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In a small study involving 54 participants, omicron subvariants BA.2.12.1, BA.4, and BA.5 of SARS-CoV-2 were more likely to escape neutralizing antibodies induced by both vaccination and previous infection than were the prior omicron subvariants BA.1 and BA.2.

The highly mutated SARS-CoV-2 Omicron (B.1.1.529) variant has been shown to evade a substantial fraction of neutralizing antibody responses elicited by current vaccines that encode the WA1/2020 spike protein 1 . Cellular immune responses, particularly CD8 + T cell responses, probably contribute to protection against severe SARS-CoV-2 infection 2 – 6 . Here we show that cellular immunity induced by current vaccines against SARS-CoV-2 is highly conserved to the SARS-CoV-2 Omicron spike protein. Individuals who received the Ad26.COV2.S or BNT162b2 vaccines demonstrated durable spike-specific CD8 + and CD4 + T cell responses, which showed extensive cross-reactivity against both the Delta and the Omicron variants, including in central and effector memory cellular subpopulations. Median Omicron spike-specific CD8 + T cell responses were 82–84% of the WA1/2020 spike-specific CD8 + T cell responses. These data provide immunological context for the observation that current vaccines still show robust protection against severe disease with the SARS-CoV-2 Omicron variant despite the substantially reduced neutralizing antibody responses 7 , 8 . Current vaccines induce broadly cross-reactive cellular immunity against SARS-CoV-2 variants, including Omicron, and provide protection against severe disease despite a substantially reduced neutralizing antibody response.

Although two doses of BNT162b2 vaccine produce immunity that wanes over time, the administration of a booster dose substantially increases the level of neutralizing antibodies against both the BA.1 and BA.2 variants.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant BA.2.86 has over 30 mutations in spike compared with BA.2 and XBB.1.5, which raised the possibility that BA.2.86 might evade neutralizing antibodies (NAbs) induced by vaccination or infection. In this study, we show that NAb titers are substantially lower to BA.2.86 compared with BA.2 but are similar or slightly higher than to other current circulating variants, including XBB.1.5, EG.5.1, and FL.1.5.1. Moreover, NAb titers against all these variants were higher in vaccinated individuals with a history of XBB.1.5 infection compared with vaccinated individuals with no history of XBB.1.5 infection, suggesting the potential utility of the monovalent XBB.1.5 mRNA boosters.

Thrombosis with thrombocytopenia syndrome (TTS) is a rare but potentially severe adverse event following immunization with adenovirus vector-based COVID-19 vaccines such as Ad26.COV2.S (Janssen) and ChAdOx1 (AstraZeneca). However, no case of TTS has been reported in over 1.5 million individuals who received a second immunization with Ad26.COV2.S in the United States. Here we utilize transcriptomic and proteomic profiling to compare individuals who receive two doses of Ad26.COV2.S with those vaccinated with BNT162b2 or mRNA-1273. Initial Ad26.COV2.S vaccination induces transient activation of platelet and coagulation and innate immune pathways that resolve by day 7; by contrast, patients with TTS show robust upregulation of these pathways on days 15–19 following initial Ad26.COV2.S vaccination. Meanwhile, a second immunization or a reduced initial dose of Ad26.COV2.S induces lower activation of these pathways than does the full initial dose. Our data suggest a role of coagulation and proinflammatory pathways in TTS pathogenesis, which may help optimize vaccination regimens to reduce TTS risk. Adenovirus-based vaccination for SARS-CoV-2 has a rare chance to cause thrombosis with thrombocytopenia (TTS). Here the authors compare proteomic and transcriptomic data from vaccinated participants with or without TTS to find distinct activations of coagulation and innate immune pathways in patient with TTS, or following initial or boosting vaccination.

Antibodies and helper T cells play important roles in SARS-CoV-2 infection and vaccination. We sequenced B- and T-cell receptor repertoires (BCR/TCR) from the blood of 251 infectees, vaccinees, and controls to investigate whether features of these repertoires could predict subjects’ SARS-CoV-2 neutralizing antibody titer (NAbs), as measured by enzyme-linked immunosorbent assay (ELISA). We sequenced recombined immunoglobulin heavy-chain (IGH), TCRβ (TRB), and TCRδ (TRD) genes in parallel from all subjects, including select B- and T-cell subsets in most cases, with a focus on their hypervariable CDR3 regions, and correlated this AIRRseq data with demographics and clinical findings from subjects’ electronic health records. We found that age affected NAb levels in vaccinees but not infectees. Intriguingly, we found that vaccination and infection are associated with longer non-productively recombined IGHs, suggesting an effect that precedes clonal selection. We found that TRB repertoires’ binding capacity to known SARS-CoV-2-specific CD4+ TRBs performs as well as the best hand-tuned approximate or “fuzzy” matching at predicting a protective level of NAbs, while also being more robust to repertoire sample size and not requiring hand-tuning. The overall conclusion from this large, unbiased, clinically well annotated dataset is that B- and T-cell adaptive responses to SARS-CoV-2 infection and vaccination are surprising, subtle, and diffuse. We discuss methodological and statistical challenges faced in attempting to define and quantify such strong-but-diffuse repertoire signatures and present tools and strategies for addressing these challenges.

BQ.1.1 and XBB.1 neutralizing antibody titers were lower than those against wild-type strain after boosters in vaccinated and previously infected persons. Both variants expressed the R346T spike mutation.

Neutralization Escape by Omicron BA.4.6Neutralization titers against omicron subvariant BA.4.6 were lower by a factor of 2 to 2.7 than titers against subvariants BA.4 and BA.5 induced by infection or vaccination against SARS-CoV-2.

Response to BA.5 Bivalent BoosterIn a small study, neutralizing antibody titers against the ancestral strain of SARS-CoV-2 were higher than titers against omicron BA.5 after both monovalent and bivalent boosting.

B-cell and T-cell responses were measured to assess the stability and duration of vaccine-induced immunity. Responses to BNT162b2 and mRNA-1273 peaked early and declined over 6 to 8 months. The response to Ad26.CoV2.S reached a lower peak but continued without evidence of notable decline for 8 months. Response levels correlating with protection have not yet been defined.