The Potential of Self-amplifying RNA Vaccines for Infectious Diseases and COVID-19

Lundström, Kenneth

doi:10.29252/vacres.7.1.25

Cited by 10 publications

(5 citation statements)

References 101 publications

(122 reference statements)

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“…One technology being applied in this development is the use of self-amplifying mRNA (sa-mRNA) that allows host cells to make copies of the vaccine mRNA, increasing the amount of protein produced with lower doses of administered mRNA. [11][12][13][14] Preclinical studies have shown sa-mRNA vaccines elicit a longer duration and broader activation of the immune response. 15 sa-mRNA COVID-19 vaccines were safe and immunogenic in human phase 1 studies -a dose-ranging primary vaccination study 16 and a small booster study in older adults.…”

Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine

Hồ,

Hughes,

Tạ

et al. 2023

Preprint

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Combination of waning immunity and lower effectiveness of approved COVID-19 vaccines against SARS-CoV-2 variants necessitates new vaccines. We evaluated the safety, immunogenicity and efficacy of a novel self-amplifying mRNA COVID-19 vaccine against the D614G variant, ARCT-154, in an integrated phase 1/2/3a/3b, randomized, observer-blind trial in Vietnamese adults. Two doses of ARCT-154 or placebo 28 days apart were well tolerated with mild to moderate transient adverse events. Four weeks after the second dose 94.1% (95% CI: 92.1–95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline titers of 14.5 (95% CI: 13.6–15.5). Most cases of confirmed COVID-19 eligible for efficacy analysis were due to the Delta variant. Absolute efficacy of ARCT-154 was 56.6% (95% CI: 48.7–63.3) against any COVID-19, and 95.3% (80.5–98.9) against severe COVID-19. We show ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease and COVID-associated death.

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Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine

Hồ,

Hughes,

Tạ

et al. 2023

Preprint

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show abstract

“…Preclinical and clinical applications of SAM viral vectors have proven to be efficient for vaccine development [13] . It has also been shown that recombinant SFV particles can be developed as prophylactic and therapeutic vaccine platforms against infectious diseases and various cancers since SFV-based antigen expression can induce humoral and cell-mediated immunity and have demonstrated protection against challenges with pathogens and tumor cells in animal models [14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

Packaging, Purification, and Titration of Replication-Deficient Semliki Forest Virus-Derived Particles as a Self-Amplifying mRNA Vaccine Vector

Savar

Vallet

Arashkia

et al. 2022

IBJ

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Background: Self-amplifying mRNA is the next-generation vaccine platform with the potential advantages in efficacy and speed of development against infectious diseases and cancer. The main aim was to present optimized and rapid methods for SFV-PD SAM preparation, its packaging, and titer determination. These protocols are provided for producing and harvesting the high yields of VRP-packaged SAM for vaccine studies. Methods: pSFV-PD-EGFP plasmid was linearized and subjected to in vitro transcription. Different concentrations of SFV-PD SAM were first transfected into HEK-293 and BHK-21 cell lines, and EGFP expression at different time points was evaluated by fluorescent microscopy. Replicon particle packaging was achieved by co-transfection of SFV-PD SAM and pSFV-Helper2 RNA into BHK-21 cells. The VRPs were concentrated using ultrafiltration with 100 kDa cut-off. The titers of replicon particles were determined by RT-qPCR. Results: In vitro transcribed SAM encoding EGFP was successfully transfected and expressed in HEK-293 and BHK-21 cell lines. Higher levels of EGFP expression was observed in BHK-21 compared to HEK-293 cells showing more stable protein overexpression and VRP packaging. Using ultrafiltration, the high yields of purified SFV-PD-EGFP particles were rapidly obtained with only minor loss of replicon particles. Accurate and rapid titer determination of replication-deficient particles was achieved by RT-qPCR. Conclusion: Using optimized methods for SAM transfection, VRP packaging, and concentration, high yields of SFV-PD VRPs could be produced and purified. The RT-qPCR demonstrated to be an accurate and rapid method for titer determination of replication deficient VRPs.

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“…The presence of RdRp leads to saRNA amplification in the cytoplasm 9 . Due to unique property of saRNA, high immune responses can be achieved with low doses 10 . Apart from the complex design of saRNA, its synthesis is no hard 8 .…”

Section: Introductionmentioning

confidence: 99%

The evaluation of novel oral vaccines based on self-amplifying RNA lipid nanparticles (saRNA LNPs), saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum to neutralize SARS-CoV-2 variants alpha and delta

Keikha

Hashemi-Shahri

Jebali

2021

Sci Rep

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The aim of this study was to present and evaluate novel oral vaccines, based on self-amplifying RNA lipid nanparticles (saRNA LNPs), saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum, to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) variants alpha and delta. After invitro evaluation of the oral vaccines on HEK293T/17 cells, we found that saRNA LNPs, saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum could express S-protein at both mRNA and protein levels. In the next step, BALB/c mice were orally vaccinated with saRNA LNPs, saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum at weeks 1 and 3. Importantly, a high titer of IgG and IgA was observed by all of them, sharply in week 6 (P < 0.05). In all study groups, their ratio of IgG2a/IgG1 was upper 1, indicating Th1-biased responses. Wild-type viral neutralization assay showed that the secreted antibodies in vaccinated mice and recovered COVID-19 patients could neutralize SARS-COV-2 variants alpha and delta. After oral administration of oral vaccines, biodistribution assay was done. It was found that all of them had the same biodistribution pattern. The highest concentration of S-protein was seen in the small intestine, followed by the large intestine and liver.

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The Potential of Self-amplifying RNA Vaccines for Infectious Diseases and COVID-19

Cited by 10 publications

References 101 publications

Safety and immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine

Safety and immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine

Packaging, Purification, and Titration of Replication-Deficient Semliki Forest Virus-Derived Particles as a Self-Amplifying mRNA Vaccine Vector

The evaluation of novel oral vaccines based on self-amplifying RNA lipid nanparticles (saRNA LNPs), saRNA transfected Lactobacillus plantarum LNPs, and saRNA transfected Lactobacillus plantarum to neutralize SARS-CoV-2 variants alpha and delta

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