SARS-CoV-2 Omicron BA.4/BA.5 Mutations in Spike Leading to T Cell Escape in Recently Vaccinated Individuals.

SARS-CoV-2 Omicron (B.1.1.529) lineages rapidly became dominant in various countries reflecting its enhanced transmissibility and ability to escape neutralizing antibodies. Although T cells induced by ancestral SARS-CoV-2-based vaccines also recognize Omicron variants, we showed in our previous study that there was a marked loss of T cell cross-reactivity to spike epitopes harboring Omicron BA.1 mutations. The emerging BA.4/BA.5 subvariants carry other spike mutations than the BA.1 variant. The present study aims to investigate the impact of BA.4/BA.5 spike mutations on T cell cross-reactivity at the epitope level. Here, we focused on universal T-helper epitopes predicted to be presented by multiple common HLA class II molecules for broad population coverage. Fifteen universal T-helper epitopes of ancestral spike, which contain mutations in the Omicron BA.4/BA.5 variants, were identified utilizing a bioinformatic tool. T cells isolated from 10 subjects, who were recently vaccinated with mRNA-based BNT162b2, were tested for functional cross-reactivity between epitopes of ancestral SARS-CoV-2 spike and the Omicron BA.4/BA.5 spike counterparts. Reduced T cell cross-reactivity in one or more vaccinees was observed against 87% of the tested 15 non-conserved CD4+ T cell epitopes. These results should be considered for vaccine boosting strategies to protect against Omicron BA.4/BA.5 and future SARS-CoV-2 variants.

Analytical Sensitivity of Eight Different SARS-CoV-2 Antigen-Detecting Rapid Tests for Omicron-BA.1 Variant.

The emergence of each novel SARS-CoV-2 variant of concern (VOC) requires investigation of its potential impact on the performance of diagnostic tests in use, including antigen-detecting rapid diagnostic tests (Ag-RDTs). Although anecdotal reports have been circulating that the newly emerged Omicron-BA.1 variant is in principle detectable by Ag-RDTs, few data on sensitivity are available. We have performed (i) analytical sensitivity testing with cultured virus in eight Ag-RDTs and (ii) retrospective testing in duplicates with clinical samples from vaccinated individuals with Omicron-BA.1 (n = 59) or Delta (n = 54) breakthrough infection on seven Ag-RDTs. Overall, in our analytical study we have found heterogenicity between Ag-RDTs for detecting Omicron-BA.1. When using cultured virus, we observed a trend toward lower endpoint sensitivity for Omicron-BA.1 detection than for earlier circulating SARS-CoV-2 and the other VOCs. In our retrospective study, the detection of Delta and Omicron-BA.1 was assessed in a comparable set of stored clinical samples using seven Ag-RDTs. Four hundred ninety-seven of all 826 tests (60.17%) performed on Omicron-BA.1 samples were positive, compared to 489/756 (64.68%) for Delta samples. In the analytical study, the sensitivity for both Omicron-BA.1 and Delta between the Ag-RDTs was variable. All seven Ag-RDTs showed comparable sensitivities to detect Omicron-BA.1 and Delta in the retrospective study. IMPORTANCE Sensitivity for detecting Omicron-BA.1 shows high heterogenicity between Ag-RDTs, necessitating a careful consideration when using these tests to guide infection prevention measures. Analytical and retrospective testing is a proxy and timely solution to generate rapid performance data, but it is not a replacement for clinical evaluations, which are urgently needed. Biological and technical reasons for detection failure by some Ag-RDTs need to be further investigated.

Estimating the incubation period of SARS-CoV-2 Omicron BA.1 variant in comparison with that during the Delta variant dominance in South Korea.

Based on exposure history and symptom onset of 22 Omicron BA.1 cases in South Korea from November to December 2021, we estimated mean incubation period of 3.5 days (95% CI: 2.5, 3.8), and then compared to that of 6.5 days (95% CI: 5.3, 7.7) for 64 cases during Delta variants' dominance in June 2021. For Omicron BA.1 variants, we found that 95% of symptomatic cases developed clinical conditions within 6.0 days (95% CI: 4.3, 6.6) after exposure. Thus, a shorter quarantine period may be considered based on symptoms, or similarly laboratory testing, when Omicron BA.1 variants are circulating.

Omicron BA.1 Mutations in SARS-CoV-2 Spike Lead to Reduced T-Cell Response in Vaccinated and Convalescent Individuals.

Omicron BA.1 variant can readily infect people with vaccine-induced or naturally acquired SARS-CoV-2 immunity facilitated by escape from neutralizing antibodies. In contrast, T-cell reactivity against the Omicron BA.1 variant seems relatively well preserved. Here, we studied the preexisting T cells elicited by either vaccination with the mRNA-based BNT162b2 vaccine or by natural infection with ancestral SARS-CoV-2 for their cross-reactive potential to 20 selected CD4+ T-cell epitopes of spike-protein-harboring Omicron BA.1 mutations. Although the overall memory CD4+ T-cell responses primed by the ancestral spike protein was still preserved generally, we show here that there is also a clear loss of memory CD4+ T-cell cross-reactivity to immunodominant epitopes across the spike protein due to Omicron BA.1 mutations. Complete or partial loss of preexisting T-cell responsiveness was observed against 60% of 20 nonconserved CD4+ T-cell epitopes predicted to be presented by a broad set of common HLA class II alleles. Monitoring such mutations in circulating strains helps predict which virus variants may escape previously induced cellular immunity and could be of concern.