Intranasal immunization with avian paramyxovirus type 3 expressing SARS-CoV-2 spike protein protects hamsters against SARS-CoV-2.
Intranasal immunization with avian paramyxovirus type 3 expressing SARS-CoV-2 spike protein protects hamsters against SARS-CoV-2.
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DOI：
10.1038/s41541-022-00493-x
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发表时间：
2022-06-28
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
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作者：
目前针对严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）的疫苗是经肠外注射的，似乎对下呼吸道比上呼吸道更有保护作用。需要直接刺激呼吸道免疫和全身免疫的疫苗。我们使用禽副粘病毒3型（APMV3）作为鼻内疫苗载体表达SARS-CoV-2刺突(S)蛋白。人类缺乏预先存在的免疫力和宿主范围限制导致的衰减使APMV3成为感兴趣的载体。SARS-CoV-2 S蛋白通过6个脯氨酸取代（S- 6p）而不是大多数候选疫苗中使用的两个脯氨酸取代来稳定其融合前构象，从而提高了稳定性。表达S- 6p的APMV3 （APMV3/S- 6p）在鸡胚蛋中复制到高滴度，遗传稳定，而表达非稳定S或S- 2p的APMV3则不稳定。在仓鼠中，单次鼻内剂量的APMV3/S- 6p诱导了对S蛋白及其受体结合域的强血清IgG和IgA反应，以及对SARS-CoV-2分离株WA1/2020（谱系a）的强血清中和抗体反应。免疫APMV3/ s - 6p的仓鼠血清也能有效中和α和β变异。接种WA1/2020的免疫仓鼠没有表现出在空载体免疫对照组中观察到的体重减轻和肺部炎症；与对照组的大量复制相比，免疫动物上呼吸道和下呼吸道的SARS-CoV-2复制较低或检测不到。因此，单次鼻内剂量的APMV3/S-6P具有高度的免疫原性和对SARS-CoV-2攻击的保护作用，表明APMV3/S-6P适合临床开发。
Current vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are administered parenterally and appear to be more protective in the lower versus the upper respiratory tract. Vaccines are needed that directly stimulate immunity in the respiratory tract, as well as systemic immunity. We used avian paramyxovirus type 3 (APMV3) as an intranasal vaccine vector to express the SARS-CoV-2 spike (S) protein. A lack of pre-existing immunity in humans and attenuation by host-range restriction make APMV3 a vector of interest. The SARS-CoV-2 S protein was stabilized in its prefusion conformation by six proline substitutions (S-6P) rather than the two that are used in most vaccine candidates, providing increased stability. APMV3 expressing S-6P (APMV3/S-6P) replicated to high titers in embryonated chicken eggs and was genetically stable, whereas APMV3 expressing non-stabilized S or S-2P were unstable. In hamsters, a single intranasal dose of APMV3/S-6P induced strong serum IgG and IgA responses to the S protein and its receptor-binding domain, and strong serum neutralizing antibody responses to SARS-CoV-2 isolate WA1/2020 (lineage A). Sera from APMV3/S-6P-immunized hamsters also efficiently neutralized Alpha and Beta variants of concern. Immunized hamsters challenged with WA1/2020 did not exhibit the weight loss and lung inflammation observed in empty-vector-immunized controls; SARS-CoV-2 replication in the upper and lower respiratory tract of immunized animals was low or undetectable compared to the substantial replication in controls. Thus, a single intranasal dose of APMV3/S-6P was highly immunogenic and protective against SARS-CoV-2 challenge, suggesting that APMV3/S-6P is suitable for clinical development.
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影响因子：
3
作者：
Espitia CM;Zhao W;Saldarriaga O;Osorio Y;Harrison LM;Cappello M;Travi BL;Melby PC
通讯作者：
Melby PC
DOI：
10.1056/nejmoa2113017
发表时间：
2021-11-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
El Sahly HM;Baden LR;Essink B;Doblecki-Lewis S;Martin JM;Anderson EJ;Campbell TB;Clark J;Jackson LA;Fichtenbaum CJ;Zervos M;Rankin B;Eder F;Feldman G;Kennelly C;Han-Conrad L;Levin M;Neuzil KM;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Polakowski L;Mascola JR;Ledgerwood JE;Graham BS;August A;Clouting H;Deng W;Han S;Leav B;Manzo D;Pajon R;Schödel F;Tomassini JE;Zhou H;Miller J;COVE Study Group
通讯作者：
COVE Study Group
DOI：
10.1056/nejmoa2109072
发表时间：
2021-10-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bergwerk M;Gonen T;Lustig Y;Amit S;Lipsitch M;Cohen C;Mandelboim M;Levin EG;Rubin C;Indenbaum V;Tal I;Zavitan M;Zuckerman N;Bar-Chaim A;Kreiss Y;Regev-Yochay G
通讯作者：
Regev-Yochay G
影响因子：
5.4
作者：
DiNapoli, Joshua M.;Nayak, Baibaswata;Bukreyev, Alexander
通讯作者：
Bukreyev, Alexander
影响因子：
5.5
作者：
DiNapoli, Joshua M.;Yang, Lijuan;Samal, Siba K.;Murphy, Brian R.;Collins, Peter L.;Bukreyev, Alexander
通讯作者：
Bukreyev, Alexander