The Development of a Novel Broad-Spectrum Influenza Polypeptide Vaccine Based on Multi-Epitope Tandem Sequences

Vaccines, Год журнала: 2025, Номер 13(1), С. 81 - 81

Опубликована: Янв. 17, 2025

Polypeptide vaccines have the potential to improve immune responses by targeting conserved and weakly immunogenic regions in antigens. This study aimed identify evaluate efficacy of a novel influenza universal vaccine candidate consisting multiple polypeptides derived from highly virus proteins hemagglutinin (HA), neuraminidase (NA), matrix protein 2 (M2). Immunoinformatics tools were used screen epitopes different subtypes (H1N1, H3N2, H5N1, H7N9, H9N2, IBV). A polypeptide vaccine, P125-H, was constructed linking using Ii-Key technology. The immunogenicity P125-H assessed mice MF59-adjuvanted via intraperitoneal injection. Hemagglutination inhibition (HI) neutralizing antibody measured, along with IFN-γ levels spleen lymphocytes. Protective evaluated viral challenge lethal doses H1N1 H7N9. Mice immunized generated high HI antibodies against strains. production significantly elevated lymphocytes upon stimulation vaccine. protected infection, reducing weight loss load lungs, mitigating lung pathology, decreasing mortality. induced broad cross-protection strains elicited robust responses. It demonstrates strong as for

Язык: Английский

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Development of broadly protective influenza B vaccines

npj Vaccines, Год журнала: 2025, Номер 10(1)

Опубликована: Янв. 7, 2025

Influenza B viruses pose a significant threat to global public health, leading severe respiratory infections in humans and, some cases, death. During the last 50 years, influenza of two antigenically distinct lineages (termed 'Victoria' and 'Yamagata') have circulated humans, necessitating different vaccine strains. In this study, we devised novel strategy involving reciprocal amino acid substitutions at sites where Victoria- Yamagata-lineage differ, generation 'hybrid' with potential protect against both lineages. Based on antigenic characterization, selected candidates assessed their protective efficacy ferret model. Notably, recombinant HA proteins conferred enhanced protection heterologous challenges compared respective wild-type antigens. These findings show our develop cross-lineage virus vaccines.

Язык: Английский

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Comprehensive analysis of lncRNAs and mRNAs revealed potential participants in the process of avian reovirus infection

Frontiers in Microbiology, Год журнала: 2025, Номер 16

Опубликована: Фев. 5, 2025

Avian reovirus (ARV), a double-stranded RNA virus, frequently induces immunosuppression in poultry, leading to symptoms such as irregular bleeding and spleen necrosis infected ducks. Since 2017, the morbidity mortality rates associated with ARV infection poultry have been on rise, progressively emerging significant viral disease impacting duck farming industry China. In our study, we collected embryo fibroblasts 18 h post-infection conducted transcriptome sequencing analysis. The analysis revealed that 3,818 mRNA expressions were up-regulated, 4,573 down-regulated, 472 long noncoding RNAs (LncRNAs) 345 lncRNAs down-regulated. We employed qRT-PCR validate results, confirming their accuracy. data indicated upregulation of PARP9 , TLR7 TRIM33 ATG5 genes, suggesting potential involvement infection. Notably, study identified novel functional lncRNA, MSTRG.9284.1 (It was named linc000889 present study), which inhibits replication at transcriptional, translational levels titer. Overall, this has numerous ARV-induced differentially expressed mRNAs lncRNAs, including lncRNA replication. This discovery provides new insights into mechanisms may contribute development prevention treatment strategies.

Язык: Английский

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A single dose of inactivated influenza virus vaccine expressing COBRA hemagglutinin elicits broadly-reactive and long-lasting protection

