Advanced search
1 file | 928.61 KB Add to list

Intranodal administration of mRNA encoding nucleoprotein provides cross-strain immunity against influenza in mice

Author
Organization
Abstract
Background: Current human influenza vaccines lack the adaptability to match the mutational rate of the virus and therefore require annual revisions. Because of extensive manufacturing times and the possibility that antigenic alterations occur during viral vaccine strain production, an inherent risk exists for antigenic mismatch between the new influenza vaccine and circulating viruses. Targeting more conserved antigens such as nucleoprotein (NP) could provide a more sustainable vaccination strategy by inducing long term and heterosubtypic protection against influenza. We previously demonstrated that intranodal mRNA injection can induce potent antigen-specific T-cell responses. In this study, we investigated whether intranodal administration of mRNA encoding NP can induce T-cell responses capable of protecting against a heterologous influenza virus challenge. Methods: BALB/c mice were immunized in the inguinal lymph nodes with different vaccination regimens of mRNA encoding NP. Immune responses were compared with NP DNA vaccination via IFN-gamma ELISPOT and in vivo cytotoxicity. For survival experiments, mice were prime-boost vaccinated with 17 mu g NP mRNA and infected with 1LD50 of H1N1 influenza virus 8weeks after boost. Weight was monitored and viral titers, cytokines and immune cell populations in the bronchoalveolar lavage, and IFN-gamma responses in the spleen were analyzed. Results: Our results demonstrate that NP mRNA induces superior systemic T-cell responses against NP compared to classical DNA vaccination. These responses were sustained for several weeks even at low vaccine doses. Upon challenge infection, vaccination with NP mRNA resulted in reduced lung viral titers and improved recovery from infection. Finally, we show that vaccination with NP mRNA affects the immune response in infected lungs by lowering immune cell infiltration while increasing the fraction of T cells, monocytes and MHC II+ alveolar macrophages within immune infiltrates. This change was associated with altered levels of both pro- and anti-inflammatory cytokines. Conclusions: These findings suggest that intranodal vaccination with NP mRNA induces cross-strain immunity against influenza, but also highlight a paradox of influenza immunity, whereby robust immune responses can provide protection, but can also transiently exacerbate symptoms during infection.
Keywords
mRNA, Influenza, Universal vaccine, Intranodal, Nucleoprotein, T cell, CD8(+) T-CELLS, A VIRUS-INFECTION, DNA VACCINATION, DENDRITIC CELLS, PLASMID DNA, PRECLINICAL EVALUATION, PROTECTIVE EFFICACY, VACCINES, INJECTION, RECOGNITION

Downloads

  • 12967 2019 Article 1991.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 928.61 KB

Citation

Please use this url to cite or link to this publication:

