A synthetic TLR4 agonist significantly increases humoral immune responses and the protective ability of an MDCK-cell-derived inactivated H7N9 vaccine in mice

Antigenically divergent H7N9 viruses pose a potential threat to public health, with the poor immunogenicity of candidate H7N9 vaccines demonstrated in clinical trials underscoring the urgent need for more-effective H7N9 vaccines. In the present study, mice were immunized with various doses of a susp...

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Published in:Archives of virology 2024-08, Vol.169 (8), p.163, Article 163
Main Authors: Luo, Jian, Zhang, Min, Ye, Qian, Gao, Feixia, Xu, Wenting, Li, Beibei, Wang, Qi, Zhao, Liang, Tan, Wen-Song
Format: Article
Language:English
Subjects:
Adjuvants
Agonists
Biomedical and Life Sciences
Biomedicine
Clinical trials
Cross-protection
Exo-a-sialidase
Hemagglutination
Immune response (humoral)
Immunity
Immunogenicity
Immunoglobulin G
Infectious Diseases
Influenza
Medical Microbiology
Original Article
Public health
TLR4 protein
Toll-like receptors
Vaccine efficacy
Vaccines
Virology
Viruses
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Summary:Antigenically divergent H7N9 viruses pose a potential threat to public health, with the poor immunogenicity of candidate H7N9 vaccines demonstrated in clinical trials underscoring the urgent need for more-effective H7N9 vaccines. In the present study, mice were immunized with various doses of a suspended-MDCK-cell-derived inactivated H7N9 vaccine, which was based on a low-pathogenic H7N9 virus, to assess cross-reactive immunity and cross-protection against antigenically divergent H7N9 viruses. We found that the CRX-527 adjuvant, a synthetic TLR4 agonist, significantly enhanced the humoral immune responses of the suspended-MDCK-cell-derived H7N9 vaccine, with significant antigen-sparing and immune-enhancing effects, including robust virus-specific IgG, hemagglutination-inhibiting (HI), neuraminidase-inhibiting (NI), and virus-neutralizing (VN) antibody responses, which are crucial for protection against influenza virus infection. Moreover, the CRX-527-adjuvanted H7N9 vaccine also elicited cross-protective immunity and cross-protection against a highly pathogenic H7N9 virus with a single vaccination. Notably, NI and VN antibodies might play an important role in cross-protection against lethal influenza virus infections. This study showed that a synthetic TLR4 agonist adjuvant has a potent immunopotentiating effect, which might be considered worth further development as a means of increasing vaccine effectiveness.
ISSN:0304-8608
1432-8798
1432-8798
DOI:10.1007/s00705-024-06082-8