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Microorganisms
Volume 13
Issue 7
10.3390/microorganisms13071649
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Surface Display of Avian H5 and H9 Hemagglutinin Antigens on Non-Genetically Modified Lactobacillus Cells for Bivalent Oral AIV Vaccine Development

by
Fuyi Liu
1,2,†,
Jingbo Chang
1,2,†,
Jingqi Huang
1,2,
Yuping Liao
1,
Xiaonan Deng
1,
Tingting Guo
1,
Jian Kong
1,* and
Wentao Kong
1,*
1
State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China
2
School of Life Sciences, Shandong University, Qingdao 266237, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Microorganisms 2025, 13(7), 1649; https://doi.org/10.3390/microorganisms13071649
Submission received: 31 May 2025 / Revised: 2 July 2025 / Accepted: 8 July 2025 / Published: 11 July 2025
(This article belongs to the Section Food Microbiology)
Versions Notes

Abstract

A novel bivalent oral vaccine candidate against H5N1 and H9N2 avian influenza virus (AIV) was developed using Lactobacillus surface display technology without genetic modification. The hemagglutinin subunit 1 (HA1) antigens from both subtypes were fused to the surface layer-binding domain of Lactobacillus crispatus K313, expressed in Escherichia coli, and purified. Wild-type Lactobacillus johnsonii H31, isolated from chicken intestine, served as a delivery vehicle by adsorbing and stably displaying the HA1 proteins on its surface. This approach eliminates the need for bacterial engineering while utilizing lactobacilli’s natural capacity to protect surface-displayed antigens, as evidenced by HA1’s protease resistance. Mouse immunization studies demonstrated induction of strong systemic IgG and mucosal IgA responses against both H5N1 and H9N2 HA1. The system offers several advantages, including safety through non-GMO probiotics, potential for multivalent vaccine expansion, and intrinsic antigen protection by lactobacilli. These findings suggest this platform could enable development of cost-effective, multivalent AIV vaccines.
Keywords: Lactobacillus; oral vaccine; non-genetically modified organism; surface display Lactobacillus; oral vaccine; non-genetically modified organism; surface display

Share and Cite

MDPI and ACS Style

Liu, F.; Chang, J.; Huang, J.; Liao, Y.; Deng, X.; Guo, T.; Kong, J.; Kong, W. Surface Display of Avian H5 and H9 Hemagglutinin Antigens on Non-Genetically Modified Lactobacillus Cells for Bivalent Oral AIV Vaccine Development. Microorganisms 2025, 13, 1649. https://doi.org/10.3390/microorganisms13071649

AMA Style

Liu F, Chang J, Huang J, Liao Y, Deng X, Guo T, Kong J, Kong W. Surface Display of Avian H5 and H9 Hemagglutinin Antigens on Non-Genetically Modified Lactobacillus Cells for Bivalent Oral AIV Vaccine Development. Microorganisms. 2025; 13(7):1649. https://doi.org/10.3390/microorganisms13071649

Chicago/Turabian Style

Liu, Fuyi, Jingbo Chang, Jingqi Huang, Yuping Liao, Xiaonan Deng, Tingting Guo, Jian Kong, and Wentao Kong. 2025. "Surface Display of Avian H5 and H9 Hemagglutinin Antigens on Non-Genetically Modified Lactobacillus Cells for Bivalent Oral AIV Vaccine Development" Microorganisms 13, no. 7: 1649. https://doi.org/10.3390/microorganisms13071649

APA Style

Liu, F., Chang, J., Huang, J., Liao, Y., Deng, X., Guo, T., Kong, J., & Kong, W. (2025). Surface Display of Avian H5 and H9 Hemagglutinin Antigens on Non-Genetically Modified Lactobacillus Cells for Bivalent Oral AIV Vaccine Development. Microorganisms, 13(7), 1649. https://doi.org/10.3390/microorganisms13071649

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