Heterologous prime-boost: breaking the protective immune response bottleneck of COVID-19 vaccine candidates

Abstract

COVID-19 vaccines emerging from different platforms differ in efficacy, duration of protection, and side effects. To maximize the benefits of vaccination, we explored the utility of employing a heterologous prime-boost strategy in which different combinations of the four types of leading COVID-19 vaccine candidates that are undergoing clinical trials in China were tested in a mouse model. Our results showed that sequential immunization with adenovirus vectored vaccine followed by inactivated/recombinant subunit/mRNA vaccine administration specifically increased levels of neutralizing antibodies and promoted the modulation of antibody responses to predominantly neutralizing antibodies. Moreover, a heterologous prime-boost regimen with an 2 adenovirus vector vaccine also improved Th1-biased T cell responses. Our results provide new ideas for the development and application of COVID-19 vaccines to control the SARS-CoV-2 pandemic.

Broad neutralization against SARS-CoV-2 variants induced by a modified B.1.351 protein-based COVID-19 vaccine candidate

“…Because the use of adjuvants is believed to be most important for their role in establishing immunological priming ( 37,38 ), we evaluated and compared the administration of adjuvanted versus non-adjuvanted second doses (boost) and third doses (booster) doses. Animals receiving an adjuvanted boost (antigen plus CpG 1018/alum) induced 2- to 4-fold higher neutralizing antibody titers compared to animals receiving non-adjuvanted boost (antigen-only) (fig.…”

Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine

“…Heterologous prime-boost strategy [22,23], especially a combination of exogenous vaccines (Targeted antigens were delivered into cells like protein based vaccines, inactivated vaccines, and so on) and endogenous vaccines (Targeted antigens were expressed in cells like nucleic acid based vaccines-mRNA vaccine, DNA vaccine, virus vectored vaccine, and so on), has been shown to effectively improve the immunogenicity of HIV-1, influenza, SARS-CoV-2 vaccines [24][25][26][27]. Several regulatory agencies have already begun contemplating putting into practice the concept of heterologous prime-boost strategy or mixed vaccination regimen.…”

Fusion Protein of Rotavirus VP6 and SARS-CoV-2 Receptor Binding Domain Induces T Cell Responses

“…This type of a subunit protein vaccine is extremely safe [ 27 ] and could be used as a standalone vaccine or as a heterologous boost to different vaccination priming strategies. In particular, viral vector-based vaccines, including different adenovirus vectors, may need a heterologous boost due to the vector-induced immune responses over time [ 28 ]. In addition, platform technology is very adaptable, enabling the rapid exchange of antigens of the continuously emerging SARS-CoV-2 variants.…”