Nonviral delivery of self-amplifying RNA vaccines

Geall, Andrew J.; Verma, Ayush; Otten, Gillis R.; Shaw, Christine A.; Hekele, Armin; Banerjee, Kaustuv; Cu, Yen; Beard, Clayton W.; Brito, Luis A.; Krucker, Thomas; O’Hagan, Derek T.; Singh, Manmohan; Mason, Peter W.; Valiante, Nicholas M.; Dormitzer, Philip R.; Barnett, Susan W.; Rappuoli, Rino; Ulmer, Jeffrey B.; Mandl, Christian W.

doi:10.1073/pnas.1209367109

Cited by 552 publications

(567 citation statements)

References 38 publications

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“…Previously, we have shown that this imaging system could detect bioluminesce after the i.m. administration of a SAM vector encoding luciferase, and bioluminescence persisted for almost 2 mo after vaccination (10).…”

Section: Early In Vivo Ag Expression At Site Of Injectionmentioning

confidence: 99%

“…Ag-expressing (or reporter geneexpressing) replicons derived from the Venezuelan equine encephalitis virus genome containing the 39 untranslated region and packaging signal of Sindbis virus (SV) were electroporated into BHK cells along with defective helper RNAs encoding the SV capsid and glycoprotein genes (10). VRPs in the culture media were harvested and titrated.…”

Section: Vaccine Groupsmentioning

confidence: 99%

“…into quadriceps) on days 0 and 21: serum samples and spleens were collected 2 wk after the second immunization. Total IgG, IgG1, IgG2a titers, and T cell responses were determined as described previously (10). For T cell analysis, five spleens from identically vaccinated BALB/c mice were pooled, and single-cell suspensions were prepared.…”

Section: Rsv F Immunogenicity and Intracellular T Cell Analysismentioning

confidence: 99%

“…Encapsulation of RNA within LNPs was performed as previously described (10). In brief, the lipids 1,2-dilinoleyloxy-3-dimethylaminopropane (DLinDMA) (13) and 1,2-diastearoyl-sn-glycero-3-phosphocholine (DSPC; Genzyme), 1,2-dimyristoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (ammonium salt) (PEG-DMG 2000; Avanti Polar Lipids), and cholesterol (Sigma-Aldrich) were combined at a molar ratio of 40:10:2:48 molar percent (DLinDMA:DSPC: PEG-DMG 2000:cholesterol) by an ethanol dilution process to produce the LNPs.…”

Section: Lnp/rna Formulationmentioning

confidence: 99%

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Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine: Implications for Vaccine Design

Pepini

Pulichino

Carsillo

et al. 2017

The Journal of Immunology

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162

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RNA-based vaccines have recently emerged as a promising alternative to the use of DNA-based and viral vector vaccines, in part because of the potential to simplify how vaccines are made and facilitate a rapid response to newly emerging infections. SAM vaccines are based on engineered self-amplifying mRNA (SAM) replicons encoding an Ag, and formulated with a synthetic delivery system, and they induce broad-based immune responses in preclinical animal models. In our study, in vivo imaging shows that after the immunization, SAM Ag expression has an initial gradual increase. Gene expression profiling in injection-site tissues from mice immunized with SAM-based vaccine revealed an early and robust induction of type I IFN and IFN-stimulated responses at the site of injection, concurrent with the preliminary reduced SAM Ag expression. This SAM vaccine-induced type I IFN response has the potential to provide an adjuvant effect on vaccine potency, or, conversely, it might establish a temporary state that limits the initial SAM-encoded Ag expression. To determine the role of the early type I IFN response, SAM vaccines were evaluated in IFN receptor knockout mice. Our data indicate that minimizing the early type I IFN responses may be a useful strategy to increase primary SAM expression and the resulting vaccine potency. RNA sequence modification, delivery optimization, or concurrent use of appropriate compounds might be some of the strategies to finalize this aim.

