Impact of BNT162b first vaccination on the immune transcriptome of elderly patients infected with the B.1.351 SARS-CoV-2 variant

Abstract

Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. The B.1.351 variant carrying the escape mutation E484K in the receptor binding domain (RBD) is of particular concern, with widespread escape from monoclonal antibody neutralization and a limited protection of patients having received the first dose of the BNT162b vaccine. It is known that completion of two serial immunizations is required for adequate protection; however, characterization of immune responses in individuals who have received only one dose has not been completely defined. There is also a paucity of information on the impact of vaccination on the immune transcriptome upon infection with SARS-CoV-2 variants. Here, we investigate the immune transcriptome of six elderly individuals (average age 82 yr.) from an old people s home, who contracted B.1.351, with four having received the first dose of BNT162b about two weeks prior to the onset of COVID-19 symptoms. The patients were hospitalized and received dexamethasone treatment. Immune transcriptomes were established from PBMCs approximately 10 days and 35 days after the onset of COVID-19 symptomology. RNA-seq revealed a more intensive immune response in vaccinated patients as compared to unvaccinated ones. Specifically, transcription factors linked to the JAK/STAT pathway, interferon stimulated genes (ISGs), and genes associated with innate antiviral immunity and COVID-19-SARS-CoV-2 infection are highly enriched in vaccinated patients. The transcriptomes of the older vaccinated group were more similar to a younger (age 48-62) comparative group than those of the older unvaccinated group. Our study demonstrates an enhanced immune transcriptome response in B.1.351 patients that had received their first vaccination within 11 days prior to developing COVID-19 illness as compared to unvaccinated patients from the same old-people s home. Our study also reveals that induction of immune-regulated genes in vaccinated individuals was insufficient to protect from disease. This highlights the continued risk for severe illness shortly after vaccination, before a protective immune response has been achieved and reinforces the need for vaccinated adults to continue physical distancing and prevention behaviors.