System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Research Support, Non-U.S. Gov't Epublish 6 citations

PubMed: 39039046 DOI: 10.1038/s41392-024-01906-0

Intranasal adenovirus-vectored Omicron vaccine induced nasal immunoglobulin A has superior neutralizing potency than serum antibodies.

Signal Transduct Target Ther 9(1):190

Authors: Si Chen, Zhengyuan Zhang, Qian Wang, Qi Yang, Li Yin, Lishan Ning, Zhilong Chen, Jielin Tang, Weiqi Deng, Ping He, Hengchun Li, Linjing Shi, Yijun Deng, Zijian Liu, Hemeng Bu, Yaohui Zhu, Wenming Liu, Linbing Qu, Liqiang Feng, Xiaoli Xiong, Baoqing Sun, Nanshan Zhong, Feng Li, Pingchao Li, Xinwen Chen, Ling Chen

Affiliations

  • Guangzhou Institute of Infectious Disease, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
  • Guangzhou National Laboratory, Guangzhou, China.
  • State Key Laboratory of Respiratory Disease, Center for Cell Lineage Research, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • University of Chinese Academy of Sciences, Beijing, China.
  • State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • Xiamen United Institute of Respiratory Health, Xiamen, China.
  • State Key Laboratory of Respiratory Disease, Center for Cell Lineage Research, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Guangzhou National Laboratory, Guangzhou, China.
  • State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • Guangzhou Institute of Infectious Disease, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
  • Guangzhou National Laboratory, Guangzhou, China.
  • State Key Laboratory of Respiratory Disease, Center for Cell Lineage Research, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Abstract

The upper respiratory tract is the initial site of SARS-CoV-2 infection. Nasal spike-specific secretory immunoglobulin A (sIgA) correlates with protection against Omicron breakthrough infection. We report that intranasal vaccination using human adenovirus serotype 5 (Ad5) vectored Omicron spike in people who previously vaccinated with ancestral vaccine could induce robust neutralizing sIgA in the nasal passage. Nasal sIgA was predominantly present in dimeric and multimeric forms and accounted for nearly 40% of total proteins in nasal mucosal lining fluids (NMLFs). A low-level IgG could also be detected in NMLFs but not IgM, IgD, and IgE. After a complete nasal wash, sIgA in the nasal passage could be replenished rapidly within a few hours. A comparison of purified paired serum IgA, serum IgG, and nasal sIgA from the same individuals showed that sIgA was up to 3-logs more potent than serum antibodies in binding to spikes and in neutralizing Omicron subvariants. Serum IgG and IgA failed to neutralize XBB and BA.2.86, while nasal sIgA retained potent neutralization against these newly emerged variants. Further analysis showed that sIgA was more effective than IgG or IgA in blocking spike-mediated cell-to-cell transmission and protecting hACE2 mice from XBB challenge. Using a sIgA monoclonal antibody as a reference, we estimated that the total nasal sIgA contains about 2.6-3.9% spike-specific sIgA in NMLFs collected approximately one month after intranasal vaccination. Our study provided insights for developing intranasal vaccines that can induce sIgA to build an effective and mutation-resistant first-line immune barrier against constantly emerging variants.

MeSH

Cells, Serum, Vaccines, Antibodies, Adenoviridae, Immunoglobulins, Vaccination, Immunoglobulin A, Immunoglobulin A, Secretory, Signal Transduction, Infections

Cited by