Augmentation of immune responses to SARS coronavirus by a combination of DNA and whole killed virus vaccines

We studied the immunogenicity of a DNA SARS-vaccine, a whole killed virus, or a whole killed and DNA vaccine combination. The DNA vaccine contained a plasmid encoding the SARS coronavirus (SARS-CoV) S protein under the control of the human CMV promoter and intron A. The whole killed virus vaccine was comprised of SARS-CoV, propagated in Vero-E6 cells, with subsequent beta-propilactone inactivation and formulated with aluminum hydroxide adjuvant. Mice immunized twice with the DNA vaccine and once with the whole killed virus elicited higher antibody responses than mice immunized three times with the DNA vaccine or once with the whole killed virus vaccine. Mice immunized twice with the whole killed virus vaccine elicited higher antibody responses than mice immunized three times with the DNA vaccine or once with the whole killed virus vaccine. However, a combination of the vaccines induced T-helper type 1 (Th1) immune responses while the whole killed virus vaccine induced T helper type 2 (Th2) immune response. These results demonstrate that combination of the DNA vaccine and the whole killed virus vaccine can be used to enhance the magnitude and change the bias of the immune responses to SARS-CoV.