Aug 2026· Vaccines· Vol 14, pp. 684· 0 citations· 65 references
Medicine
TL;DR
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.
Abstract
Introduction: The development of bivalent mucosal vaccines capable of providing protection against both influenza and SARS-CoV-2 is a major public health focus. While most COVID-19 vaccines target the spike (S) protein, the highly conserved nucleocapsid (N) protein represents a strategic target for cross-reactive, cell-mediated immunity. This study evaluates Corfluvec, an intranasal vaccine candidate based on an attenuated NS1-truncated influenza vector expressing a fragment of the SARS-CoV-2 N protein. Methods: Protective efficacy, including viral load and pathomorphological changes in the lungs and vessels, was evaluated in Syrian hamsters challenged with high and low doses of SARS-CoV-2 (lineage B.1.1). Cross-protective efficacy against homologous and heterologous influenza A strains (H1N1pdm09, H3N2, and A/PR/8/1934) was tested in a lethal murine model. Additionally, immunogenicity of Corfluvec applied via human-compatible delivery device was tested in cynomolgus macaques (Macaca fascicularis). Results: In Syrian hamsters, vaccination significantly reduced viral loads in the lungs and nasal turbinates. Histopathological analysis revealed a preservation of lung vascular integrity: vaccinated animals showed stable CD31 expression and controlled Ki-67 proliferative activity, accompanied by a marked reduction in vasculitis and perivascular edema compared to placebo controls. In mice, the vaccine provided 100% protection against homologous and heterologous influenza virus challenges. In macaques, the two-dose intranasal immunization was well-tolerated and induced significant systemic IgG and mucosal sIgA responses, alongside robust N-specific IFNγ+ T-cell activation. Conclusions: Corfluvec is a promising bivalent vaccine candidate that provides dual protection against influenza and COVID-19. 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.
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
Over the past two decades, three major coronavirus (CoV) outbreaks–SARS, MERS, and COVID-19–have occurred, all caused by Beta-coronaviruses. Future outbreaks of yet-undiscovered CoVs with pandemic potential are anticipated. This underscores the urgent need for a broadly protective CoV vaccine. We hypothesize that targeting conserved regions of the CoV genome, such as the membrane (M) and nucleocapsid (N) proteins shared across Sarbecoviruses, can provide cross-protective immunity.
To induce mucosal immune responses at the site of CoV infection (upper respiratory tract), we used papillomavirus-like particles (VLPs) as a delivery vector. Vaccine constructs were designed using rearranged SARS-CoV-2 Omicron-XEC M and N sequences fused to ubiquitin to enhance antigen processing and T cell activation. These constructs were cloned into a pVax1 vector and expressed in HEK293T cells. Expression was confirmed by RT-PCR and Western blotting. The constructs were then packaged into pseudoviruses using bovine papillomavirus VLPs. Mice were immunized with these pseudoviruses.
Intracellular cytokine staining revealed antigen-specific T cell responses in lymph nodes and spleens of immunized mice following peptide stimulation. These responses were absent in control animals. Furthermore, vaccinated transgenic K18-hACE2 mice showed protection against heterologous challenge with SARS-CoV-2 Omicron-KP.3, indicating cross-variant efficacy.
Our findings demonstrate that mucosal delivery of conserved CoV antigens via papillomavirus VLPs induces strong, antigen-specific T cell responses and protects against heterologous SARS-CoV-2 challenge. This strategy shows promise for developing a pan-coronavirus vaccine.
