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Development of a potent Zika virus vaccine using self-amplifying messenger RNA.

ABSTRACT: Zika virus (ZIKV) is the cause of a pandemic associated with microcephaly in newborns and Guillain-Barre syndrome in adults. Currently, there are no available treatments or vaccines for ZIKV, and the development of a safe and effective vaccine is a high priority for many global health organizations. We describe the development of ZIKV vaccine candidates using the self-amplifying messenger RNA (SAM) platform technology delivered by cationic nanoemulsion (CNE) that allows bedside mixing and is particularly useful for rapid responses to pandemic outbreaks. Two immunizations of either of the two lead SAM (CNE) vaccine candidates elicited potent neutralizing antibody responses to ZIKV in mice and nonhuman primates. Both SAM (CNE) vaccines protected these animals from ZIKV challenge, with one candidate providing complete protection against ZIKV infection in nonhuman primates. The data provide a preclinical proof of concept that a SAM (CNE) vaccine candidate can rapidly elicit protective immunity against ZIKV.

SUBMITTER: Luisi K

PROVIDER: S-EPMC7413734 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Development of a potent Zika virus vaccine using self-amplifying messenger RNA.

Luisi Kate K Morabito Kaitlyn M KM Burgomaster Katherine E KE Sharma Mayuri M Kong Wing-Pui WP Foreman Bryant M BM Patel Sonal S Fisher Brian B Aleshnick Maya A MA Laliberte Jason J Wallace Madison M Ruckwardt Tracy J TJ Gordon David N DN Linton Christine C Ruggiero Nicole N Cohen Jessica L JL Johnson Russell R Aggarwal Kunal K Ko Sung-Youl SY Yang Eun Sung ES Pelc Rebecca S RS Dowd Kimberly A KA O'Hagan Derek D Ulmer Jeffrey J Mossman Sally S Sambor Anna A Lepine Edith E Mascola John R JR Pierson Theodore C TC Graham Barney S BS Yu Dong D

Science advances 20200807 32

Zika virus (ZIKV) is the cause of a pandemic associated with microcephaly in newborns and Guillain-Barre syndrome in adults. Currently, there are no available treatments or vaccines for ZIKV, and the development of a safe and effective vaccine is a high priority for many global health organizations. We describe the development of ZIKV vaccine candidates using the self-amplifying messenger RNA (SAM) platform technology delivered by cationic nanoemulsion (CNE) that allows bedside mixing and is par ...[more]

PMID: 32821824

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Project description:RNA-baffsed vaccines have recently emerged as a promising alternative to the use of DNA-based and viral vector vaccines, in part due to 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 antigen, formulated with a synthetic delivery system, and induce broad-based immune responses in preclinical animal models. BALB/c mice (three biological replicates per group) were injected bilaterally intramuscularly (i.m.) with 50 Î¼l per quadriceps of Phosphate Buffered Saline alone (Control group), Ribonucleic Acid Expressing Respiratory Syncytial Virus F Protein (RNA) (500 ng), lipid nanoparticle (LNP) alone, or LNPâformulated RNA (LNP_RNA). A single quadriceps from each mouse was homogenized using QIAzol reagent and the FastPrepâ24 instrument (MP Bio). Total RNA was purified using RNeasy columns according to the manufacturerâs instructions (Qiagen). RNA labeling, hybridization, and scanning were performed using methods, reagents, software, and hardware purchased from Agilent Technologies. Briefly, 100 ng RNA was retro transcribed, labeled using Cy3, and column purified Qiagen. The efficiency of Cy3 dye incorporation was assessed on a NanoDrop 1000 instrument. Reactions with specific activities >6 pmol dye/Î¼g cRNA were used for hybridization. cRNA (1.65 Î¼g) was hybridized onto a 4 X 44 Whole Mouse Genome Microarray (G4122F). After scanning, images were analyzed using Feature Extraction 10.7.3.1 software. Microarray data was analyzed using the R/Bioconductor Limma openâsource package. Briefly, each spot was background corrected and spot intensities between arrays normalized using the quantile method. The average normalized spot intensity from experimental replicates was determined and differentially expressed genes (compared to the PBS control group) calculated using a moderated tâstatistic (Empirical Bayes method) followed by BenjaminiâHochberg false discovery rate (FDR) correction. Genes with an FDR adjusted pâvalue â¤ 0.05 and a foldâchange greater than or less than 2 (log2 = 1) were considered significantly changed. Functional clustering was performed using the DAVID online database. Heat maps were generated using Spotfire 4.0.3 software.

Dataset Information

Development of a potent Zika virus vaccine using self-amplifying messenger RNA.

Publications

Development of a potent Zika virus vaccine using self-amplifying messenger RNA.

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