Extending the Breadth of Influenza Vaccines: Status and Prospects for a Universal Vaccine

Fox, Annette; Quinn, Kylie M.; Subbarao, Kanta

doi:10.1007/s40265-018-0958-7

Cited by 13 publications

(10 citation statements)

References 165 publications

(168 reference statements)

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“…We were able to delineate the dynamics of BIRFLU infection by bioluminescence imaging and detected a luminescent signal as early as 2 days p.i. As previously described, a low sporadic background was also observed at the NLuc substrate injection site (26,32,46,48,50). By using real-time bioluminescent imaging, we visualized temporal changes in virus replication and tissue distribution in the same animals over time.…”

Section: Birflu Reporter Gene Expression Levels Correlate With Dose-dmentioning

confidence: 70%

“…BIRFLU fluorescence and bioluminescence kinetics correlation in mouse lungs. Although the in vivo dynamics of IAV infection have been previously studied using replication-competent viruses harboring reporter genes (26,29,32,(34)(35)(36)48), researchers were limited to the use of only one reporter (fluorescent or bioluminescent) as a surrogate marker of viral infection. Given the different physical and chemical properties of these two systems, some concerns exist about the interpretation and comparison of the data obtained using these approaches.…”

Section: Birflu Reporter Gene Expression Levels Correlate With Dose-dmentioning

confidence: 99%

“…Existing strategies to combat IAV include the use of vaccines and antivirals (3,15,(19)(20)(21)(22)(23). However, currently available vaccines and antivirals have moderate efficacy (3,(24)(25)(26)(27). Therefore, new strategies to combat IAV infections urgently need to be developed and implemented.…”

mentioning

confidence: 99%

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A Novel Fluorescent and Bioluminescent Bireporter Influenza A Virus To Evaluate Viral Infections

Nogales

Ávila‐Pérez

Rangel-Moreno

et al. 2019

J Virol

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Studying influenza A virus (IAV) requires the use of secondary approaches to detect the presence of virus in infected cells. To overcome this problem, we and others have generated recombinant IAV expressing fluorescent or luciferase reporter genes. These foreign reporter genes can be used as valid surrogates to track the presence of virus. However, the limited capacity for incorporating foreign sequences in the viral genome forced researchers to select a fluorescent or a luciferase reporter gene, depending on the type of study. To circumvent this limitation, we engineered a novel recombinant replication-competent bireporter IAV (BIRFLU) expressing both fluorescent and luciferase reporter genes. In cultured cells, BIRFLU displayed growth kinetics comparable to those of wild-type (WT) virus and was used to screen neutralizing antibodies or compounds with antiviral activity. The expression of two reporter genes allows monitoring of viral inhibition by fluorescence or bioluminescence, overcoming the limitations associated with the use of one reporter gene as a readout. In vivo, BIRFLU effectively infected mice, and both reporter genes were detected using in vivo imaging systems (IVIS). The ability to generate recombinant IAV harboring multiple foreign genes opens unique possibilities for studying virus-host interactions and for using IAV in high-throughput screenings (HTS) to identify novel antivirals that can be incorporated into the therapeutic armamentarium to control IAV infections. Moreover, the ability to genetically manipulate the viral genome to express two foreign genes offers the possibility of developing novel influenza vaccines and the feasibility for using recombinant IAV as vaccine vectors to treat other pathogen infections. IMPORTANCE Influenza A virus (IAV) causes a human respiratory disease that is associated with significant health and economic consequences. In recent years, the use of replication-competent IAV expressing an easily traceable fluorescent or luciferase reporter protein has significantly contributed to progress in influenza research. However, researchers have been forced to select a fluorescent or a luciferase reporter gene due to the restricted capacity of the influenza viral genome for including foreign sequences. To overcome this limitation, we generated, for the first time, a recombinant replication-competent bireporter IAV (BIRFLU) that stably expresses two reporter genes (one fluorescent and one luciferase) to track IAV infections in vitro and in vivo. The combination of cutting-edge techniques from molecular biology, animal research, and imaging technologies brings researchers the unique opportunity to use this new generation of reporter-expressing IAV to study viral infection dynamics in both cultured cells and animal models of viral infection. RESULTSGeneration of a BIRFLU expressing NLuc and Venus. To generate replicationcompetent bireporter IAV (BIRFLU) (Fig. 1), the sequence of NLuc and the porcine teschovirus 1 (PTV-1) 2A autoproteolytic cleavage site were cloned in front ...

