Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity.

Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity.
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DOI:
10.1038/s41541-022-00532-7
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发表时间:
2022-09-23
期刊:
影响因子:
9.2
通讯作者:
--
中科院分区:
医学1区
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本研究的目的是进一步分析重组狂犬病毒载体SARS-CoV-2疫苗CORAVAX作为有效的COVID-19疫苗策略。CORAVAX已在动物模型中证明具有免疫原性和对SARS-CoV-2的保护作用。在这里,我们已经筛选了最高质量抗体滴度的佐剂,否定了预先存在的狂犬病媒介免疫的担忧,并确定了其作为长期COVID-19疫苗的潜力。我们已经在CORAVAX中测试了Toll样受体4(TLR 4)激动剂、炎性体激活剂和明矾佐剂,发现TLR 4激活的MPLA-AddaVax具有最大的潜力。我们跟踪了具有预先存在的狂犬病病毒免疫力的小鼠对CORAVAX的体液免疫应答,与未感染过狂犬病病毒的小鼠相比,没有观察到显著差异。然后,我们在免疫后几个月和1年内跟踪了对CORAVAX的免疫应答。小鼠保持高抗原特异性血清抗体滴度以及脾和骨髓中的长寿命抗体分泌细胞。我们相信这种狂犬病媒介策略可以解决其他COVID-19疫苗免疫力下降的问题。这些结果共同支持CORAVAX在持续的COVID-19大流行期间的潜力。
The objective of this study is to further analyze recombinant rabies virus-vectored SARS-CoV-2 vaccine, CORAVAX, as an effective COVID-19 vaccine strategy. CORAVAX has proven immunogenic and protective against SARS-CoV-2 in animal models. Here, we have screened adjuvants for the highest quality antibody titers, negated the concern of pre-existing rabies-vector immunity, and established its potential as a long-term COVID-19 vaccine. We have tested toll-like receptor 4 (TLR4) agonists, inflammasome activators, and alum adjuvants in CORAVAX and found TLR4-activating MPLA-AddaVax to have the greatest potential. We followed the humoral immune response to CORAVAX in mice with pre-existing rabies virus immunity and saw no significant differences compared to naive mice. We then followed the immune response to CORAVAX over several months and 1-year post-immunization. Mice maintained high antigen-specific serum antibody titers as well as long-lived antibody-secreting cells in the spleen and bone marrow. We believe this rabies-vector strategy combats the problem of waning immunity of other COVID-19 vaccines. These results together support CORAVAX’s potential during the ongoing COVID-19 pandemic.
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DOI: 10.1016/j.coviro.2020.09.003
发表时间: 2020-10
影响因子: 5.9
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发表时间: 2019-04-15
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影响因子: 9.2
作者:
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