Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2.
Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2.
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单独的和作为针对SARS-CoV-2的异源加强剂的0微米特异性mRNA疫苗接种。
DOI：
10.1038/s41467-022-30878-4
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发表时间：
2022-06-06
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
SARS-CoV-2的Omicron变体最近席卷了地球仪，并显示出高水平的免疫逃避。在这里，我们产生了一种0微米特异性脂质纳米颗粒（LNP）mRNA疫苗候选物，并测试了其在动物中的活性，无论是单独的还是作为WT mRNA疫苗的异源加强剂。我们的0 μ m特异性LNP-mRNA疫苗在未接种过疫苗的小鼠中激发了强烈的抗体应答。接受两剂量WT LNP-mRNA的小鼠在加强后两周显示针对Omicron的中和效力比WT降低> 40倍，其在3个月后进一步降低至背景水平。在注射后两周，WT或Omicron LNP-mRNA加强剂使WT LNP-mRNA接种的小鼠针对Omicron的减弱的抗体应答增加40倍。有趣的是，异源Omicron加强剂针对Omicron变体的中和滴度比同源WT加强剂高10-20倍，针对Delta变体的滴度相当。所有三种类型的疫苗接种，包括Omicron单独接种、WT加强接种和Omicron加强接种，均引发针对SARS-CoV-2 WA-1、Beta、Delta变体和SARS-CoV的广泛结合抗体应答。这些数据提供了单独和作为WT mRNA疫苗的异源加强剂的O微米特异性mRNA体内疫苗接种的直接评估。在本文中，作者表明，在用野生型（WT）脂质纳米颗粒（LNP）-mRNA疫苗免疫的小鼠中，Omicron中和抗体滴度随时间推移而下降，而WT或Omicron LNP-mRNA则显著增加，并且Omicron加强剂比WT加强剂引起更高的BA.1中和滴度。
The Omicron variant of SARS-CoV-2 recently swept the globe and showed high level of immune evasion. Here, we generate an Omicron-specific lipid nanoparticle (LNP) mRNA vaccine candidate, and test its activity in animals, both alone and as a heterologous booster to WT mRNA vaccine. Our Omicron-specific LNP-mRNA vaccine elicits strong antibody response in vaccination-naïve mice. Mice that received two-dose WT LNP-mRNA show a > 40-fold reduction in neutralization potency against Omicron than WT two weeks post boost, which further reduce to background level after 3 months. The WT or Omicron LNP-mRNA booster increases the waning antibody response of WT LNP-mRNA vaccinated mice against Omicron by 40 fold at two weeks post injection. Interestingly, the heterologous Omicron booster elicits neutralizing titers 10-20 fold higher than the homologous WT booster against Omicron variant, with comparable titers against Delta variant. All three types of vaccination, including Omicron alone, WT booster and Omicron booster, elicit broad binding antibody responses against SARS-CoV-2 WA-1, Beta, Delta variants and SARS-CoV. These data provide direct assessments of an Omicron-specific mRNA vaccination in vivo, both alone and as a heterologous booster to WT mRNA vaccine. Here the authors show that Omicron neutralizing antibody titers decline over time in mice immunized with a wild-type (WT) lipid nanoparticle (LNP)-mRNA vaccine and are robustly increased by WT or Omicron LNP-mRNA and that Omicron boosters elicit higher BA.1-neutralizing titer than WT boosters.
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影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
影响因子：
64.5
作者：
Dejnirattisai W;Zhou D;Ginn HM;Duyvesteyn HME;Supasa P;Case JB;Zhao Y;Walter TS;Mentzer AJ;Liu C;Wang B;Paesen GC;Slon-Campos J;López-Camacho C;Kafai NM;Bailey AL;Chen RE;Ying B;Thompson C;Bolton J;Fyfe A;Gupta S;Tan TK;Gilbert-Jaramillo J;James W;Knight M;Carroll MW;Skelly D;Dold C;Peng Y;Levin R;Dong T;Pollard AJ;Knight JC;Klenerman P;Temperton N;Hall DR;Williams MA;Paterson NG;Bertram FKR;Siebert CA;Clare DK;Howe A;Radecke J;Song Y;Townsend AR;Huang KA;Fry EE;Mongkolsapaya J;Diamond MS;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR
影响因子：
64.5
作者：
Hoffmann M;Krüger N;Schulz S;Cossmann A;Rocha C;Kempf A;Nehlmeier I;Graichen L;Moldenhauer AS;Winkler MS;Lier M;Dopfer-Jablonka A;Jäck HM;Behrens GMN;Pöhlmann S
通讯作者：
Pöhlmann S
影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
影响因子：
64.5
作者：
Garcia-Beltran, Wilfredo F.;St Denis, Kerri J.;Balazs, Alejandro B.
通讯作者：
Balazs, Alejandro B.