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Section: Birflu Reporter Gene Expression Levels Correlate With Dose-dmentioning

confidence: 70%

Section: Birflu Reporter Gene Expression Levels Correlate With Dose-dmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Fluorescent and Bioluminescent Bireporter Influenza A Virus To Evaluate Viral Infections

Nogales

Ávila‐Pérez

Rangel-Moreno

et al. 2019

J Virol

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“…5,6 Also, the MF59 adjuvanted subunit influenza vaccine (Fluad) provides an improved immune response for those aged 65 years and older. 7 In addition, nanoemulsion adjuvant such as MF59 and AS03 have been proven to enhance the adaptive response by activating the innate immune system locally and increasing antigen uptake and presentation in draining lymph nodes. [8][9][10] However, Pandemrix which contains AS03 has been associated with an increased risk of narcolepsy in adolescent recipients in the 2009 H1N1 pandemic.…”

Section: Introductionmentioning

confidence: 99%

<p>O/W Nanoemulsion as an Adjuvant for an Inactivated H3N2 Influenza Vaccine: Based on Particle Properties and Mode of Carrying</p>

Zhao¹,

Zhu²,

Ying-bo³

2020

IJN

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Background and Purpose: Adjuvant can reduce vaccine dosage and acquire better immune protection to the body, which helps to deal with the frequent outbreaks of influenza. Nanoemulsion adjuvants have been proved efficient, but the relationship between their key properties and the controlled release which greatly affects immune response is still unclear. The present work explores the role of factors such as particle size, the polydispersity index (PDI), stability and the safety of nanoemulsions by optimizing the water concentration, oil phase and modes of carrying, to explain the impact of those key factors above on adjuvant effect. Methods: Isopropyl myristate (IPM), white oil, soybean oil, and grape-kernel oil were chosen as the oil phase to explore their roles in emulsion characteristics and the adjuvant effect. ICR mice were immunized with an emulsion-inactivated H3N2 split influenza vaccine mixture, to compare the nanoemulsion's adjuvant with traditional aluminium hydroxide or complete Freund's adjuvant. Results: Particle size of all the nanoemulsion formed in our experiment ranged from 20 nm to 200 nm and did not change much when diluted with water, while the PDI decreased obviously, indicating that the particles tended to become more dispersive. Formulas with 80% or 85.6% water concentration showed significant higher HAI titer than aluminium hydroxide or complete Freund's adjuvant, and adsorption rather than capsule mode showed higher antigen delivery efficiency. As mentioned about oil phase, G (IPM), F (white oil), H (soybean oil), and I (grape-kernel oil) showed a decreasing trend in their adjuvant efficiency, and nanoemulsion G was the best adjuvant with smaller and uniform particle size. Conclusion: Emulsions with a smaller, uniform particle size had a better adjuvant effect, and the adsorption mode was generally more efficient than the capsule mode. The potential adjuvant order of the different oils was as follows: IPM > white oil > soybean oil > grape-kernel oil.

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“…Bioinformatic tools are being used to identify epitopes which can be developed into vaccines for influenza A [ 38 , 39 ]. Epitopes for M2 and NP proteins been identified as vaccine candidates and are being developed [ 37 , 40 ].…”

Section: Introductionmentioning

confidence: 99%

Insights from the comparison of genomic variants from two influenza B viruses grown in the presence of human antibodies in cell culture

et al. 2020

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Understanding the extent and limitation of viral genome evolution can provide insight about potential drug and vaccine targets. Influenza B Viruses (IBVs) infect humans in a seasonal manner and causes significant morbidity and mortality. IBVs are negative-sense single-stranded RNA viruses with a segmented genome and can be divided into two antigenically distinct lineages. The two lineages have been circulating and further evolving for almost four decades. The immune response to IBV infection can lead to antibodies that target the strain causing the infection. Some antibodies are cross-reactive and are able to bind strains from both lineages but, because of antigenic drift and immunodominance, both lineages continue to evolve and challenge human health. Here we investigate changes in the genomes of an IBVs from each lineage after passage in tissue culture in the presence of human sera containing polyclonal antibodies directed toward antigenically and temporally distinct viruses. Our previous analysis of the fourth segment, which encodes the major surface protein HA, revealed a pattern of change in which signature sequences from one lineage mutated to the signature sequences of the other lineage. Here we analyze genes from the other genomic segments and observe that most of the quasispecies’ heterogeneity occurs at the same loci in each lineage. The nature of the variants at these loci are investigated and possible reasons for this pattern are discussed. This work expands our understanding of the extent and limitations of genomic change in IBV.

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Extending the Breadth of Influenza Vaccines: Status and Prospects for a Universal Vaccine

Cited by 13 publications

References 165 publications

A Novel Fluorescent and Bioluminescent Bireporter Influenza A Virus To Evaluate Viral Infections

A Novel Fluorescent and Bioluminescent Bireporter Influenza A Virus To Evaluate Viral Infections

<p>O/W Nanoemulsion as an Adjuvant for an Inactivated H3N2 Influenza Vaccine: Based on Particle Properties and Mode of Carrying</p>

Insights from the comparison of genomic variants from two influenza B viruses grown in the presence of human antibodies in cell culture

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