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Venezuelan equine encephalitis virus vaccine candidate (V3526) safety, immunogenicity and efficacy in horses

机译:委内瑞拉马脑炎病毒候选疫苗(V3526)在马中的安全性,免疫原性和功效

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摘要

A new vaccine, V3526, is a live-attenuated virus derived by site-directed mutagenesis from a virulent clone of the Venezuelan equine encephalitis virus (VEEV) IA/B Trinidad donkey (TrD) strain, intended for human use in protection against Venezuelan equine encephalitis (VEE). Two studies were conducted in horses to evaluate the safety, immunogenicity, ability to boost and protective efficacy of V3526 against challenges of TrD and VEEV IE 64A99. Horses were vaccinated subcutaneously (SC) with 10(7), 10(5), 10(3) or 10(2) plaque-forming units (pfu) of V3526. Control horses were sham immunized. In the first study, challenge viruses (TrD or 64A99) were administered SC 28 days post-vaccination (PV). No viremia and only mild fluctuation in white blood cell counts were observed PV. None of the V3526 vaccinated horses showed clinical signs of disease or pathology of VEE post-challenge (PC). In contrast, control horses challenged SC with 10(4)pfu TrD became viremic and showed classical signs of VEE beginning on Day 3 PC, including elevated body temperature, anorexia, leukopenia and malaise. Moderate to severe encephalitis was found in three of five control horses challenged with TrD. Control horses challenged with 64A99 failed to develop detectable viremia, but did exhibit a brief febrile episode at 1-3 days PC. None of the 10 immunized horses challenged with 64A99 became pyrexic. Twenty four of 25 horses immunized with V3526 in the first study developed serum neutralizing antibody to TrD and 64A99 within 14 days PV. Vaccinations with V3526, at doses as low as 10(2)pfu, were safe and efficacious in protecting horses against a virulent TrD virus challenge. The second study supported that repeat dosing resulted in an increase in serum neutralizing antibody to TrD.
机译:新型疫苗V3526是一种减毒活病毒,它是通过定点诱变衍生自委内瑞拉马脑炎病毒(VEEV)IA / B特立尼达驴(TrD)毒株的有力克隆,旨在用于保护人类免受委内瑞拉马脑炎(VEE)。在马匹中进行了两项研究,以评估V3526对TrD和VEEV IE 64A99攻击的安全性,免疫原性,增强能力和保护功效。用V3526的10(7),10(5),10(3)或10(2)噬菌斑形成单位(pfu)对马进行皮下接种(SC)。对照马假接种。在第一项研究中,接种疫苗(PV)后28天SC接种了挑战病毒(TrD或64A99)。无病毒血症,仅观察到白细胞计数轻度波动。接种V3526的马匹均未显示出攻击后VEE(PC)的疾病或病理的临床体征。相比之下,用10(4)pfu TrD攻击SC的对照马变成病毒血症,并在PC第3天开始显示VEE的经典体征,包括体温升高,厌食,白细胞减少和不适。在接受TrD攻击的5匹对照马中,有3匹发现了中度至重度脑炎。用64A99攻击的对照马未能发展出可检测的病毒血症,但在1-3天的PC上确实表现出短暂的发热。用64A99攻击的10匹免疫后的马都没有发热。在第一项研究中,用V3526免疫的25匹马中有24匹在PV的14天内开发了针对TrD和64A99的血清中和抗体。接种低至10(2)pfu的V3526疫苗可安全有效地保护马匹免受TrD病毒的强毒攻击。第二项研究支持重复给药导致TrD的血清中和抗体增加。

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