High-dimensional analysis of 16 SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity

Abstract

The range of vaccines developed against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) provides a unique opportunity to study immunization across different platforms. In a single-center cohort, we analyzed the humoral and cellular immune compartments following five coronavirus disease 2019 (COVID-19) vaccines spanning three technologies (adenoviral, mRNA and inactivated virus) administered in 16 combinations. For adenoviral and inactivated-virus vaccines, heterologous combinations were generally more immunogenic compared to homologous regimens. The mRNA vaccine as the second dose resulted in the strongest antibody response and induced the highest frequency of spike-binding memory B cells irrespective of the priming vaccine. Priming with the inactivated-virus vaccine increased the SARS-CoV-2-specific T cell response, whereas boosting did not. Distinct immune signatures were elicited by the different vaccine combinations, demonstrating that the immune response is shaped by the type of vaccines applied and the order in which they are delivered. These data provide a framework for improving future vaccine strategies against pathogens and cancer.

Safety and immunogenicity of different booster vaccination schemes for COVID-19 used in El Salvador

“…When applying a dead virus vaccine, such as Sinovac, in the initial scheme, the effectiveness in the induction of antibodies is superior with an mRNA vaccine booster compared to the use of this vaccine in the initial vaccination. Similar results were recently reported in Argentina by the study of Nuñez et al [ 11 ], where the inactivated virus-based Sinopharm vaccine was used and 16 combinations of vaccines were investigated. Humoral and cellular immune responses were superior when this platform was used in the initial scheme and the mRNA vaccine was used as a booster [ 11 ].…”

“…This indicates that the use of a dead virus vaccine in the initial complete scheme and a mRNA vaccine as a booster dose was more effective in inducing an increase in humoral immunity. As it has been demonstrated in other studies, the heterologous schemes, and the use of mRNA vaccines as a booster dose, generates the highest titer of antibodies [ 10 11 18 ]. When applying a dead virus vaccine, such as Sinovac, in the initial scheme, the effectiveness in the induction of antibodies is superior with an mRNA vaccine booster compared to the use of this vaccine in the initial vaccination.…”

“…The mRNA-based Pfizer/BioNtech vaccine was used as a booster in this study. This vaccine has shown to be safe, immunogenic, and highly effective to prevent severe COVID-19 in combination with other platforms [ 10 11 ]. Since different vaccines were employed to prime the Salvadorean population, heterologous or homologous regimes were the options.…”

“…Adenoviral-(AstraZeneca), mRNA-(Pfizer/BioNtech), or complete virus-based vaccines were used for the initial two-dose regimen. The use of heterologous or homologous strategy has proved to protect different populations, but in some countries, it has been demonstrated that the heterologous scheme, using an mRNA-based schemes was superior to the homologous one [ 10 11 ]. This point has been relevant when the priority objective was to accelerate the rate of vaccination.…”

“…Since different platforms for COVID-19 vaccines are used, different heterologous vaccination schemes have been recommended for boosting or completing the initial vaccination protocol since safety parameters are accepted and immunogenicity is superior compared to homologous schemes [ 10 11 ]. In El Salvador, the non-replicating adenovirus vaccine ChAdOx1-S (Oxford AstraZeneca; AstraZeneca, Cambridge, UK), the messenger RNA (mRNA) vaccine BNT162b2 (Pfizer/BioNtech; Pfizer, New York, NY, USA), and the inactivated SARS-CoV-2 vaccine (Sinovac; Sinovac Biotech Ltd., Beijing, China) were used for primary vaccination.…”