Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice.
Single dose of a replication-defective vaccinia virus expressing Zika virus-like particles is protective in mice.
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DOI：
10.1038/s41598-021-85951-7
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发表时间：
2021-03-22
影响因子：
4.6
通讯作者：
Verardi PH
中科院分区：
文献类型：
--
作者：
Jasperse B;O'Connell CM;Wang Y;Verardi PH
寨卡病毒（ZIKV）是一种主要由受感染的蚊子传播的黄病毒，可引起神经系统症状，如格林-巴利综合征和小头畸形。我们基于表达ZIKV前膜（prM）和包膜（E）蛋白的复制诱导型VACV（vIND）（vIND-ZIKV）开发了几种ZIKV的牛痘病毒（VACV）疫苗候选物。这些vIND-ZIKV含有四环素操纵子的元件，并且仅在四环素存在下复制。将候选疫苗库缩小到一种vIND-ZIKV，其在prM的信号肽中含有新突变，导致E的更高表达和分泌以及病毒样颗粒的产生，然后在小鼠中测试其安全性、免疫原性和功效。vIND-ZIKV在多西环素（DOX）的存在下在体外生长至高滴度，但在不存在DOX的情况下在体内是复制缺陷型的，在小鼠中不引起体重减轻。在不存在DOX（作为复制缺陷型病毒）的情况下用vIND-ZIKV接种一次的C57 BL/6小鼠产生了稳健水平的E肽特异性IFN-γ分泌脾细胞和抗E IgG滴度，以及适度水平的血清中和抗体。在单剂量的vIND-ZIKV后，用抗IFNARl抗体处理的接种小鼠完全免受攻击后的ZIKV病毒血症。此外，先前对VACV具有免疫力的小鼠产生了中等的抗E IgG滴度，其在加强疫苗接种后增加，并且仅在两次vIND-ZIKV疫苗接种后才被保护免于病毒血症。
Zika virus (ZIKV), a flavivirus transmitted primarily by infected mosquitos, can cause neurological symptoms such as Guillian–Barré syndrome and microcephaly. We developed several vaccinia virus (VACV) vaccine candidates for ZIKV based on replication-inducible VACVs (vINDs) expressing ZIKV pre-membrane (prM) and envelope (E) proteins (vIND-ZIKVs). These vIND-ZIKVs contain elements of the tetracycline operon and replicate only in the presence of tetracyclines. The pool of vaccine candidates was narrowed to one vIND-ZIKV containing a novel mutation in the signal peptide of prM that led to higher expression and secretion of E and production of virus-like particles, which was then tested for safety, immunogenicity, and efficacy in mice. vIND-ZIKV grows to high titers in vitro in the presence of doxycycline (DOX) but is replication-defective in vivo in the absence of DOX, causing no weight loss in mice. C57BL/6 mice vaccinated once with vIND-ZIKV in the absence of DOX (as a replication-defective virus) developed robust levels of E-peptide-specific IFN-γ-secreting splenocytes and anti-E IgG titers, with modest levels of serum-neutralizing antibodies. Vaccinated mice treated with anti-IFNAR1 antibody were completely protected from ZIKV viremia post-challenge after a single dose of vIND-ZIKV. Furthermore, mice with prior immunity to VACV developed moderate anti-E IgG titers that increased after booster vaccination, and were protected from viremia only after two vaccinations with vIND-ZIKV.
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影响因子：
5.4
作者：
Chang, GJJ;Hunt, AR;Davis, B
通讯作者：
Davis, B
DOI：
10.1016/j.omtm.2020.03.026
发表时间：
2020-06-12
影响因子：
4.7
作者：
Jasperse, Brittany;O'Connell, Caitlin M.;Verardi, Paulo H.
通讯作者：
Verardi, Paulo H.
影响因子：
11.1
作者：
Espinosa D;Mendy J;Manayani D;Vang L;Wang C;Richard T;Guenther B;Aruri J;Avanzini J;Garduno F;Farness P;Gurwith M;Smith J;Harris E;Alexander J
通讯作者：
Alexander J
影响因子：
5.5
作者：
Basu, Rupsa;Zhai, Lukai;Tumban, Ebenezer
通讯作者：
Tumban, Ebenezer
影响因子：
3.8
作者：
Boigard H;Alimova A;Martin GR;Katz A;Gottlieb P;Galarza JM
通讯作者：
Galarza JM