In a groundbreaking study published in the journal Cell Host & Microbe, researchers have made an exciting discovery regarding the lasting T-cell immunity in healthcare workers against SARS-CoV-2 variants. The study focuses on the response of T-cells to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shedding light on their ability to recognize and combat different variants of the virus.
The importance of sustained, cross-reactive immune memory cannot be emphasized enough in protecting individuals from severe outcomes during the ongoing COVID-19 pandemic. As the virus continues to evolve, multiple SARS-CoV-2 variants have emerged, including the Omicron XBB sublineages. Notably, the Omicron BA.2.86 subvariant has been classified as a variant under monitoring by the World Health Organization due to its hypermutated state.
Reports have indicated significant immune evasion by the BA.2.86 variant, which raises concerns about the efficacy of spike-specific T-cells in recognizing this variant. While previous studies have demonstrated that T-cell responses against the ancestral strain are cross-reactive against the Omicron BA.1 variant, it remains crucial to determine whether BA.2.86 mutations hinder the recognition of this variant by memory T-cells.
The study titled Post-pandemic memory T cell response to SARS-CoV-2 is durable, broadly targeted, and cross-reactive to the hypermutated BA.2.86 variant aimed to assess the durability and cross-reactivity of SARS-CoV-2 spike-specific memory T-cell responses. The researchers included thirty-nine healthcare workers with a history of vaccination and infection in their investigation. The participants provided blood samples in mid-late 2023, with varying vaccination history and exposure to different variants of the virus.
The researchers measured cytokine production in response to spike peptide pools of the ancestral strain, as well as the BA.1, BA.2.86, and XBB.1 variants. Interestingly, approximately 95% of the participants exhibited a robust T-cell response to the ancestral spike protein even after 1.5 years since their last infection.
The study revealed that the CD4+ T-cell response was preserved against Omicron variants, whereas the proportion of CD8+ T-cells to the ancestral spike protein was lower but consistent across the different variants. Notably, some participants who lacked a CD8 response to the ancestral spike gained CD8 responses against at least one Omicron variant.
Furthermore, the study identified T-cell responses to nucleocapsid and membrane (N & M) proteins in 35 participants. Most subjects demonstrated CD4 responses to both N & M and spike proteins, while CD8 responders were distributed among those targeting both, exclusively N & M, and spike only.
To assess T-cell maintenance, the researchers compared spike- and N & M-specific T-cell frequencies in paired samples obtained at two time points: prior to the BA.1 wave and approximately 1.5 years later. The results showed that spike-specific CD4+ T-cell frequency remained relatively stable over time. Moreover, all participants without a CD4 response to N & M exhibited a CD4 response by the later time point.
The evolution of CD8 responses varied among participants, with some showing sustained, lost, or newly acquired responses. The study also identified four spike-specific memory T-cell subsets: naïve, early differentiated, late differentiated, and effector. Overall, the findings indicate robust memory T-cell responses in healthcare workers even more than 1.5 years after the Omicron wave. These T-cell responses may be attributed to recurrent exposure to SARS-CoV-2, expanding the T-cell memory pool, or the presence of durable responses from prior infection and vaccination.
The results of this study provide valuable insights into T-cell immunity against SARS-CoV-2 variants. The maintenance of T-cell responses and their ability to recognize highly mutated variants highlight the potential for hybrid immunity and the accumulation of spike- and non-spike-specific T-cells. As the world continues to navigate the challenges of the COVID-19 pandemic, these findings contribute to our understanding of immune responses and may aid in the development of more effective vaccines and therapeutic interventions.
Journal reference: Nesamari R, Omondi MA, Baguma R, et al. Post-pandemic memory T-cell response to SARS-CoV-2 is durable, broadly targeted, and cross-reactive to the hypermutated BA.2.86 variant. Cell Host & Microbe, 2024, DOI: 10.1016/j.chom.2023.12.003.
