Development of vaccines and passive immunotherapy against SARS coronavirus using mouse and SCID-PBL/hu mouse models.
We have investigated novel vaccines strategies against severe acute respiratory syndrome (SARS) CoV infection using cDNA constructs encoding the structural antigens; spike (S), membrane (M), envelope (E), or nucleocapsid (N) protein, derived from SARS CoV (strain HKU39849, TW1, or FFM-1). As SARS-CoV is thought to infect the alveolar epithelial cell of the lung,in the present study, a type II alveolar epithelial cell clone, T7, was used to analyze the mechanism of CTL against SARS CoV membrane antigens. Mice vaccinated with SARS CoV (N) DNA or (M) DNA using pcDNA 3.1 (+) plasmid vector showed T-cell immune responses (CTL induction and proliferation) against type II alveolar epithelial cells (T7) transfected with SARS (N) or (M) DNA, respectively. To determine whether these DNA vaccines could induce T-cell immune responses in humans as well as in mice, SCID-PBL/hu mice were immunized with these DNA vaccines. PBL from healthy human volunteers were administered i.p. into IL-2 receptor gamma-chain-disrupted NOD-SCID mice [IL-2R(-/-) NOD-SCID]. SCID-PBL/hu mice thus constructed can be used to analyze the human immune response in vivo. The SCID-PBL/hu mice were immunized with SARS (N) DNA or (M) DNA and analyzed for a human T-cell immune response. The M DNA vaccine enhanced CTL activity and proliferation in the presence of M peptide in SCID-PBL/hu mice. Furthermore, the SARS N DNA vaccine induced CTL activity (IFN-gamma production by recombinant N protein or N protein-pulsed autologous B blast cells) and proliferation of spleen cells in SCID-PBL/hu mice. These results, demonstrate that SARS M and N DNA vaccines induced human CTL and human T-cell proliferative responses. On the other hand, we have developed SARS DNA vaccines that induce human neutralizing antibodies and human monoclonal antibodies against SARS CoV. Transgenic mice expressing SARS-CoV receptor (angiotensin converting enzyme 2) are also under development. These vaccines are expected to induce immune responses specific for SARS CoV in human and should provide useful tool for development of protective vaccines.
Okada
Masaji
M
Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan.
Takemoto
Yuji
Y
Okuno
Yoshinobu
Y
Hashimoto
Satomi
S
Fukunaga
Yukari
Y
Tanaka
Takao
T
Kita
Yoko
Y
Kuwayama
Sechiko
S
Muraki
Yumiko
Y
Kanamaru
Noriko
N
Takai
Hiroko
H
Okada
Chika
C
Sakaguchi
Yayoi
Y
Furukawa
Izumi
I
Yamada
Kyoko
K
Izumiya
Miwa
M
Yoshida
Shigeto
S
Matsumoto
Makoto
M
Kase
Tetsuo
T
Peiris
J S M
JS
DeMello
Daphne E
DE
Chen
Pei-Jer
PJ
Yamamoto
Naoki
N
Yoshinaka
Yoshiyuki
Y
Nomura
Tatsuji
T
Ishida
Isao
I
Morikawa
Shigeru
S
Tashiro
Masato
M
Sakatani
Mitsunori
M
D000818:Animals; D018920:Coculture Techniques; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics* / Q000378:metabolism*; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control*; D014765:Viral Vaccines
D014765:Viral Vaccines