MLA
Joe, Patrick Tjok, et al. “Intranodal Administration of MRNA Encoding Nucleoprotein Provides Cross-Strain Immunity against Influenza in Mice.” JOURNAL OF TRANSLATIONAL MEDICINE, vol. 17, 2019.
APA
Joe, P. T., Christopoulou, I., Van Hoecke, L., Schepens, B., Ysenbaert, T., Heirman, C., … Aerts, J. (2019). Intranodal administration of mRNA encoding nucleoprotein provides cross-strain immunity against influenza in mice. JOURNAL OF TRANSLATIONAL MEDICINE, 17.
Chicago author-date
Joe, Patrick Tjok, Ioanna Christopoulou, Lien Van Hoecke, Bert Schepens, Tine Ysenbaert, Carlo Heirman, Kris Thielemans, Xavier Saelens, and Joeri Aerts. 2019. “Intranodal Administration of MRNA Encoding Nucleoprotein Provides Cross-Strain Immunity against Influenza in Mice.” JOURNAL OF TRANSLATIONAL MEDICINE 17.
Chicago author-date (all authors)
Joe, Patrick Tjok, Ioanna Christopoulou, Lien Van Hoecke, Bert Schepens, Tine Ysenbaert, Carlo Heirman, Kris Thielemans, Xavier Saelens, and Joeri Aerts. 2019. “Intranodal Administration of MRNA Encoding Nucleoprotein Provides Cross-Strain Immunity against Influenza in Mice.” JOURNAL OF TRANSLATIONAL MEDICINE 17.
Vancouver
1.
Joe PT, Christopoulou I, Van Hoecke L, Schepens B, Ysenbaert T, Heirman C, et al. Intranodal administration of mRNA encoding nucleoprotein provides cross-strain immunity against influenza in mice. JOURNAL OF TRANSLATIONAL MEDICINE. 2019;17.
IEEE
[1]
P. T. Joe et al., “Intranodal administration of mRNA encoding nucleoprotein provides cross-strain immunity against influenza in mice,” JOURNAL OF TRANSLATIONAL MEDICINE, vol. 17, 2019.
@article{8631740,
  abstract     = {Background: Current human influenza vaccines lack the adaptability to match the mutational rate of the virus and therefore require annual revisions. Because of extensive manufacturing times and the possibility that antigenic alterations occur during viral vaccine strain production, an inherent risk exists for antigenic mismatch between the new influenza vaccine and circulating viruses. Targeting more conserved antigens such as nucleoprotein (NP) could provide a more sustainable vaccination strategy by inducing long term and heterosubtypic protection against influenza. We previously demonstrated that intranodal mRNA injection can induce potent antigen-specific T-cell responses. In this study, we investigated whether intranodal administration of mRNA encoding NP can induce T-cell responses capable of protecting against a heterologous influenza virus challenge.
Methods: BALB/c mice were immunized in the inguinal lymph nodes with different vaccination regimens of mRNA encoding NP. Immune responses were compared with NP DNA vaccination via IFN-gamma ELISPOT and in vivo cytotoxicity. For survival experiments, mice were prime-boost vaccinated with 17 mu g NP mRNA and infected with 1LD50 of H1N1 influenza virus 8weeks after boost. Weight was monitored and viral titers, cytokines and immune cell populations in the bronchoalveolar lavage, and IFN-gamma responses in the spleen were analyzed.
Results: Our results demonstrate that NP mRNA induces superior systemic T-cell responses against NP compared to classical DNA vaccination. These responses were sustained for several weeks even at low vaccine doses. Upon challenge infection, vaccination with NP mRNA resulted in reduced lung viral titers and improved recovery from infection. Finally, we show that vaccination with NP mRNA affects the immune response in infected lungs by lowering immune cell infiltration while increasing the fraction of T cells, monocytes and MHC II+ alveolar macrophages within immune infiltrates. This change was associated with altered levels of both pro- and anti-inflammatory cytokines.
Conclusions: These findings suggest that intranodal vaccination with NP mRNA induces cross-strain immunity against influenza, but also highlight a paradox of influenza immunity, whereby robust immune responses can provide protection, but can also transiently exacerbate symptoms during infection.},
  articleno    = {242},
  author       = {Joe, Patrick Tjok and Christopoulou, Ioanna and Van Hoecke, Lien and Schepens, Bert and Ysenbaert, Tine and Heirman, Carlo and Thielemans, Kris and Saelens, Xavier and Aerts, Joeri },
  issn         = {1479-5876},
  journal      = {JOURNAL OF TRANSLATIONAL MEDICINE},
  keywords     = {mRNA,Influenza,Universal vaccine,Intranodal,Nucleoprotein,T cell,CD8(+) T-CELLS,A VIRUS-INFECTION,DNA VACCINATION,DENDRITIC CELLS,PLASMID DNA,PRECLINICAL EVALUATION,PROTECTIVE EFFICACY,VACCINES,INJECTION,RECOGNITION},
  language     = {eng},
  pages        = {14},
  title        = {Intranodal administration of mRNA encoding nucleoprotein provides cross-strain immunity against influenza in mice},
  url          = {http://dx.doi.org/10.1186/s12967-019-1991-3},
  volume       = {17},
  year         = {2019},
}

Altmetric
View in Altmetric
Web of Science
Times cited: