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. 2024 Mar 13;12(3):300.
doi: 10.3390/vaccines12030300.

Influenza a Neuraminidase-Based Bivalent mRNA Vaccine Induces Th1-Type Immune Response and Provides Protective Effects in Mice

Mingyang Li  1 , Mengyuan Liu  1 , Shaohui Song  1 , Ruirui Zhao  1 , Yun Xie  1 , Jing Liu  1 , Lilan Xu  1 , Xuefeng Ma  1 , Mingyu Song  1 , Jian Zhou  1 , Guoyang Liao  1
Affiliations

Influenza a Neuraminidase-Based Bivalent mRNA Vaccine Induces Th1-Type Immune Response and Provides Protective Effects in Mice

Mingyang Li et al. Vaccines (Basel). .

Abstract

Vaccines are one of the most effective means of preventing influenza A, typically containing the hemagglutinin (HA) of the influenza A virus. However, antigenic drift and shift of the influenza A virus can lead to instability in vaccine efficacy. Compared to HA, the antigenic variation rate of neuraminidase (NA) is slower. In traditional inactivated influenza vaccines, although they contain a certain amount of NA, there are significant differences between different batches, which cannot consistently induce NA-based immune responses. Therefore, NA is often overlooked in vaccine development. In this study, we report an mRNA vaccine encoding the NA of two strains of influenza A virus. The experimental results demonstrated that when matched with the viral strain, this mRNA vaccine induced high levels of neutralizing antibodies, providing a protective effect to mice in viral challenge experiments, and this immune response was shown to be biased towards the Th1 type. In summary, this study demonstrates that NA is a promising potential antigen, providing new insights for the development of influenza A virus vaccines.

Keywords: Th1; influenza A; mRNA vaccine; neuraminidase.

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Conflict of interest statement

The authors have no conflicts of interest.

Figures

Figure 1
Figure 1
Influenza A N1 + N2 mRNA vaccine design. N1: A/Michigan/45/2015 (H1N1)-NA (green); N2: A/Hong Kong/4801/2014 (H3N2)-NA (yellow).
Figure 2
Figure 2
Induction of specific neutralizing antibodies by the Influenza A N1 + N2 mRNA vaccine. (A). Neutralizing activity of mouse sera from Influenza A N1 + N2 mRNA-immunized mice against A/Michigan/45/2015 (H1N1). (B). Neutralizing activity of mouse sera from Influenza A N1 + N2 mRNA-immunized mice against A/Hong Kong/4801/2014 (H3N2). ** p < 0.01.
Figure 3
Figure 3
Protective effect of the Influenza A N1 + N2 mRNA vaccine in viral challenge experiments. (A). Statistical analysis of mouse body weight changes in the A/Michigan/45/2015 (H1N1) viral cha −lenge experiment. (B). KM curve analysis of mouse survival in the A/Michigan/45/2015 (H1N1) viral challenge experiment. (C). Statistical analysis of mouse body weight changes in the A/Hong Kong/4801/2014 (H3N2) viral challenge experiment. (D). KM curve analysis of mouse survival in the A/Hong Kong/4801/2014 (H3N2) viral challenge experiment. * p < 0.05, ** p < 0.01, and *** p < 0.001.
Figure 4
Figure 4
Influenza A N1 + N2 mRNA vaccine stimulates the production of different types of cytkines by splenic lymphocytes. (A). IFN−γ: Elispot assay (top), spot count bar graph (bottom). (B). IL−4: Elispot assay (top), spot count bar graph (bottom). (C). Flow cytometry analysis of the ratio of Th1 and Th2 cells. ** p < 0.01, and *** p < 0.001.
Figure 4
Figure 4
Influenza A N1 + N2 mRNA vaccine stimulates the production of different types of cytkines by splenic lymphocytes. (A). IFN−γ: Elispot assay (top), spot count bar graph (bottom). (B). IL−4: Elispot assay (top), spot count bar graph (bottom). (C). Flow cytometry analysis of the ratio of Th1 and Th2 cells. ** p < 0.01, and *** p < 0.001.
Figure 5
Figure 5
Influenza A N1 + N2 mRNA vaccine stimulates the production of different types of IgG antibodies. (A). ELISA assay determining the titers of IgG2a and IgG1 antibodies against NA in the serum of immunized mice. (B). Ratio of IgG2a to IgG1 antibodies against NA in the serum of immunized mice. * p < 0.05, and ** p < 0.01.
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