SARS coronavirus spike polypeptide DNA vaccine priming with recombinant spike polypeptide from Escherichia coli as booster induces high titer of neutralizing antibody against SARS coronavirus.
Different forms of SARS coronavirus (SARS-CoV) spike protein-based vaccines for generation of neutralizing antibody response against SARS-CoV were compared using a mouse model. High IgG levels were detected in mice immunized with intraperitoneal (i.p.) recombinant spike polypeptide generated by Escherichia coli (S-peptide), mice primed with intramuscular (i.m.) tPA-optimize800 DNA vaccine (tPA-S-DNA) and boosted with i.p. S-peptide, mice primed with i.m. CTLA4HingeSARS800 DNA vaccine (CTLA4-S-DNA) and boosted with i.p. S-peptide, mice primed with oral live-attenuated Salmonella typhimurium (Salmonella-S-DNA-control) and boosted with i.p. S-peptide, mice primed with oral live-attenuated S. typhimurium that contained tPA-optimize800 DNA vaccine (Salmonella-tPA-S-DNA) and boosted with i.p. S-peptide, and mice primed with oral live-attenuated S. typhimurium that contained CTLA4HingeSARS800 DNA vaccine (Salmonella-tPA-S-DNA) and boosted with i.p. S-peptide. No statistical significant difference was observed among the Th1/Th2 index among these six groups of mice with high IgG levels. Sera of all six mice immunized with i.p. S-peptide, i.m. DNA vaccine control and oral Salmonella-S-DNA-control showed no neutralizing antibody against SARS-CoV. Sera of the mice immunized with i.m. tPA-S-DNA, i.m. CTLA4-S-DNA, oral Salmonella-S-DNA-control boosted with i.p. S-peptide, oral Salmonella-tPA-S-DNA, oral Salmonella-tPA-S-DNA boosted with i.p S-peptide, oral Salmonella-CTLA4-S-DNA and oral Salmonella-CTLA4-S-DNA boosted with i.p. S-peptide showed neutralizing antibody titers of <1:20-1:160. Sera of all the mice immunized with i.m. tPA-S-DNA boosted with i.p. S-peptide and i.m. CTLA4-S-DNA boosted with i.p. S-peptide showed neutralizing antibody titers of >or=1:1280. The present observation may have major practical value, such as immunization of civet cats, since production of recombinant proteins from E. coli is far less expensive than production of recombinant proteins using eukaryotic systems.
Department of Microbiology, The University of Hong Kong, Room 423, University Pathology Building, Queen Mary Hospital, Hong Kong.
Patrick C Y
PC
Woo
Susanna K P
SK
Lau
Hoi-Wah
HW
Tsoi
Zhi-Wei
ZW
Chen
Beatrice H L
BH
Wong
Linqi
L
Zhang
Jim K H
JK
Chan
Lei-Po
LP
Wong
Wei
W
He
Chi
C
Ma
Kwok-Hung
KH
Chan
David D
DD
Ho
Kwok-Yung
KY
Yuen
D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D029968:Escherichia coli Proteins; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008297:Male; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009500:Neutralization Tests; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000517:prevention & control*; D064370:Spike Glycoprotein, Coronavirus; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D001428:Bacterial Vaccines; D029968:Escherichia coli Proteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C578557:spike glycoprotein, SARS-CoV; D015847:Interleukin-4; D007371:Interferon-gamma