ポスト・オミクロン時代におけるヒト免疫系の進化(Evolution of the human immune system in the post-Omicron era)

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2024-01-12 韓国基礎科学研究院(IBS)Figure 1. Immunological role of the neutralizing antibodies and memory T cells
Figure 1. Immunological role of the neutralizing antibodies and memory T cells
Neutralizing antibodies and memory T cells are two components of adaptive immunity conferred by viral infection or vaccination. Neutralizing antibodies physically bind to viruses to block them from infecting the cells. While T cells cannot prevent the viral infection, they can effectively search and destroy cells that display viral antigens on their surface, eliminating them to prevent further infection.

◆COVID-19のパンデミックから4年が経過し、SARS-CoV-2は撲滅されず、新たな変異株が継続的に出現しています。ワクチン接種が進んでいるにもかかわらず、新たな変異株によるワクチン接種後感染が一般的であり、人間の免疫応答も変化していることが新しい研究で示唆されています。
◆韓国の研究チームは、Omicron変異株によるワクチン接種後感染を経た患者のメモリーT細胞が、将来のOmicron変異株に対して強化された免疫を獲得することを発見しました。この研究により、Omicron感染を経験することで、将来の変異株による重症なCOVID-19症状を回避できる可能性が示唆されています。

<関連情報>

オミクロンBA.2の感染により、後のオミクロン亜型のスパイクを認識するCD8+ T細胞応答が誘発される。 Omicron BA.2 breakthrough infection elicits CD8+ T cell responses recognizing the spike of later Omicron subvariants

Sang-Hoon Kim, Jihye Kim, Sungmin Jung, Ji Yun,
Science Immunology  Published:19 Jan 2024
DOI:https://doi.org/10.1126/sciimmunol.ade6132

Editor’s summary

Recent studies have suggested that memory T cells play a critical role in protecting individuals immunized with SARS-CoV-2 vaccines against variants. Kim et al. tracked memory T cell responses in a cohort of vaccinated individuals in Korea who experienced breakthrough Omicron subvariant infection. They confirmed that BNT162b2 vaccination induced memory CD4+ and CD8+ T cells specific to BA.4/BA.5 spike, even if these individuals had a prior SARS-CoV-2 infection. Breakthrough infection with early Omicron subvariants (BA.1/BA.2) induced an increase in cross-reactive CD8+ T cell responses specific to BA.4/BA.5 spike. They identified peptides in the BA.2 spike that were fully conserved in BA.4/BA.5 and later subvariants but absent in original spike. Together, these findings provide further evidence that breakthrough infection can induce cross-reactive memory T cell responses that contribute to protection against newly emerging SARS-CoV-2 subvariants. —Christiana Fogg

Abstract

Here, we examine peripheral blood memory T cell responses against the SARS-CoV-2 BA.4/BA.5 variant spike among vaccinated individuals with or without Omicron breakthrough infections. We provide evidence supporting a lack of original antigenic sin in CD8+ T cell responses targeting the spike. We show that BNT162b2-induced memory T cells respond to the BA.4/BA.5 spike. Among individuals with BA.1/BA.2 breakthrough infections, IFN-γ–producing CD8+ T cell responses against the BA.4/BA.5 spike increased. In a subgroup with BA.2 breakthrough infections, IFN-γ–producing CD8+ T cell responses against the BA.2-mutated spike region increased and correlated directly with responses against the BA.4/BA.5 spike, indicating that BA.2 spike–specific CD8+ T cells elicited by BA.2 breakthrough infection cross-react with the BA.4/BA.5 spike. We identified CD8+ T cell epitope peptides that are present in the spike of BA.2 and BA.4/BA.5 but not the original spike. These peptides are fully conserved in the spike of now-dominant XBB lineages. Our study shows that breakthrough infection by early Omicron subvariants elicits CD8+ T cell responses that recognize epitopes within the spike of newly emerging subvariants.

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