A subcutaneously injected UV-inactivated SARS coronavirus vaccine elicits systemic humoral immunity in mice.
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.
Department of Immunology, National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan.
Naomi
N
Takasuka
Hideki
H
Fujii
Yoshimasa
Y
Takahashi
Masataka
M
Kasai
Shigeru
S
Morikawa
Shigeyuki
S
Itamura
Koji
K
Ishii
Masahiro
M
Sakaguchi
Kazuo
K
Ohnishi
Masamichi
M
Ohshima
Shu-ichi
S
Hashimoto
Takato
T
Odagiri
Masato
M
Tashiro
Hiroshi
H
Yoshikura
Toshitada
T
Takemori
Yasuko
Y
Tsunetsugu-Yokota
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D015153:Blotting, Western; D007074:Immunoglobulin G / Q000097:blood; D007279:Injections, Subcutaneous; D051379:Mice; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control*; D015164:Vaccines, Inactivated / Q000008:administration & dosage; D014764:Viral Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage*; D014771:Virion / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D007074:Immunoglobulin G; D015164:Vaccines, Inactivated; D014764:Viral Proteins; D014765:Viral Vaccines; C041524:aluminum sulfate