Boost immunizations with NA-derived peptide conjugates achieve induction of NA inhibition antibodies and heterologous influenza protections
De-Jian Liu,
Cui-Cui Liu,
Xiu-Qin Zhong,
Xuan Wu,
Hui-Hui Zhang,
Shang-Wen Lu,
Zhuo-Ling Shen,
Wen-Wen Song,
Shi-Long Zhao,
You-Song Peng,
He-Ping Zheng,
Mu-Yang Wan,
Yao-Qing Chen,
Lei Deng
Affiliations
De-Jian Liu
Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China
Cui-Cui Liu
Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China
Xiu-Qin Zhong
Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China
Xuan Wu
Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China
Hui-Hui Zhang
Bioinformatics Center, College of Biology, Hunan University, Changsha 410082, China
Shang-Wen Lu
Bioinformatics Center, College of Biology, Hunan University, Changsha 410082, China
Zhuo-Ling Shen
Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China
Wen-Wen Song
Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China
Shi-Long Zhao
Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China
You-Song Peng
Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China; Bioinformatics Center, College of Biology, Hunan University, Changsha 410082, China
He-Ping Zheng
Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China; Bioinformatics Center, College of Biology, Hunan University, Changsha 410082, China
Mu-Yang Wan
Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China
Yao-Qing Chen
School of Public Health (Shenzhen), Sun Yat-Sen University, Shenzhen, Guangdong Province 518107, China
Lei Deng
Hunan Provincial Key Laboratory of Medical Virology, College of Biology, Hunan University, Changsha 410082, China; Bioinformatics Center, College of Biology, Hunan University, Changsha 410082, China; Beijing Weimiao Biotechnology Co., Ltd., Haidian District, Beijing 100000, China; Corresponding author
Summary: Neuraminidase is suggested as an important component for developing a universal influenza vaccine. Targeted induction of neuraminidase-specific broadly protective antibodies by vaccinations is challenging. To overcome this, we rationally select the highly conserved peptides from the consensus amino acid sequence of the globular head domains of neuraminidase. Inspired by the B cell receptor evolution process, a reliable sequential immunization regimen is designed to result in immuno-focusing by steering bulk immune responses to a selected region where broadly protective B lymphocyte epitopes reside. After priming neuraminidase protein-specific antibody responses in C57BL/6 or BALB/c inbred mice strains by immunization or pre-infection, boost immunizations with certain neuraminidase-derived peptide-keyhole limpet hemocyanin conjugates significantly strengthened serum neuraminidase inhibition activities and cross-protections. Overall, this study provides proof of concept for a peptide-based sequential immunization strategy for achieving targeted induction of cross-protective antibody response, which provides references for designing universal vaccines against other highly variable pathogens.
