Immunogenicity of a receptor-binding domain of SARS coronavirus spike protein in mice: implications for a subunit vaccine.
We studied the immunogenicity of an anti-SARS subunit vaccine comprised of the fragment of the SARS coronavirus (SARS-CoV) spike protein amino acids 318-510 (S318-510) containing the receptor-binding domain. The S protein fragment was purified from the culture supernatant of stably transformed HEK293T cells secreting a tagged version of the protein. The vaccine was given subcutaneously to 129S6/SvEv mice in saline, with alum adjuvant or with alum plus CpG oligodeoxynucleotides (ODN). Mice immunized with the adjuvanted antigen elicited strong antibody and cellular immune responses; furthermore, adding the CpG ODN to the alum resulted in increased IgG2a antibody titers and a higher number of INF-gamma-secreting murine splenocytes. Mice vaccinated with S318-510 deglycosylated by PNGase F (dgS318-510) showed a lower neutralizing antibody response but had similar numbers of INF-gamma-producing cells in the spleen. This finding suggests that carbohydrate is important for the immunogenicity of the S318-510 protein fragment and provide useful information for designing an effective and safe SARS subunit vaccine.
Zakhartchouk
Alexander N
AN
Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan, 120 Veterinary Road, Saskatoon, Sask., Canada S7N 5E3. zakhartchouk@sask.usask.ca
Sharon
Chetna
C
Satkunarajah
Malathy
M
Auperin
Thierry
T
Viswanathan
Sathiyanarayanan
S
Mutwiri
George
G
Petric
Martin
M
See
Raymond H
RH
Brunham
Robert C
RC
Finlay
B Brett
BB
Cameron
Cheryl
C
Kelvin
David J
DJ
Cochrane
Alan
A
Rini
James M
JM
Babiuk
Lorne A
LA
D000534:Alum Compounds; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002460:Cell Line; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009838:Oligodeoxyribonucleotides; D011991:Receptors, Virus / Q000378:metabolism*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology / Q000517:prevention & control*; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000534:Alum Compounds; D000914:Antibodies, Viral; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C578557:spike glycoprotein, SARS-CoV; C578553:spike protein, mouse hepatitis virus; C041524:aluminum sulfate; D007371:Interferon-gamma