T‐cell responses to SARS‐CoV‐2 Omicron spike epitopes with mutations after the third booster dose of an inactivated vaccine

Abstract

The rapidly spreading severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Omicron variant contains more than 30 mutations that mediate escape from antibody responses elicited by prior infection or current vaccines. Fortunately, T‐cell responses are highly conserved in most individuals, but the impacts of mutations are not clear. Here, we showed that the T‐cell responses of individuals who underwent booster vaccination with CoronaVac were largely protective against the SARS‐CoV‐2 Omicron spike protein. To specifically estimate the impact of Omicron mutations on vaccinated participants, 16 peptides derived from the spike protein of the ancestral virus or Omicron strain with mutations were used to stimulate peripheral blood mononuclear cells (PBMCs) from the volunteers. Compared with the administration of two doses of vaccine, booster vaccination substantially enhanced T‐cell activation in response to both the ancestral and Omicron epitopes, although the enhancement was slightly weakened by the Omicron mutations. Then, the peptides derived from these spike proteins were used separately to stimulate PBMCs. Interestingly, compared with the ancestral peptides, only the peptides with the G339D or N440K mutation were detected to significantly destabilize the T‐cell response. Although more participants need to be evaluated to confirm this conclusion, our study nonetheless estimates the impacts of mutations on T‐cell responses to the SARS‐CoV‐2 Omicron variant.

The humoral and cellular immune response of a third dose adenoviral-based vectored vaccine after a single or 2 shots of inactivated COVID-19 vaccine in healthy adults

“…Our results were similar to previous research, which indicated that boosting ChAdOx1 after completing 2 shots of CoronaVac elicited a higher number of RBD-specific IgG than those without the boosting [5]. Several studies found that three doses of inactivated or mRNA vaccine resulted in a more significant immunogenic response than two doses [13, 14].…”

The outbreak of SARS‐CoV‐2 Omicron lineages, immune escape, and vaccine effectivity

“… 81 Similarly, several studies predicted that the memory mediated by T cells in individuals with prior infection (WT or previous VOCs) and vaccination (with EMA‐approved vaccines) has preserved reactivity to the Omicron variant, especially their reactivity is enhanced by booster vaccination. 82 , 83 , 84 , 85 , 86 , 87 Surprisingly, the percentage of participants with prior infection and/or vaccination had a >50% reduction in T‐cell response to Omicron spike was higher than Delta (21.2% vs. 9.7%), potentially due to escape of HLA‐I restricted epitopes. 83 ” Therefore, it is important to understand protection against these VOCs may be hidden in cross‐reactive SARS‐CoV‐2‐specific T‐cell mediated immunity.…”

Advances in Research on COVID-19 Vaccination for People Living with HIV

“…It is yet to discover what level of immunity is required to prevent hospitalization and death, but real-world data suggest that vaccination is successful in preventing these even in the presence of transmissible and virulent variants of concern (VOCs). [ 56 , 76 ] In the future, repeated boosting might be necessary to maintain long-term immunological memory of SARS-CoV-2 and VOCs, especially for immunocompromised populations such as PLWH. Therefore, there is a need to increase the surveillance of the virus so that effective measures can be taken promptly.…”