A number of SARS-CoV-2 variants that have evolved to have significant immune escape have emerged worldwide since the COVID-19 outbreak. The efficacy of prime vaccination is waning with the evolution of SARS-CoV-2, and the necessity of booster doses is more and more prominent. Therefore, this study aimed to compare the neutralization activity against the wild type and variants (Beta, Delta, and Omicron) in different prime-boost vaccination regimens. Electronic databases including PubMed, the Cochrane Library, Embase, medRxiv, Wanfang and CNKI were used to retrieve original studies. A total of 16 studies, 9 prime-boost vaccination regimes, and 3134 subjects were included in the meta-analysis and random effect models were used to estimate pooled neutralization titers. The neutralization activity against SARS-CoV-2 showed a significant decline with the evolution of the virus, especially in the populations primed with inactivated vaccines. For homologous immunization, only the populations boosted with mRNA vaccines consistently had a significant rise in neutralization titers (Beta: MD = 0.97; Delta: MD = 1.33; Omicron: MD = 0.74). While the heterologous immunization was more effective, the increment of neutralization titers against wild type, Beta, Delta and Omicron was 1.65 (95% CI: 1.32-1.96), 1.03 (95% CI: 0.53-1.54), 1.46 (95% CI: 1.07-1.85) and 1.15 (95% CI: 0.68-1.61), respectively. With the evolution of SARS-CoV-2, the effectiveness of prime immunization is waning. Although the administration of the booster dose could ameliorate the neutralization titers, homologous immunization regimens were gradually losing their effectiveness. Therefore, a heterologous booster dose is required, especially in populations primed with inactivated vaccines.
Keywords: COVID-19 vaccine; booster; heterologous; homologous; neutralization; variant.