Nucleoprotein as a Promising Antigen for Broadly Protective Influenza Vaccines

Rak, Alexandra; Isakova-Sivak, Irina; Rudenko, Larisa

doi:10.3390/vaccines11121747

Cited by 11 publications

(3 citation statements)

References 159 publications

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“…Such information shall be helpful in developing antiviral agents that target these structured relationships and, therefore, provide broad-spectrum efficacy agents that are also adaptable across multiple variants and subtypes and could be targeted by vaccines to elicit a robust immune response. Since these mutations enhance the virus's stability and potential immunogenicity, vaccines that can induce strong and broad immune responses against these conserved regions might offer cross-protection against multiple variants [14] . The particular mutations found in the Delta variant, like D63G, R203M, D377Y, and G215C, are significant.…”

Section: Discussionmentioning

confidence: 99%

Genomic Insights into SARS-CoV-2 Evolution: Nucleocapsid Gene Mutations in West Sumatra, Indonesia

Linosef,

Hasmiwati,

Jamsari

2024

Int J Res Rev

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The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has necessitated a comprehensive understanding of viral mutations, particularly in the nucleocapsid protein, which plays a crucial role in the virus's life cycle and interaction with the host immune system. This study aims to analyze the nucleocapsid (N) gene mutations in SARS-CoV-2 variants isolated from West Sumatra during the pandemic. A dataset of 352 SARS-CoV-2 sequences from local COVID-19 cases was examined to identify N gene mutations and assess their prevalence across different variants. The primary mutations identified were R203K and G204R in the ancestral and Omicron variants. However, the D63G and D377Y mutation is present in the Delta variant. These mutations are implicated in enhancing viral infectivity and potential immune evasion. Notably, the Omicron variant showed additional deletions and mutations (P13L, E31-, R32-, S33-, and S413R) that harm protein expansion for structural stability and functionality of the nucleocapsid protein. The conservation of specific mutations across variants suggests their fundamental role in viral replication and immune interaction. Variant-specific mutations may represent adaptive responses to immune pressure or other environmental factors, with significant implications for viral transmissibility and pathogenicity. Understanding the impact of nucleocapsid protein mutations provides critical insights into the evolutionary dynamics of SARS-CoV-2 and aids in developing effective vaccines and therapeutics. Continued surveillance and detailed functional studies are essential to manage the pandemic and prepare for future viral outbreaks. Keywords: SARS-CoV-2, nucleocapsid protein, N gene, mutations, viral evolution.

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Section: Discussionmentioning

confidence: 99%

Genomic Insights into SARS-CoV-2 Evolution: Nucleocapsid Gene Mutations in West Sumatra, Indonesia

Linosef,

Hasmiwati,

Jamsari

2024

Int J Res Rev

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“…NP is crucial for the packaging and replication of viral RNA, aiding in the transcription of the viral genetic material. M2 acts as a proton-selective ion channel that is critical for viral entry. , To date, effective drugs for acute respiratory infections remain limited. A previous study highlighted the role of excessive lung inflammation, known as the “cytokine storm”, as a major contributor to the critical illness and mortality associated with respiratory infections .…”

Section: Introductionmentioning

confidence: 99%

Feruloylated Oligosaccharides Prevented Influenza-Induced Lung Inflammation via the RIG-I/MAVS/TRAF3 Pathway

Deng,

Wei,

Wang

et al. 2024

J. Agric. Food Chem.

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Uncontrolled inflammation contributes significantly to the mortality in acute respiratory infections. Our previous research has demonstrated that maize bran feruloylated oligosaccharides (FOs) possess notable anti-inflammatory properties linked to the NF-kB pathway regulation. In this study, we clarified that the oral administration of FOs moderately inhibited H1N1 virus infection and reduced lung inflammation in influenza-infected mice by decreasing a wide spectrum of cytokines (IFN-α, IFN-β, IL-6, IL-10, and IL-23) in the lungs. The mechanism involves FOs suppressing the transduction of the RIG-I/MAVS/TRAF3 signaling pathway, subsequently lowering the expression of NF-κB. In silico analysis suggests that FOs have a greater binding affinity for the RIG-I/MAVS signaling complex. This indicates that FOs have potential as promising targets for immune modulation. Moreover, in MAVS knockout mice, we confirmed that the anti-inflammatory function of FOs against influenza depends on MAVS. Comprehensive analysis using 16S rRNA gene sequencing and metabolite profiling techniques showed that FOs have the potential to restore immunity by modulating the gut microbiota. In conclusion, our study demonstrates that FOs are effective antiinflammatory phytochemicals in inhibiting lung inflammation caused by influenza. This suggests that FOs could serve as a potential nutritional strategy for preventing the H1N1 virus infection and associated lung inflammation.

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“…Thus, here lies the opportunity for vaccines that target conserved internal proteins to induce a durable broadly reactive T-cell response. These could either be live attenuated influenza vaccines [11,12], which are directly applicable, or novel, so-called universal influenza vaccines that specifically target internal proteins and may be more potent [13,14].…”

Section: Introductionmentioning

confidence: 99%

The Memory-CD8+-T-Cell Response to Conserved Influenza Virus Epitopes in Mice Is Not Influenced by Time Since Previous Infection

Lanfermeijer,

van de Ven,

Hendriks

et al. 2024

Vaccines

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To protect older adults against influenza A virus (IAV) infection, innovative strategies are imperative to overcome the decrease in protective immune response with age. One approach involves the boosting of CD8+ T cells at middle age that were previously induced by natural infection. At this stage, the immune system is still fit. Given the high conservation of T-cell epitopes within internal viral proteins, such a response may confer lasting protection against evolving influenza strains at older age, also reducing the high number of influenza immunizations currently required. However, at the time of vaccination, some individuals may have been more recently exposed to IAV than others, which could affect the T-cell response. We therefore investigated the fundamental principle of how the interval between the last infection and booster immunization during middle age influences the CD8+ T-cell response. To model this, female mice were infected at either 6 or 9 months of age and subsequently received a heterosubtypic infection booster at middle age (12 months). Before the booster infection, 6-month-primed mice displayed lower IAV-specific CD8+ T-cell responses in the spleen and lung than 9-month-primed mice. Both groups were better protected against the subsequent heterosubtypic booster infection compared to naïve mice. Notably, despite the different CD8+ T-cell levels between the 6-month- and 9-month-primed mice, we observed comparable responses after booster infection, based on IFNγ responses, and IAV-specific T-cell frequencies and repertoire diversity. Lung-derived CD8+ T cells of 6- and 9-month-primed mice expressed similar levels of tissue-resident memory-T-cell markers 30 days post booster infection. These data suggest that the IAV-specific CD8+ T-cell response after boosting is not influenced by the time post priming.

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Nucleoprotein as a Promising Antigen for Broadly Protective Influenza Vaccines

Cited by 11 publications

References 159 publications

Genomic Insights into SARS-CoV-2 Evolution: Nucleocapsid Gene Mutations in West Sumatra, Indonesia

Genomic Insights into SARS-CoV-2 Evolution: Nucleocapsid Gene Mutations in West Sumatra, Indonesia

Feruloylated Oligosaccharides Prevented Influenza-Induced Lung Inflammation via the RIG-I/MAVS/TRAF3 Pathway

The Memory-CD8+-T-Cell Response to Conserved Influenza Virus Epitopes in Mice Is Not Influenced by Time Since Previous Infection

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