Kitandwe Paul K, Rogers Paul, Hu Kai, Nayebare Owen, Blakney Anna K, McKay Paul F, Kaleebu Pontiano, Shattock Robin J
MRC/UVRI & LSHTM Uganda Research Unit, Plot 51-59 Nakiwogo Road, Entebbe P.O. Box 49, Uganda.
Department of Infectious Diseases, Imperial College London, Norfolk Place, London W2 1PG, UK.
Vaccines (Basel). 2024 Sep 24;12(10):1088. doi: 10.3390/vaccines12101088.
Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that causes high fetal and neonatal mortality rates in ruminants and sometimes severe to fatal complications like encephalitis and hemorrhagic fever in humans. There is no licensed RVF vaccine for human use while approved livestock vaccines have suboptimal safety or efficacy. We designed self-amplifying RNA (saRNA) RVF vaccines and assessed their humoral immunogenicity in mice. Plasmid DNA encoding the Rift Valley fever virus (RVFV) medium (M) segment consensus sequence (WT consensus) and its derivatives mutated to enhance cell membrane expression of the viral surface glycoproteins n (Gn) and c (Gc) were assessed for in vitro expression. The WT consensus and best-expressing derivative (furin-T2A) were cloned into a Venezuelan equine encephalitis virus (VEEV) plasmid DNA replicon and in vitro transcribed into saRNA. The saRNA was formulated in lipid nanoparticles and its humoral immunogenicity in BALB/c mice was assessed. High quantities of dose-dependent RVFV Gn IgG antibodies were detected in the serum of all mice immunized with either WT consensus or furin-T2A saRNA RVF vaccines. Significant RVFV pseudovirus-neutralizing activity was induced in mice immunized with 1 µg or 10 µg of the WT consensus saRNA vaccine. The WT consensus saRNA RVF vaccine warrants further development.
裂谷热（RVF）是一种由蚊子传播的病毒性人畜共患病，可导致反刍动物的胎儿和新生儿高死亡率，有时还会在人类中引发严重至致命的并发症，如脑炎和出血热。目前尚无获批用于人类的裂谷热疫苗，而已批准的家畜疫苗安全性或有效性欠佳。我们设计了自扩增RNA（saRNA）裂谷热疫苗，并在小鼠中评估了它们的体液免疫原性。对编码裂谷热病毒（RVFV）M（中）节段共有序列（野生型共有序列）及其经突变以增强病毒表面糖蛋白n（Gn）和c（Gc）细胞膜表达的衍生物的质粒DNA进行了体外表达评估。将野生型共有序列和表达最佳的衍生物（弗林蛋白酶-T2A）克隆到委内瑞拉马脑炎病毒（VEEV）质粒DNA复制子中，并在体外转录为saRNA。将saRNA制剂包裹在脂质纳米颗粒中，并评估其在BALB/c小鼠中的体液免疫原性。在用野生型共有序列或弗林蛋白酶-T2A saRNA裂谷热疫苗免疫的所有小鼠血清中均检测到大量剂量依赖性的RVFV Gn IgG抗体。在用1μg或10μg野生型共有序列saRNA疫苗免疫的小鼠中诱导出了显著的RVFV假病毒中和活性。野生型共有序列saRNA裂谷热疫苗值得进一步研发。
