Long-term Humoral Immune Memory Response In Survivors Of Severe Acute Respiratory Syndrome (SARS)

Owing much to traditional public health methods of patient isolation and community containment, SARS was contained successfully in June 2003. SARS-CoV resides in hosts such as bats which form its natural reservoir, although the outbreak of SARS seems to be over, SARS is still a safety concern because the re-emergence possibility of the virus from its animal reservoir. It is the persistence and quality of antibody especially its neutralizing activities that determine whether it would protect a person from reinfection, currently many areas about pathology of SARS-CoV infection are unclear:longitudinal profiles of antibody responses against SARS-CoV and its antigenic components in SARS-recovered patients, and how do antibodies operate protection.In the study we have sequentially followed up 19 recovered patients infected with SARS-CoV over a three-year period to characterize the dynamic changes of the whole virus lysates, N protein, S protein and receptor binding domain(RBD) protein specific antibody responses in detail, and to evaluate their neutralizing activities, moreover,4 blood samples were obtained at month 60.The following findings were obtained:First, The average OD reading of N protein specific antibodies fell dramatically between month 3 and month 12, and decreased gradually at low levels which were a little higher than the cut off value from then on. While the average OD reading of S protein specific antibodies decreased gradually throughout the entire phase of the study. Second, sera tested by the whole virus lysates based ELISA kits were at 1/10 dilution, whereas sera tested by S protein based ELISA were at 1/100 dilution. But at month 36, the positive rate of S protein based ELISA was 100%, higher than that of the whole virus lysates based ELISA kits (42%). These results indicated that the sensitivity of S protein based ELISA was higher than that of the whole virus lysates based commercial ELISA kit. Third, neutralizing activities were detectable in 89% recovered patients in the third year, the mean neutralizing activities were 48%. Fourth, IgG levels tested by S protein based ELISA (r=0.717) correlated better than those tested by commercial ELISA kits (r=0.571) with neutralizing activities. Fifth, similar decrease trend was seen between S protein and RBD protein. The sensitivity of RBD protein based ELISA was also higher than that of the whole virus lysates based commercial ELISA kit. IgG levels tested by RBD protein based ELISA (r=0.737) correlated better than those tested by S protein based ELISA (r=0.717) with neutralizing activities. In a word, longitudinal profiles of antibody responses against SARS-CoV and its antigenic components in SARS-recovered patients have been characterized, it is proved that humoral responses have been sustained at least 3 years. The results about RBD protein suggested that RBD protein was a critical neutralization determinant of SARS-CoV during viral infection and immunization, and blockage of the receptor association is the major mechanism of SARS-CoV neutralization. These findings would provide valuable information on natural humoral memory responses in SARS-recovered patients. These data would be helpful for understanding the pathogenesis of SARS-CoV infection, rational design of vaccines and diagnosing kits.