Immunogenicity of SARS inactivated vaccine in BALB/c mice

Abstract

Severe acute respiratory syndrome (SARS) is a serious infectious threat to public health. To create a novel trial vaccine and evaluate its potency, we attempted to generate a SARS inactivated vaccine using SARS coronavirus (SARS-CoV) strain F69 treated with formaldehyde and mixed with Al(OH)3. Three doses of the vaccine were used to challenge three groups of BALB/c mice. We found that the mice exhibited specific IgM on day 4 and IgG on day 8. The peak titers of IgG were at day 47 in low-dose group (1:19,200) and high-dose group (1:38,400) whereas in middle-dose group (1:19,200), the peak was at day 40. On day 63, the IgG levels reached a plateau. Neutralization assay demonstrated that the antisera could protect Vero-E6 cells from SARS-CoV's infection. Analysis of the antibody specificity revealed that the mouse antisera contained a mixture of antibodies specifically against the structure proteins of SARS-CoV. Furthermore, the mouse antisera conferred higher amount of antibodies against protein N, polypeptide S4 and S2 than those of proteins M and 3CL. These findings suggest that the inactivated SARS-CoV could preserve its antigenicity and the inactivated vaccine can stimulate mice to produce high levels of antibodies with neutralization activity. Results also suggest that polypeptides originating from protein N or S might be a potential target for the generation of a recombinant SARS vaccine.

SARS Vaccine Development

“…However, once the neutralizing epitopes are identified, the inactivated virus vaccine should be replaced by vaccines based on fragments containing neutralizing epitopes since they are safer and more effective. Several reports have showed that SARS-CoV inactivated with formaldehyde, UV light, and β-propiolactone can induce virus-neutralizing antibodies in immunized animals (8)(9)(10)(11), and the first inactivated SARS-CoV vaccine is being tested in the clinical trials in China. However, safety of the inactivated vaccine is a serious concern; production workers are at risk for infection during handling of concentrated live SARS-CoV, incomplete virus inactivation may cause SARS outbreaks among the vaccinated populations, and some viral proteins may induce harmful immune or inflammatory responses, even causing SARS-like diseases (12,13).…”

An sveir model for assessing potential impact of an imperfect anti-SARS vaccine

“…Absent a definitive anti-SARS treatment or vaccine, these efforts were based on the quarantine of suspected cases and isolation of individuals infected with SARS-CoV to stop them from infecting others. Many advances have been made towards the design of a vaccine for SARS, and some vaccines are undergoing clinical trials (see [10,39,44,45,52,53]). This is a welcome development since, historically, vaccines have been and continue to be very useful in preventing illness or death of millions of individuals (see, for instance, [40]).…”

Enhanced Induction of SARS-CoV Nucleocapsid Protein-Specific Immune Response Using DNA Vaccination followed by Adenovirus Boosting in BALB/c Mice

“…Genetic immunization is an encouraging approach to the development of more effective vaccines in the control of some severe viral infections [31] . To prevent and control the re-emerging and transmission of SARS-CoV, except for inactivated vaccine experiments [32][33][34] , several different research reports on DNA vaccines of SARSCoV have been recommended, such as S gene recombinant DNA vaccine [35][36][37][38] , N gene recombinant DNA vaccine [39,40] , and a combination of S, M and N gene recombinant DNA vaccines [41,42] .…”