PreprintArticleVersion 1This version is not peer-reviewed
Safety Assessment of a Sublingual Vaccine Formulated with Poly(I:C) Adjuvant and Influenza HA Antigen in Mice and Macaque Monkeys: Comparison with Intranasal Vaccine
Version 1
: Received: 27 September 2024 / Approved: 29 September 2024 / Online: 30 September 2024 (02:41:11 CEST)
How to cite:
Yamamoto, T.; Mitsunaga, F.; Wasaki, K.; Kotani, A.; Tajima, K.; Nakamura, S. Safety Assessment of a Sublingual Vaccine Formulated with Poly(I:C) Adjuvant and Influenza HA Antigen in Mice and Macaque Monkeys: Comparison with Intranasal Vaccine. Preprints2024, 2024092327. https://doi.org/10.20944/preprints202409.2327.v1
Yamamoto, T.; Mitsunaga, F.; Wasaki, K.; Kotani, A.; Tajima, K.; Nakamura, S. Safety Assessment of a Sublingual Vaccine Formulated with Poly(I:C) Adjuvant and Influenza HA Antigen in Mice and Macaque Monkeys: Comparison with Intranasal Vaccine. Preprints 2024, 2024092327. https://doi.org/10.20944/preprints202409.2327.v1
Yamamoto, T.; Mitsunaga, F.; Wasaki, K.; Kotani, A.; Tajima, K.; Nakamura, S. Safety Assessment of a Sublingual Vaccine Formulated with Poly(I:C) Adjuvant and Influenza HA Antigen in Mice and Macaque Monkeys: Comparison with Intranasal Vaccine. Preprints2024, 2024092327. https://doi.org/10.20944/preprints202409.2327.v1
APA Style
Yamamoto, T., Mitsunaga, F., Wasaki, K., Kotani, A., Tajima, K., & Nakamura, S. (2024). Safety Assessment of a Sublingual Vaccine Formulated with Poly(I:C) Adjuvant and Influenza HA Antigen in Mice and Macaque Monkeys: Comparison with Intranasal Vaccine. Preprints. https://doi.org/10.20944/preprints202409.2327.v1
Chicago/Turabian Style
Yamamoto, T., Kazuki Tajima and Shin Nakamura. 2024 "Safety Assessment of a Sublingual Vaccine Formulated with Poly(I:C) Adjuvant and Influenza HA Antigen in Mice and Macaque Monkeys: Comparison with Intranasal Vaccine" Preprints. https://doi.org/10.20944/preprints202409.2327.v1
Abstract
A sublingual vaccine comprising Poly(I:C) adjuvant and influenza HA antigen was evaluated for safety in both mice and macaque monkeys relative to its intranasal counterpart. Safety was assessed with harmful effects corresponding to upregulation of the inflammation-associated genes: Saa3, Tnf, IL6, IL1b, Ccl2, Timp1, C2, Ifi4, Aif1, Omp, Nos2, and/or Gzmb in mice and SAA2, TNF, IL6, IL1B, CCL2, TIMP, C2, AIF1, and GZMB in macaques. Quantitative gene expression analyses were performed using RT-qPCR with RNA samples from four tissues: olfactory bulb, pons, lung, tongue, and (submandibular) lymph node from both mice and macaques. In mice, the intranasally delivered vaccine markedly upregulated the inflammation-related genes in the olfactory bulb 1 day and 7 days after vaccination. The adverse effects of intranasal vaccination were also observed in macaques, however to a lesser extent than in mice. The intranasal vaccination also upregulated these genes in the pons of both mice and macaques. In contrast, the sublingual vaccine did not adversely affect the olfactory bulb or pons in either mice or macaques. The intranasally administered vaccine significantly upregulated these genes in the lungs only 1 day after vaccination, but not 7 days later, in both mice and macaques. We conclude that intranasal vaccination results in unfavorable side effects corresponding to upregulated inflammatory genes in the brain (olfactory bulb and pons). Sublingual vaccination, however, did not induce these side effects in either mice or macaque and was hence evaluated as safe.
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
