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Arch Virol . A synthetic TLR4 agonist significantly increases humoral immune responses and the protective ability of an MDCK-cell-derived inactivat

tetano

Editor, Senior Moderator
Arch Virol


. 2024 Jul 11;169(8):163.
doi: 10.1007/s00705-024-06082-8. A synthetic TLR4 agonist significantly increases humoral immune responses and the protective ability of an MDCK-cell-derived inactivated H7N9 vaccine in mice

Jian Luo[SUP] 1 2 [/SUP], Min Zhang[SUP] 2 [/SUP], Qian Ye[SUP] 1 [/SUP], Feixia Gao[SUP] 2 [/SUP], Wenting Xu[SUP] 2 [/SUP], Beibei Li[SUP] 2 [/SUP], Qi Wang[SUP] 2 [/SUP], Liang Zhao[SUP] 1 [/SUP], Wen-Song Tan[SUP] 3 [/SUP]



Affiliations
Abstract

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.


 
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