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Section: Early In Vivo Ag Expression At Site Of Injectionmentioning

confidence: 99%

Section: Vaccine Groupsmentioning

confidence: 99%

Section: Rsv F Immunogenicity and Intracellular T Cell Analysismentioning

confidence: 99%

Section: Lnp/rna Formulationmentioning

confidence: 99%

See 2 more Smart Citations

Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine: Implications for Vaccine Design

Pepini

Pulichino

Carsillo

et al. 2017

The Journal of Immunology

Self Cite

162

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“…siRNA may also be used for therapeutic purpose like vaccine and chemical drugs. 9 Our present study is aimed to design a potential siRNA for inhibiting the translation of this ICP22 (US1) gene and hinder the overall replication process.…”

Section: Introductionmentioning

confidence: 99%

An in silico approach to design potential siRNA molecules for ICP22 (US1) gene silencing of different strains of human herpes simplex 1

Nur¹,

Amin²,

Alam³

et al. 2013

Journal of Young Pharmacists

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a b s t r a c tBackground: The herpes simplex virus (HSV-1) is a virus that manifests itself in viral infection with painful, watery blisters in the skin or on the genitals as well as mucous membrane such as the mouth or lips. During an outbreak, the disease is contagious particularly and is irredeemable with present technology. Genetic studies of HSV-1 have shown that ICP22 (US1) gene is an immediate early gene and is responsible for genome replication and also has contribution in viral infection. Method: For disease diagnosis, ICP22 (US1) gene may be suitable target. Viral activity can be controlled through RNA interference technology, a significant method for the post-transcriptional gene silencing. However, in different viral isolates there is a genetic variability; it is very challenging to design possible siRNA molecules which can silence the respective target genes. The work was done by using various computational tools as similarity search, target alignment, secondary structure prediction and RNA interaction evaluation. Result: In our study two effective siRNA molecules for ICP22 (US1) gene silencing of seven different strains of HSV-1 were rationally designed and authenticated using computational methods, which might lead to knockdown the viral activity. Conclusion: siRNA molecules were foreseen against ICP22 (US1) gene of different strains of HSV-1 as effective aspirant using computational methods. Thus, the approach may deliver a vision for the chemical synthesis of antiviral RNA molecule for treatment of HSV-1, at genomic level.

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Current Status of Cytomegalovirus Vaccines: 2016

Schleiss

2016

Encyclopedia of Life Sciences

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A vaccine against the debilitating effects of congenital cytomegalovirus (CMV) infection is a major public health priority. Vaccines against CMV may also improve the outcome of solid organ and haematopoietic stem‐cell transplantation. In spite of the long‐recognised morbidity caused by CMV infection, progress towards a licenced vaccine has been slow, owing to uncertainties about the key immunological correlates of protective immunity and the optimal vaccine expression approaches to employ. Driven by the encouraging (albeit suboptimal) benefit conferred by a recombinant CMV glycoprotein B (gB) vaccine against CMV infection and disease in recent clinical trials, there is currently increased interest in designing and evaluating a number of candidate vaccines in both preclinical models and controlled trials. Several new CMV vaccine candidates are currently undergoing evaluation in clinical trials. Major challenges must be met before a vaccine can be licenced. Chief among these challenges are: (1) the need to define the optimal constituents of CMV vaccines; (2) the need to define the metrics of protection that would be required for licensure of a vaccine for congenital CMV infection and (3) the necessity of solving the challenge of designing successful vaccines against reinfection. Key Concepts Congenital infection with CMV is the most common congenital viral infection and is responsible for a wide range of birth defects, including sensorineural hearing loss, mental retardation and developmental delay. Primary infection with CMV during pregnancy confers the greatest risk of foetal transmission, but recurrent infections are also common, and these infections can also lead to transmission of CMV with attendant disabilities. Immunity to CMV is complex, and involves both cellular and humoral immune responses. CMV encodes immune evasion genes that complicate the development of protective immunity, help promote reinfection and create challenges for vaccine design. A vaccine for congenital CMV is a major public health priority, but no licenced vaccines exist. Key targets of the humoral immune response to CMV and the cellular immune response include envelope glycoproteins, particularly gB and the PC proteins, and the pp65 and IE1 proteins, respectively. Several clinical trials of both live, attenuated CMV vaccines and subunit vaccines based on recombinant and/or vectored expression of specific immunogens have been conducted. Modest protection against CMV infection has been demonstrated by a recombinant, adjuvanted gB protein subunit vaccine, although the magnitude and duration of protection were suboptimal. Greater public awareness of congenital CMV is required to help drive efforts to develop and licence a protective vaccine.

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Nonviral delivery of self-amplifying RNA vaccines

Cited by 552 publications

References 38 publications

Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine: Implications for Vaccine Design

Induction of an IFN-Mediated Antiviral Response by a Self-Amplifying RNA Vaccine: Implications for Vaccine Design

An in silico approach to design potential siRNA molecules for ICP22 (US1) gene silencing of different strains of human herpes simplex 1

Current Status of Cytomegalovirus Vaccines: 2016

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