Breakthrough infection evokes the nasopharyngeal innate immune responses established by SARS-CoV-2-inactivated vaccine

He, Xiaomeng1; Cao, Yingyin1; Lu, Yanmei1; Qi, Furong1; Wang, Haiyan1; Liao, Xuejiao1; Xu, Gang1; Yang, Biao1; Ma, Junhua1; Li, Dapeng1; Tang, Xian1; Zhang, Zheng1,2

2023-06-29

10.3389/fimmu.2023.1181121

FRONTIERS IN IMMUNOLOGY   影响因子和分区

1664-3224

Nasopharyngeal immune responses are vital for defense against SARS-CoV-2 infection. Although vaccination via muscle immunization has shown a high efficacy in reducing severity and death in COVID-19 infection, breakthrough infection frequently happens because of mutant variants and incompletely established mucosal immunity, especially in the upper respiratory tract. Here, we performed a single-cell RNA and T-cell receptor repertoire sequencing and delineated a high-resolution transcriptome landscape of nasopharyngeal mucosal immune and epithelial cells in vaccinated persons with breakthrough infection and non-vaccinated persons with natural infection as control. The epithelial cells showed anti-virus gene expression diversity and potentially recruited innate immune cells into the nasopharyngeal mucous of vaccinated patients. Upon infection, they released significant pro-inflammatory cytokines and chemokines by macrophages and monocytes and expressed antigen-presenting relevant genes by dendritic cells. Such immune responses of nasopharyngeal innate immune cells would facilitate the strengthened expression of cytotoxic genes in virus-specific T-cell or B-cell differentiation into antibody-secreting cells at the early stage of breakthrough infection through cell interaction between innate and adaptive immune cells. Notably, these alterations of nasopharyngeal immune cells in breakthrough infection depended on the activated Nuclear factor-& kappa;B (NF-& kappa;B) and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) signaling rather than type I interferon responses due to the general reduction in interferon-stimulated gene expression. Our findings suggest that vaccination potentially strengthens innate immune barriers and virus-specific memory immune cell responses, which could be quickly activated to defend against variant breakthrough infection and maintain nasopharyngeal epithelial cell integrity. Thus, this study highlights the necessity of a boost via nasal mucous after intramuscular immunization.

SARS-CoV-2 breakthrough infection mucosal immunity single-cell RNA sequencing innate immune memory

SCI

英语

第一 ; 通讯

National Natural Science Foundation of China["81901616","92169204","82025022"] ; National Science and Technology Major Project of the Etiology and Epidemic Prevention Technology System[2022YFC2304503] ; Guangdong Basic and Applied Basic Research Foundation[2023A1515010756] ; Science and Technology General Program and Innovation Committee of Shenzhen Municipality["JCYJ20220530163409023","JSGG20220226085550001"] ; Shenzhen Science and Technology Program[ZDSYS20210623091810030] ; Central Charity Fund of Chinese Academy of Medical Science[JSGG20220606140200002] ; Science and Technology Innovation Committee of Shenzhen Municipality[SRPG22-006] ; null[2020-PT310-009]

Immunology

Immunology

WOS:001028202700001

FRONTIERS MEDIA SA

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Affiliated Hosp 2, Inst Hepatol,Natl Clin Res Ctr Infect Dis,Sch Med, Shenzhen, Guangdong, Peoples R China
2.Chinese Acad Med Sci, Shenzhen Res Ctr Communicable Dis Diag & Treatment, Shenzhen, Guangdong, Peoples R China

He, Xiaomeng,Cao, Yingyin,Lu, Yanmei,et al. Breakthrough infection evokes the nasopharyngeal innate immune responses established by SARS-CoV-2-inactivated vaccine[J]. FRONTIERS IN IMMUNOLOGY,2023,14.

He, Xiaomeng.,Cao, Yingyin.,Lu, Yanmei.,Qi, Furong.,Wang, Haiyan.,...&Zhang, Zheng.(2023).Breakthrough infection evokes the nasopharyngeal innate immune responses established by SARS-CoV-2-inactivated vaccine.FRONTIERS IN IMMUNOLOGY,14.

He, Xiaomeng,et al."Breakthrough infection evokes the nasopharyngeal innate immune responses established by SARS-CoV-2-inactivated vaccine".FRONTIERS IN IMMUNOLOGY 14(2023).