NIH
Vaccines and Immunotherapy (VAC)
Aidan Dorn, Hansam Cho, Lanying Du et al.· Journal of Immunology· 0 citations
ABSTRACT The major route of COVID-19 vaccination currently is via intramuscular injection. Data from clinical trials and real-world studies have demonstrated its effectiveness in preventing severe illness and death caused by SARS-CoV-2 infection. However, its protective efficacy against SARS-CoV-2 infection and transmission in situ remains relatively low. Given that SARS-CoV-2, especially the Omicron variant and its sub-variants, primarily infects and replicates in the human upper respiratory tract, mucosal immune responses are crucial for preventing viral infection. Therefore, we constructed a chimpanzee adenovirus (AdC68)-vectored vaccine expressing the Delta-XBB receptor-binding domain (RBD)-dimer and comprehensively compared the immune responses induced by intramuscular injection, intranasal administration, or aerosol inhalation. Our results revealed that aerosol inhalation of the recombinant AdC68 vaccine induced robust systemic and mucosal immune responses and immune memory, particularly activating memory T cells in the lungs with a long duration in the mouse model. Additionally, we assessed long-term protection against a SARS-CoV-2 XBB.1 challenge after ~6 months following a booster vaccination with AdC68-Delta-XBB via different immunization routes. We found that, compared with the intramuscular route, aerosol inhalation provided significantly better protection, without detectable replicating virus in the nasal tissue. This study demonstrates that the AdC68-Delta-XBB vaccine induces robust mucosal immune responses via aerosol inhalation vaccination and prevents SARS-CoV-2 infection in mucosa. IMPORTANCE Immunity induced by first-generation COVID-19 vaccines administered by intramuscular injection is highly effective against severe disease and death but is limited in its ability to prevent viral infection and transmission. A more cost-effective and practical vaccine delivered by the respiratory route is needed to better understand mucosal immune responses and to assess protective efficacy. This study evaluated the immune responses and protective efficacy elicited by intramuscular injection, intranasal administration, or aerosol inhalation of AdC68-Delta-XBB in a mouse model and demonstrated that the aerosol inhalation approach is particularly advantageous for robustly stimulating both systemic and mucosal immune responses. These findings will help guide future clinical development and provide a basis for developing vaccines against other respiratory pathogens. Immunity induced by first-generation COVID-19 vaccines administered by intramuscular injection is highly effective against severe disease and death but is limited in its ability to prevent viral infection and transmission. A more cost-effective and practical vaccine delivered by the respiratory route is needed to better understand mucosal immune responses and to assess protective efficacy. This study evaluated the immune responses and protective efficacy elicited by intramuscular injection, intranasal administration, or aerosol inhalation of AdC68-Delta-XBB in a mouse model and demonstrated that the aerosol inhalation approach is particularly advantageous for robustly stimulating both systemic and mucosal immune responses. These findings will help guide future clinical development and provide a basis for developing vaccines against other respiratory pathogens.
Xueyuan Liu, Yaling An, Huixin Duan et al.· mBio· 0 citations
It is hypothesized that next-generation CoV vaccines incorporating highly conserved SARS-CoV-2 T cell antigens would confer potent, broad, long-lasting cross-protective immunity against multiple VOCs.
Swayam Prakash, N. Dhanushkodi, Afshana Quadiri et al.· npj Vaccines· 0 citations
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.
A multicomponent vaccine targeting seasonal influenza and coronavirus disease 2019 (COVID-19) may reduce disease burden by providing simultaneous protection in a single injection. We report findings from Part 1 (Japan) of a phase 3, Asia-Pacific, randomized, observer-blind study evaluating immunogenicity, reactogenicity, and safety of mRNA-based multicomponent vaccine mRNA-1083, combining influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens. Participants aged ≥50 years were randomized (1:1) to receive mRNA-1083 + placebo or Japan-licensed influenza hemagglutinin (HA) vaccine + mRNA-1273. Overall, 2022 participants were randomized, and 2013 received study intervention. At Day 29, mRNA-1083 elicited noninferior immune responses versus active comparators for all evaluated influenza strains and SARS-CoV-2. Among high-risk participants (aged ≥65 years and 60 to <65 years with ≥1 comorbidity), noninferiority of mRNA-1083 was demonstrated for comparator-matched influenza strains and SARS-CoV-2. In the overall study population, mRNA-1083 demonstrated superiority for the comparator-matched influenza strains and for SARS-CoV-2. At Day 181, immune responses remained above baseline and were comparable to or numerically higher than those elicited by active comparators. Most solicited adverse reactions were grade 1 or 2. There were no cases of myocarditis or pericarditis, and no reported serious adverse events or deaths related to study intervention. Overall, mRNA-1083 demonstrated an acceptable safety profile, eliciting noninferior and superior immune responses against influenza and SARS-CoV-2 in the high-risk and overall study population, respectively. Immune responses were maintained through 6 months post-vaccination. These findings support mRNA-1083 as a single-dose approach to seasonal vaccination against influenza and SARS-CoV-2 in adults ≥50 years. ClinicalTrials.govidentifier: NCT06694389 (https://clinicaltrials.gov/study/NCT06694389).
Lusine Kostanyan, Hiroyuki Fukase, Alexander Rumyantsev et al.· Vaccine· 0 citations