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

• DOI: 10.1038/s41392-024-01906-0
• Publication Date: 2024-07-22T04:01:52Z
• 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
• Keywords: Immunoglobulin A

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