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

Abstract

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.

Vaccination of mice with recombinant baculovirus expressing spike or nucleocapsid protein of SARS-like coronavirus generates humoral and cellular immune responses

“…Th1 (IFN-␥) and Th2 (IL-4) cytokines were examined by ELISPOT and a strong bias towards Th1 production was detected. Our results are consistent with those observed in other SARS DNA vaccine studies (Huang et al, 2006;Kong et al, 2005;Woo et al, 2005;Yang et al, 2004;Zakhartchouk et al, 2005). The balance between Th1 and Th2 responses to an infectious agent can influence both pathogen growth and immunopathology.…”

Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies

“…The emergence of the SARS-CoV has also led to the development of new vaccine strategies, including expression of SARS-CoV spike protein in other viruses [77,78,79,80,81,82,83,84,85], inactivated SARS-CoV particles [82,86,87,88,89,90,91] or DNA vaccines [92,93,94,95]. However, an early concern for application of a SARS-CoV vaccine was the experience with animal coronavirus vaccines, which induced enhanced disease and immunopathology in animals when challenged with infectious virus [96].…”

A recombinant baculovirus-expressed S glycoprotein vaccine elicits high titers of SARS-associated coronavirus (SARS-CoV) neutralizing antibodies in mice

“…There are also several subunit vaccines in pre-clinical development, targeting SARS-CoV structural proteins, including the spike (S) and nucleocapsid (N) proteins. Other vaccine candidates include vector-based DNA vaccines [7][8][9][10][11], a combination of whole killed virus and DNA vaccines [12], inactivated whole virus vaccines [13,14], a combination of DNA and S-peptide vaccines [15], and other recombinant proteins and their fragments.…”