Reactogenicity and immunogenicity of heterologous prime-boost immunization with COVID-19 vaccine

Abstract

Background The objective of the present work was to assess the reactogenicity and immunogenicity of heterologous COVID-19 vaccination regimens in clinical trials and observational studies. Methods PubMed, Cochrane Library, Embase, MedRxiv, BioRxiv databases were searched in September 29, 2021. The PRISMA instruction for systemic review was followed. Two reviewers independently selected the studies, extracted the data and assessed risk of bias. The quality of studies was evaluated using the New Castle-Ottawa and Cochrane risk of instrument. The characteristics and study outcome (e.g., adverse events, immune response, and variant of concern) were extracted. Results Nineteen studies were included in the final data synthesis with 5 clinical trials and 14 observational studies. Heterologous vaccine administration showed a trend toward more frequent systemic reactions. However, the total reactogenicity was tolerable and manageable. Importantly, the heterologous prime-boost vaccination regimens provided higher immunogenic effect either vector/ mRNA-based vaccine or vector/ inactivated vaccine in both humoral and cellular immune response. Notably, the heterologous regimens induced the potential protection against the variant of concern, even to the Delta variant. Conclusions The current findings provided evidence about the higher induction of robust immunogenicity and tolerated reactogenicity of heterologous vaccination regimens (vector-based/mRNA vaccine or vector-based/inactivated vaccine). Also, this study supports the application of heterologous regimens against COVID-19 which may provide more opportunities to speed up the global vaccination campaign and maximize the capacity to control the pandemic.

Dynamics of Neutralizing Antibody and T-Cell Responses to SARS-CoV-2 and Variants of Concern after Primary Immunization with CoronaVac and Booster with BNT162b2 or ChAdOx1 in Health Care Workers

“…Homologous or heterologous COVID-19 prime-boost vaccinations are introduced and reported to improve the humoral and cellular immune responses [ 6 , 7 ]. A homologous third dose of CoronaVac demonstrated increased immune responses against SARS-CoV-2; however, immunogenicity was lower when compared to a heterologous prime-boost with BNT162b2 [ 8 , 9 , 10 , 11 , 12 ].…”

Frequency and Nuisance Level of Adverse Events in Individuals Receiving Homologous and Heterologous COVID-19 Booster Vaccine

“…An increasing number of clinical trials and observational studies have suggested that a heterologous vaccine booster dose (e.g., using the mRNA vaccine after a primary vaccination scheme based on the adenoviral vector vaccine) is generally well-tolerated. Moreover, they evoke robust immunity and, in some cases, may offer additional benefits in terms of greater humoral and T-cell response and, subsequently, higher effectiveness [ 13 , 14 , 15 , 16 , 17 ].…”

“…The data on the reactogenicity of heterologous booster vaccinations compared to homologous schedules are limited. However, some previous studies have shown that receiving the mRNA vaccine after the first dose of adenoviral vector vaccine, or vice versa, may lead to a higher frequency of side effects, mostly mild or moderate, and resolving within 1–3 days [ 16 , 18 , 19 , 20 ]. Some initial observations also indicate that those who receive a heterologous booster dose, regardless of the combination of vaccine types, can expect greater reactogenicity [ 14 , 17 ].…”

COVID-19 Genetic Variants and Their Potential Impact in Vaccine Development

“…In addition, no case of thrombocytopenia appeared among the examined cases. This study revealed that heterogeneous vaccination could have short-term disadvantages, and further studies are needed to determine their safety [ 91 , 92 ].…”

“…The third shot or booster shots may improve the protection against severe disease symptoms [ 97 , 98 ]. Booster shots are usually given after 5–6 months, followed by the second vaccination [ 92 , 99 ]. A booster shot may be needed to maintain protection against virus-related disease.…”