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

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.

Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant

“…Regarding the impact of booster vaccine doses on humoral immunity, we showed that heterologous mRNA vaccine boosters elicited higher levels of anti-RBD total antibodies than homologous schedules, as previously reported. 20,21 However, a similar analysis could not be performed for NtAb due to the small sample size.…”

The Effect of a Booster Dose mRNA Vaccine on COVID-19 Infection in Kidney Transplant Recipients after Inactivated or Viral Vector Vaccine Immunization

“…There were two strategies for using the booster dose vaccine: homologous (using the same vaccine platform) and heterologous (using a different vaccine platform) when compared to the previous two doses of the vaccination. Several studies have found that heterologous vaccines outperform homologous vaccines in terms of higher antibody production and T-cell activation in both the general population and KTRs [ 22 , 23 , 38 ]. The rate of seroconversion can be achieved in 60–70% of primary non-responders with a heterologous booster dose, leaving 20–25% of KTRs with no seroconversion after receiving a booster dose [ 15 , 16 , 39 ].…”

“…A booster dose of the vaccination was used to increase antibody levels with the hope that it would reduce incidence and severity of breakthrough infection. Most studies found that a booster dose can significantly increase antibody levels, especially heterologous vaccine platform [ 22 , 23 , 24 , 25 ], but clinical outcomes were not reported. Almost all studies reported results of an mRNA vaccine.…”

Vaccine‐induced binding and neutralizing antibodies against Omicron 6 months after a homologous BNT162b2 booster

“… 7 , 30 , 32 , 33 , 34 This increase was consistent with the rise of binding (median fold increase = 26.8; IQR = 13.6–51.7) 35 , 36 , 37 and neutralizing antibodies (median fold increase = 27.3; IQR = 10.2–52.7). 18 , 19 , 38 , 39 , 40 , 41 However, a waning of protection against symptomatic diseases was rapidly observed 8–14 weeks after the booster (median VE = 37.9%; IQR = 24.6%–45.1%). 7 , 30 , 33 Although protection against severe COVID‐19 remains higher, the Center for Disease Control and Prevention reported that after receiving both 2 and 3 doses, the VE was lower during the Omicron‐predominant than during the Delta‐predominant period at all time points evaluated.…”