PLoS ONE, Год журнала: 2025, Номер 20(2), С. e0308680 - e0308680

Опубликована: Фев. 21, 2025

Influenza virus infections present a pervasive global health concern resulting in millions of hospitalizations and thousands fatalities annually. To address the influenza antigenic variation, computationally optimized broadly reactive antigen (COBRA) methodology was used to design hemagglutinin (HA) or neuraminidase (NA) for universal vaccine candidates. In this study, whole inactivated (WIV) split (SIV) formulations expressing either H1 COBRA HA H3 were formulated with without an adjuvant tested ferrets pre-existing anti-influenza immunity. A single dose COBRA-WIV elicited robust antibody response against H1N1 H3N2 viruses. contrast, COBRA-SIV antibodies that recognized fewer viruses, but R-DOATP, its specificity expanded. Vaccinated protected morbidity mortality following challenge A/California/07/2009 at 14 weeks post-vaccination reduced viral shedding post-infection compared naïve ferrets. However, COBRA-IIVs did not block transmission The contact infection induced less severe disease delayed than direct infection. Overall, WIV SIV plus R-DOTAP long-term protection pre-immune historical IMPORTANCE goal next-generation is provide various drifted strains. With previous studies evaluating HA-based vaccines, breadth activities confirmed two three vaccinations. commercial vaccine, only one shot required. administrated efficiently long-lasting pdm09 strain. Moreover, study showed different methods can lead severity, which emphasizes significance model selection. conducted evaluate by vaccination. This first longevity describing immune responses provides promising results potential clinical utilization.

Язык: Английский

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Live-attenuated pandemic H1N1 influenza vaccines expressing computationally optimized broadly reactive antigens (COBRAs) are immunogenic and protective in mice and ferrets

Vaccine, Год журнала: 2025, Номер 53, С. 127090 - 127090

Опубликована: Апрель 1, 2025

Язык: Английский

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Multivalent H3 COBRA-based influenza vaccine elicits enhanced immune response in a pre-immune elderly ferret model

Vaccine, Год журнала: 2025, Номер 56, С. 127156 - 127156

Опубликована: Апрель 22, 2025

Язык: Английский

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Deciphering immune responses: a comparative analysis of influenza vaccination platforms

Drug Discovery Today, Год журнала: 2024, Номер 29(9), С. 104125 - 104125

Опубликована: Авг. 2, 2024

Influenza still poses a significant challenge due to its high mutation rates and the low effectiveness of traditional vaccines. At present, antibodies that neutralize highly variable hemagglutinin antigen are major driver observed protection. To decipher how influenza vaccines can be improved, an analysis licensed vaccine platforms was conducted, contrasting strengths limitations their different mechanisms Through this review, it is evident these do not elicit robust cellular immune response critical for protecting high-risk groups. Emerging platforms, such as RNA vaccines, induce responses may additive recognized mechanism protection through inhibition overcome constraints provide broader, protective immunity. By combining both humoral responses, could help guide future development.

Язык: Английский

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A Single Dose of Inactivated Influenza Virus Vaccine Expressing COBRA Hemagglutinin Elicits Broadly-Reactive and Long-Lasting Protection

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 15, 2024

Abstract Influenza virus infections present a pervasive global health concern resulting in millions of hospitalizations and thousands fatalities annually. To address the influenza antigenic variation, computationally optimized broadly reactive antigen (COBRA) methodology was used to design hemagglutinin (HA) or neuraminidase (NA) for universal vaccine candidates. In this study, whole inactivated (WIV) split (SIV) formulations expressing either H1 COBRA HA H3 were formulated with without an adjuvant tested ferrets pre-existing anti-influenza immunity. A single dose COBRA-WIV elicited robust antibody response against H1N1 H3N2 viruses. contrast, COBRA-SIV antibodies that recognized fewer viruses, but R-DOATP, its specificity expanded. Vaccinated protected morbidity mortality following challenge A/California/07/2009 at 14 weeks post-vaccination reduced viral shedding post-infection compared naïve mock-vaccinated ferrets. However, COBRA-IIVs did not block transmission The contact infection induced less severe disease delayed than direct infection. Overall, WIV SIV plus R-DOTAP long-term protection pre-immune historical IMPORTANCE next-generation aims provide various drifted strains. HA-based vaccines elicit broadly-reactive two three vaccinations. people are administered vaccination current commercial vaccines. immunity shot long-lasting, pdmH1N1 challenge. This is first study describing immune responses by COBRA-IIV post-vaccination.

Язык: Английский

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Enhancing the use of T cells as a universal preventive measure against H3N2 influenza: Mechanism and implications

Health Science Reports, Год журнала: 2024, Номер 7(8)

Опубликована: Авг. 1, 2024

Язык: Английский

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