title: Formalin-treated UV-inactivated SARS coronavirus vaccine retains its immunogenicity and promotes Th2-type immune responses.
abstract: The demand for rapid and simple development of a vaccine against a newly emerging infectious disease is increasing worldwide. We previously revealed that UV-inactivated severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) virions (UV-V) elicited high levels of humoral immunity and a weak Th0 response in mice immunized subcutaneously. To ensure the safety of such a whole inactivated SARS-CoV vaccine, we additionally treated the UV-V vaccine with formalin, resulting in the UV-F-V vaccine. Analysis of the immunogenicity of the UV-F-V+alum vaccine in mice revealed that it generated comparable neutralizing serum anti-SARS-CoV IgG antibody levels as the UV-V+alum vaccine. Moreover, both vaccines induced similar frequencies of anti-SARS-CoV IgG antibody-producing cells in bone marrow. Interestingly, the UV-F-V vaccine induced fewer IgG(2a) subtype antibodies and higher interleukin-4 production in vaccinated mice than did UV-V. Thus, UV-F-V imposes a Th2-type bias on the immune response, unlike UV-V. We propose here that doubly-inactivated SARS-CoV virions by UV and formalin constitute a safe vaccine that may effectively induce neutralizing antibodies in humans.
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan. yyokota@nih.go.jp
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tsunetsugu-Yokota
authors.forename: Manabu
authors.initials: M
authors.lastname: Ato
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kaji
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kuraoka
authors.forename: Ki-ichi
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Yu-ya
authors.initials: YY
authors.lastname: Mitsuki
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Masamichi
authors.initials: M
authors.lastname: Oshima
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohnishi
authors.forename: Toshitada
authors.initials: T
authors.lastname: Takemori
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control*; D018418:Th2 Cells / Q000276:immunology*; D014466:Ultraviolet Rays; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D005557:Formaldehyde