Molecular Events in Immune Responses to Sublingual Influenza Vaccine with Hemagglutinin Antigen and Poly(I:C) Adjuvant in Nonhuman Primates, Cynomolgus Macaques
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents, Wares, and Antibodies
2.2. Animals
2.3. Vaccination and Sampling
2.4. ELISA for HA-Specific Antibodies
2.5. Blood Testing
2.6. Cytokine Testing
2.7. Isolation of WBCs
2.8. Isolation of RNAs
2.9. Quantitative Reverse Transcription PCR for Gene Expression Analyses
2.10. DNA Microarray for High-Throughput Gene Expression Analyses
2.11. Bioinformatic for Microarray Data Analyses
2.12. Data Expression and Statistical Analysis
3. Results
3.1. Complete Blood Count, Biochemical Blood Test, and Plasma CRP
3.2. HA-Specific Antibodies
3.3. Production of Inflammation-Associating Cytokines
3.4. Gene Expression of Immuno-Proinflammatory Factors
3.5. Microarray Analyses and Bioinformatics
3.5.1. Upregulated Genes
3.5.2. Downregulated Genes
4. Discussion
4.1. Poly(I:C) Adjuvant
4.2. Sublingual Poly(I:C)-Adjuvanted Vaccination
4.3. Genes Upregulated by Sublingual Vaccine with HA Antigen and Poly(I:C) Adjuvant
4.4. Genes Downregulated by Sublingual Vaccine with HA Antigen and Poly(I:C) Adjuvant
4.5. A Balance State of Immune-Enhancing and -Suppressive Response Induced by the Sublingual Vaccine
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gene Symbol | Fold Change | Product. Description. Function [Reference]. | Expected Effect * |
---|---|---|---|
CLEC4G | 2.2 | C-type lectin. Receptor of PAMP [16]. Activation of inflammatory reactions [17]. Transcript variants [18]. | ↑ |
PF4V1 | 2.2 | Also known as CXCL4L1. Chemoattractant of T and NK cells [19]. | ↑ |
KLF1 | 2.1 | Zn-finger transcription factor. Transcription of γ-globin gene. Upregulation of CD274 in Tregs [20]. | ↓ |
OLFM1 | 2.1 | Nervous system. Inhibition of non-canonical NF-κB pathway in CRC [21]. | ↓ |
GNG11 | 2.0 | G protein gamma family. Downregulated in splenic marginal zone lymphomas [22]. | ↓ |
Gene Symbol | Fold Change | Product. Description. Function [Reference]. | Expected Effect * |
---|---|---|---|
NEURL1B | 0.45 | Ubiquitin protein ligase. Development of the nervous system [23]. Downregulated in CRC tissues [24]. Downregulated by Poly(I:C) adjuvant [8]. | ↑ |
CHST15 | 0.45 | Sulfotransferase. Expressed in B-cell lineage. Upregulation of RAG1 [25]. | ↓ |
MOB3A | 0.48 | Protein kinase activator. Inhibition of GC through the Hippo pathway [26]. | ↑ |
ANXA6 | 0.48 | Expressed in T cells. Component of T-cell plasma membrane. Stimulation of helper T cells [27]. | ↓ |
DNAJA3 | 0.48 | Mitochondrial HSP. Stimulation of ATPase activity of Hsp70. Activation of NF-κB [28]. | ↓ |
HSPH1 | 0.49 | HSP. Replacement of Hsp70-bound ADP with ATP. Holdase and disaggregase activity [29]. Stimulation of NF-κB signaling in activated B-cell diffuse large B-cell lymphoma [30]. | ↓ |
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Yamamoto, T.; Hirano, M.; Mitsunaga, F.; Wasaki, K.; Kotani, A.; Tajima, K.; Nakamura, S. Molecular Events in Immune Responses to Sublingual Influenza Vaccine with Hemagglutinin Antigen and Poly(I:C) Adjuvant in Nonhuman Primates, Cynomolgus Macaques. Vaccines 2024, 12, 643. https://doi.org/10.3390/vaccines12060643
Yamamoto T, Hirano M, Mitsunaga F, Wasaki K, Kotani A, Tajima K, Nakamura S. Molecular Events in Immune Responses to Sublingual Influenza Vaccine with Hemagglutinin Antigen and Poly(I:C) Adjuvant in Nonhuman Primates, Cynomolgus Macaques. Vaccines. 2024; 12(6):643. https://doi.org/10.3390/vaccines12060643
Chicago/Turabian StyleYamamoto, Tetsuro, Makoto Hirano, Fusako Mitsunaga, Kunihiko Wasaki, Atsushi Kotani, Kazuki Tajima, and Shin Nakamura. 2024. "Molecular Events in Immune Responses to Sublingual Influenza Vaccine with Hemagglutinin Antigen and Poly(I:C) Adjuvant in Nonhuman Primates, Cynomolgus Macaques" Vaccines 12, no. 6: 643. https://doi.org/10.3390/vaccines12060643
APA StyleYamamoto, T., Hirano, M., Mitsunaga, F., Wasaki, K., Kotani, A., Tajima, K., & Nakamura, S. (2024). Molecular Events in Immune Responses to Sublingual Influenza Vaccine with Hemagglutinin Antigen and Poly(I:C) Adjuvant in Nonhuman Primates, Cynomolgus Macaques. Vaccines, 12(6), 643. https://doi.org/10.3390/vaccines12060643