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. 2022 May 18;10(5):798.
doi: 10.3390/vaccines10050798.

Immunogenicity and Safety of Homologous and Heterologous Prime-Boost Immunization with COVID-19 Vaccine: Systematic Review and Meta-Analysis

Haoyue Cheng  1   2 , Zhicheng Peng  1   2 , Shuting Si  1   2 , Xialidan Alifu  1   2 , Haibo Zhou  1   2 , Peihan Chi  1   2 , Yan Zhuang  1   2 , Minjia Mo  1   2 , Yunxian Yu  1   2
Affiliations

Immunogenicity and Safety of Homologous and Heterologous Prime-Boost Immunization with COVID-19 Vaccine: Systematic Review and Meta-Analysis

Haoyue Cheng et al. Vaccines (Basel). .

Abstract

A prime-boost strategy of COVID-19 vaccines brings hope to limit the spread of SARS-CoV-2, while the immunogenicity of the vaccines is waning over time. Whether a booster dose of vaccine is needed has become a widely controversial issue. However, no published meta-analysis has focused on the issue. Therefore, this study assessed the immunogenicity and safety of the different combinations of prime-boost vaccinations. Electronic databases including PubMed, the Cochrane Library, Embase, medRxiv, Wanfang and CNKI were used to retrieve the original studies. A total of 28 studies, 9 combinations of prime-boost vaccinations and 5870 subjects were included in the meta-analysis, and random effect models were used to estimate pooled immunogenicity and safety. The immunity against COVID-19 after the prime vaccination waned over time, especially in the populations primed with inactivated vaccines, in which the seropositive rate of antibodies was only 28% (95% CI: 17-40%). Booster vaccination could significantly increase the antibody responses, and heterologous immunization was more effective than homologous immunization (neutralization titers: 1.65 vs. 1.27; anti-RBD IgG: 1.85 vs. 1.15); in particular, the combination of inactivated-mRNA vaccines had the highest antibody responses (neutralization titers: MRAW = 3.64, 95% CI: 3.54-3.74; anti-RBD IgG: 3.73, 95% CI: 3.59-3.87). Moreover, compared with the initial two doses of vaccines, a booster dose did not induce additional or severe adverse events. The administration of the booster dose effectively recalled specific immune responses to SARS-CoV-2 and increased antibody levels, especially in heterologous immunization. Considering the long-term immunogenicity and vaccine equity, we suggest that now, only individuals primed with inactivated vaccines require a booster dose.

Keywords: COVID-19 vaccine; booster; heterologous; homologous; immunogenicity; safety.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram showing the progress through the stages of meta-analysis.
Figure 2
Figure 2
Forest plot of the pooled log-transformed neutralization antibody titers before booster vaccination.
Figure 3
Figure 3
Forest plot of the pooled log-transformed anti-RBD IgG before booster vaccination.
Figure 4
Figure 4
Forest plot of the pooled seropositive rate of antibodies before booster vaccination.
Figure 5
Figure 5
Forest plot of the pooled log-transformed neutralization antibody titers before and after homologous booster vaccination.
Figure 6
Figure 6
Forest plot of the pooled log-transformed anti-RBD IgG before and after homologous booster vaccination.
Figure 7
Figure 7
Forest plot of the pooled seropositive rate of antibodies before and after homologous booster vaccination.
Figure 8
Figure 8
Forest plot of the pooled log-transformed neutralization antibody titers before and after heterologous booster vaccination.
Figure 9
Figure 9
Forest plot of the pooled log-transformed anti-RBD IgG before and after heterologous booster vaccination.
Figure 10
Figure 10
Forest plot of the pooled seropositive rate of antibodies before and after heterologous booster vaccination.
Figure 11
Figure 11
Forest plot of the overall incidence of total adverse events after booster vaccination.
Figure 12
Figure 12
Forest plot of the overall incidence of local adverse events after booster vaccination.
Figure 13
Figure 13
Forest plot of the overall incidence of systemic adverse events after booster vaccination.
See this image and copyright information in PMC

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