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

Abstract

The severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is spreading rapidly, even in vaccinated individuals, raising concerns about immune escape. Here, we studied neutralizing antibodies and T cell responses targeting SARS-CoV-2 D614G [wild type (WT)] and the Beta, Delta, and Omicron variants of concern in a cohort of 60 health care workers 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 substantially decreased after 6 months. In contrast, antibody levels were lower after Ad26.COV2.S vaccination but did not wane. Neutralization assays showed consistent cross-neutralization of the Beta and Delta variants, but neutralization of Omicron was significantly lower or absent. BNT162b2 booster vaccination after either two mRNA-1273 immunizations or Ad26.COV2 priming partially restored neutralization of the Omicron variant, but responses were still up to 17-fold decreased compared with WT. SARS-CoV-2–specific T cells were detected up to 6 months after all vaccination regimens, with more consistent detection of specific CD4 + than CD8 + T cells. No significant differences were detected between WT- and variant-specific CD4 + or CD8 + 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 are needed to further restore Omicron cross-neutralization by antibodies.

Pulmonary lesions following inoculation with the SARS-CoV-2 Omicron BA.1 (B.1.1.529) variant in Syrian golden hamsters

“…A lower inoculation dose of 10 3 PFU in 50 μl, compared to 5.0 x 10 4 PFU in 100 μl used in this study, may explain the differences for one previous study [3]. However, two other studies used even higher doses of 10 5 PFU in 100 μl [12] or 10 5 PFU in 30 μl [4] and only saw limited pathology. In contrast to these studies, where viral stocks were propagated on Vero cells, we used viruses grown on Calu-3 cells, shown to have a cleaved spike protein [23].…”

Humoral and cellular immune memory to four COVID-19 vaccines

“…We did not evaluate recognition of variants, as this was evaluated in independent studies from our laboratories and others (Flemming, 2022; Gao et al, 2022; GeurtsvanKessel et al, 2022; Keeton et al, 2021; Tarke et al ., 2022; Tarke et al, 2021). The current study did not evaluate responses elicited by other vaccine platforms (AstraZeneca, Coronavac, Sinopharm, Sputnik) commonly utilized in other regions because samples from individuals vaccinated with these platforms were not available to us.…”

Omicron BA.1 and BA.2 are antigenically distinct SARS-CoV-2 variants

“…Deep sequencing was performed as described previously 16 . Briefly, RNA was extracted as described above followed by cDNA synthesis and PCR using the QIAseq® SARS-CoV-2 Primer Panel kit (Qiagen) according to the manufacturer's protocol.…”

“…Whereas several earlier VOCs and VOIs exhibit some levels of antibody escape (e.g. Beta, Gamma, Delta, and Mu), they were still neutralized well by convalescent and post-vaccination sera [12][13][14][15][16] . In contrast, Omicron BA.1 almost completely escapes neutralizing antibodies, leading to low levels of remaining protective antibodies in most previously infected or vaccinated individuals, and a high frequency of breakthrough infections.This antibody escape at least partly explains why this variant has become the dominant variant globally over the span of a few weeks [17][18][19][20] .…”

“…Neutralizing activity of human sera against Omicron BA.1 and BA. 2 Multiple studies have shown that Omicron BA.1 efficiently evades antibody responses postinfection and post-vaccination [12][13][14][15][16] . However, few studies have analyzed antibody responses to Omicron BA.2 .…”