Japanese Society for Immunology
A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice
1 Department of Immunology, 2 First, 3 Second and 4 Third Departments of Virology, 5 National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan
Correspondence to: Y. Tsunetsugu-Yokota; E-mail: yyokota{at}nih.go.jp
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-
and TNF-
) 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.
Keywords: alum, cellular immunity, neutralizing antibody, parenteral administration, vaccination
Transmitting editor: K. Sugamura
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