Evaluating the IgG titers targeting the S protein of SARS-CoV-2 by ELISA assays have been used in the development of several anti-SARS-CoV-2 vaccines in China. It is unclear whether the IgG levels against S protein tested by ELISA can monitor immune evasion against different Omicron variants. In the study, 88 recipients immunized with three doses of a COVID-19-inactivated vaccine were enrolled, whose serum samples were collected within 2 months after the third immunization. The IgG antibody levels were detected by using three commercial ELISA kits, which coated the S protein of the prototype, Omicron BA.1 and BA.5 variants respectively. The neutralizing activities of sera against the pseudotyped Omicron variant, prototype was determined. We also analyzed the correlation between the IgG titers with the neutralizing antibodies. The results showed that, after the third dose of the homologous inactivated vaccine, the neutralizing activity against the Omicron variant BA.1(GMT, 60) and BA. 5(GMT, 42) were decreased significantly compared with the prototype (GMT, 331) respectively ( P<0.05). However, the IgG titers against the S of Omicron BA.1(GMT, 2334) and BA.5(GMT, 2447) variants showed no significant difference with the prototype (GMT, 2797). Our results showed different correlation levels between anti-Spike protein of SARS-CoV-2 IgG titers and neutralizing antibodies, against SARS-CoV-2 prototype, Omicron variant BA.1 and BA.5 In summary, our result highlight that the Omicron variant BA.1 and BA.5 escape vaccine-induced immunity by neutralization activity test, and IgG titers against the SARS-CoV-2 Spike protein can not predict the viral immune evasion against different Omicron variants.