Powers John M, Haese Nicole N, Denton Michael, Ando Takeshi, Kreklywich Craig, Bonin Kiley, Streblow Cassilyn E, Kreklywich Nicholas, Smith Patricia, Broeckel Rebecca, DeFilippis Victor, Morrison Thomas E, Heise Mark T, Streblow Daniel N
Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, United States of America.
PLoS Negl Trop Dis. 2021 Apr 1;15(4):e0009308. doi: 10.1371/journal.pntd.0009308. eCollection 2021 Apr.
Mayaro virus (MAYV) is an alphavirus endemic to South and Central America associated with sporadic outbreaks in humans. MAYV infection causes severe joint and muscle pain that can persist for weeks to months. Currently, there are no approved vaccines or therapeutics to prevent MAYV infection or treat the debilitating musculoskeletal inflammatory disease. In the current study, a prophylactic MAYV vaccine expressing the complete viral structural polyprotein was developed based on a non-replicating human adenovirus V (AdV) platform. Vaccination with AdV-MAYV elicited potent neutralizing antibodies that protected WT mice against MAYV challenge by preventing viremia, reducing viral dissemination to tissues and mitigating viral disease. The vaccine also prevented viral-mediated demise in IFN⍺R1-/- mice. Passive transfer of immune serum from vaccinated animals similarly prevented infection and disease in WT mice as well as virus-induced demise of IFN⍺R1-/- mice, indicating that antiviral antibodies are protective. Immunization with AdV-MAYV also generated cross-neutralizing antibodies against two related arthritogenic alphaviruses-chikungunya and Una viruses. These cross-neutralizing antibodies were protective against lethal infection in IFN⍺R1-/- mice following challenge with these heterotypic alphaviruses. These results indicate AdV-MAYV elicits protective immune responses with substantial cross-reactivity and protective efficacy against other arthritogenic alphaviruses. Our findings also highlight the potential for development of a multi-virus targeting vaccine against alphaviruses with endemic and epidemic potential in the Americas.
马亚罗病毒（MAYV）是一种南美洲和中美洲特有的甲病毒，与人类散发性疫情有关。MAYV感染会导致严重的关节和肌肉疼痛，可持续数周甚至数月。目前，尚无获批的疫苗或疗法来预防MAYV感染或治疗这种使人虚弱的肌肉骨骼炎症性疾病。在本研究中，基于非复制型人腺病毒V（AdV）平台开发了一种表达完整病毒结构多蛋白的预防性MAYV疫苗。用AdV-MAYV疫苗接种可诱导产生强效中和抗体，通过预防病毒血症、减少病毒向组织的传播以及减轻病毒疾病，保护野生型小鼠免受MAYV攻击。该疫苗还可预防IFN⍺R1-/-小鼠中病毒介导的死亡。来自接种疫苗动物的免疫血清的被动转移同样可预防野生型小鼠的感染和疾病，以及IFN⍺R1-/-小鼠的病毒诱导死亡，表明抗病毒抗体具有保护作用。用AdV-MAYV免疫还产生了针对两种相关的致关节炎甲病毒——基孔肯雅病毒和乌纳病毒的交叉中和抗体。这些交叉中和抗体在IFN⍺R1-/-小鼠受到这些异型甲病毒攻击后，对致死性感染具有保护作用。这些结果表明，AdV-MAYV可引发具有显著交叉反应性和对其他致关节炎甲病毒具有保护效力的保护性免疫反应。我们的研究结果还凸显了开发一种针对在美洲具有地方性和流行性潜力的甲病毒的多病毒靶向疫苗的可能性。
