Divergent SARS CoV-2 Omicron-specific T- and B-cell responses in COVID-19 vaccine recipients

Abstract

The severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) Omicron variant (B.1.1.529) is spreading rapidly, even in vaccinated individuals, raising concerns about immune escape. Here, we studied neutralizing antibodies and T-cell responses to SARS-CoV-2 D614G (wildtype, WT), and the B.1.351 (Beta), B.1.617.2 (Delta), and B.1.1.529 (Omicron) variants of concern (VOC) in a cohort of 60 health care workers (HCW) after immunization with ChAdOx-1 S, Ad26.COV2.S, mRNA-1273 or BNT162b2. High binding antibody levels against WT SARS-CoV-2 spike (S) were detected 28 days after vaccination with both mRNA vaccines (mRNA-1273 or BNT162b2), which significantly decreased after 6 months. In contrast, antibody levels were lower after Ad26.COV2.S vaccination but did not wane. Neutralization assays with authentic virus showed consistent cross-neutralization of the Beta and Delta variants in study participants, but Omicron-specific responses were significantly lower or absent (up to a 34-fold decrease compared to D614G). Notably, BNT162b2 booster vaccination after either two mRNA-1273 immunizations or Ad26.COV.2 priming partially restored neutralization of the Omicron variant, but responses were still up to-17-fold decreased compared to D614G. CD4+ T-cell responses were detected up to 6 months after all vaccination regimens; S-specific T-cell responses were highest after mRNA-1273 vaccination. No significant differences were detected between D614G- and variant-specific T-cell responses, including Omicron, indicating minimal escape at the T-cell level. This study shows that vaccinated individuals retain T-cell immunity to the SARS-CoV-2 Omicron variant, potentially balancing the lack of neutralizing antibodies in preventing or limiting severe COVID-19. Booster vaccinations may be needed to further restore Omicron cross-neutralization by antibodies.

T cell response following anti COVID-19 BNT162b2 vaccination is maintained against the SARS-CoV-2 Omicron B.1.1.529 variant of concern

“…Following antigenic stimulation with the spike-derived peptides, a predominant IFNg response was observed in all the examined individuals, ranging from 50 to 400 secreting cells per 10 6 PBMC, and a lower IL-10 response, ranging from 15 to 82 cells per 10 6 PBMC (figure 1 and 1S). The experimental setup included a 48 hours antigen stimulation step, to allow manifestation of reactivity of IL-4-expressing T cell clones potentially present in the samples, however, almost undetectable levels of IL-4 reactivity was determined, in accordance with previous data pertaining to the responses elicited by the BNT162b2 and m1273 vaccines [2,4,[8][9][10][11][12][13].Comparison of the average response to the wild type and Omicron spike (Figure 2), indicated only a slight, non-significant decrease, from 201 IFNg-secreting cells following activation with the wild type spike, to 188 cells responding to the Omicron spike. The IFNg response was higher than that of IL-10, the average ratio of IFNg/IL-10 response being 4.9, indicating a dominant Th1 response with no significant Th2 response.…”

T cell responses to SARS-CoV-2 spike cross-recognize Omicron

“…Finally, confirmation of our results from cohorts in other geographical areas and exposure to other vaccines would offer further reassurance of the maintenance of T cell responses against Omicron. Indeed, emerging data suggest this to be the case 25,[41][42][43][44][45] .…”

Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron

“…It is conceivable that these binding antibodies, which often have non-neutralizing phenotypes in cell culture, contribute to protection from disease as has been seen for other viral infections [9][10][11] . In concert with T cell based immunity 23 , these non-neutralizing but binding antibodies -which frequently target S2 but also the RBD and NTD 14 -could be responsible for the protection from severe disease that has been observed against Omicron in individuals with pre-existing immunity. In addition, the presence of strong binding antibodies suggests that, while some antibodies may have lost affinity for the drifted epitopes, B cells may be recalled when encountering Omicron spike through infection or vaccination.…”