Aug 2026· Scientific Reports· Vol 16· 0 citations· 23 references
Medicine
TL;DR
Findings highlight the ability of IRO‑203 to induce measurable immune responses and to partially reduce viral RNA levels in a non-human primate challenge model and suggest that the nT-SeV vector represents an attractive platform for developing vaccines against other respiratory infectious diseases.
Abstract
This study indicates that IRO-203, a novel intranasal Coronavirus Disease 2019 vaccine based on a non-transmissible Sendai virus (nT-SeV) vector induces measurable humoral and cellular immune responses and shows signs of protective potential in a non-human primate challenge model. Immunogenicity was evaluated in both BALB/cA mice and African green monkeys (AGMs). Intranasal administration of IRO-203 led to the production of spike protein-specific IgG and IgA antibodies in serum and mucosal samples. Enzyme-Linked ImmunoSpot assays revealed increased IL-2 and IFN-γ secretion, indicating activation of cellular immunity. Neutralizing antibody titers were significantly boosted by repeated immunizations in both species. In the challenge study, AGMs vaccinated with IRO-203 and subsequently challenged via intranasal and intratracheal administration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibited statistically significant reductions in SARS-CoV-2 RNA levels in nasal and throat swabs at certain time points compared to controls, suggesting partial attenuation of viral replication. Although clinical symptoms were not assessed in this study, and further investigation is needed to determine the extent of protection conferred by IRO-203, these findings highlight the ability of IRO‑203 to induce measurable immune responses and to partially reduce viral RNA levels in a non‑human primate challenge model. Furthermore, they suggest that the nT-SeV vector represents an attractive platform for developing vaccines against other respiratory infectious diseases.
It is shown that a Wuhan-lineage-based multi-antigen VLP vaccine can provide cross-protection against an antigenically divergent SARS-CoV-2 variant that is not fully explained by detectable serum neutralizing activity alone, suggesting the importance of integrated immune responses involving humoral, cellular, and local immune mechanisms.
Seung-Ji Kim, Howon Kim, Seung-Eun Son et al.· Vaccine· 0 citations
A chimpanzee adenovirus (AdC68)-vectored vaccine expressing the Delta-XBB receptor-binding domain (RBD)-dimer is constructed and comprehensively compared the immune responses induced by intramuscular injection, intranasal administration, or aerosol inhalation, revealing that aerosol inhalation provided significantly better protection, without detectable replicating virus in the nasal tissue.
Xue-Yuan Liu, Yaling An, Huixin Duan et al.· mBio· 0 citations
Objective(s): Intranasal vaccination mimics natural infection and induces mucosal immunity against respiratory viruses. This study compared the immunogenicity and protective efficacy of a nucleoside-modified messenger RNA (mRNA) encoding the SARS-CoV-2 spike protein, encapsulated in lipid nanoparticles (LNPs), administered via intranasal (I.N) versus intramuscular (I.M) routes. Materials and Methods: BALB/c mice received mRNA-LNP vaccines at 1, 5, or 10 µg doses intramuscularly. Antibody responses (Immunoglobulin G/IgA [IgG/IgA]), neutralization titers (conventional virus neutralization test [cVNT]), and interferon-gamma (IFN-γ) responses were assessed to select the optimal dose. The selected 5 µg dose was then administered to mice and Syrian hamsters via I.N or I.M routes. Post-challenge, lung viral loads (50% Tissue Culture Infectious Dose [TCID50]/ml) and weight changes were evaluated. Results: The 5 µg dose induced robust humoral and cellular immunity (cVNT >5 log₂). Intranasal delivery elicited strong spike-specific IgA in nasal washes. Although I.M vaccination produced higher serum neutralizing titers (51.2 vs. 22.0), I.N vaccination conferred superior protection with a 4-log reduction in lung viral load (~10¹ TCID50/ml) versus I.M and controls (~10² TCID50/ml). I.N-vaccinated hamsters were completely protected from weight loss, whereas I.M-vaccinated animals showed mild weight reduction (~1%). Conclusion: Intranasal mRNA-LNP administration elicits potent mucosal and systemic immunity and provides superior protection against SARS-CoV-2 challenge compared to I.M vaccination, underscoring its promise as a transformative strategy for respiratory virus vaccines.
Mohsen Abdoli, H. Soleimanjahi, S. Soudi et al.· Iranian Journal of Basic Med...· 0 citations
Its ability to limit viral shedding from the upper respiratory tract and to mitigate SARS-CoV-2-induced pulmonary pathology, contributing to the preservation of lung vascular integrity, underscores the utility of mucosal immunization with Corfluvec as a valuable intranasal complement to current systemic vaccination strategies.
M. Stukova, A. Shurygina, Arman Muzhikyan et al.· Vaccines· 0 citations
Coronavirus disease 2019 (COVID-19) continues to cause outbreaks around the world despite the vast COVID-19 vaccination programs. Thus, it is important to continue developing better vaccines to protect vulnerable populations. Here, we studied the efficacy, safety, persistence and biodistribution of an adenovirus-based COVID-19 vaccine delivered intranasally. Our results confirmed that mucosal delivery leads to effective protection against infection in hamsters. A comparative study of different adenoviral vectors demonstrated that specifically Ad5-S-3M, expressing the SARS-CoV-2 spike glycoprotein ectodomain with inclusion of three common receptor binding domain mutations, induced a robust humoral immune response and effectively protected hamsters from SARS-CoV-2 infection. In addition, longitudinal analysis of vaccinated hamsters’ tissues demonstrated durable vaccine transgene expression and persistent vector DNA in the nasal turbinates. This persistence may be beneficial in increasing the duration of immunity. Expression of the S-3M did not cause any aberrant changes in the hamster tissues and resulted in very few changes in cellular mRNA expression in target tissues. Safety and biodistribution assessment demonstrated restricted non-target tissue distribution of intranasally delivered vector and no significant changes in clinical blood chemistry, underlining the safety of the vaccine. These results further support that intranasal delivery is a promising approach for mucosal vaccine administration against respiratory infection pathogens and extend our knowledge of Adeno-vector persistence.
N. Laham-Karam, P. Mäkinen, E. Koivulehto et al.· npj Vaccines· 0 citations
Intranasal boosting promotes greater variant-specific response at both the serum and cellular levels than i.m.n. boosting, and ongoing B cell repertoire and mAb analyses will provide mechanistic insight into how vaccination route reshapes clonal selection and maturation, informing rational vaccination design.
Xinyi Liu, Chieh-Yu Liang, Michael S. Diamond· Journal of Immunology· 0 citations
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