Oral Administration of Universal Bacterium-Vectored Nucleocapsid-Expressing COVID-19 Vaccine is Efficacious in Hamsters.
Oral Administration of Universal Bacterium-Vectored Nucleocapsid-Expressing COVID-19 Vaccine is Efficacious in Hamsters.
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DOI：
10.1128/spectrum.05035-22
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发表时间：
2023-03-14
影响因子：
3.7
通讯作者：
Horwitz, Marcus A.
中科院分区：
文献类型：
--
作者：
Jia, Qingmei;Bielefeldt-Ohmann, Helle;Maison, Rachel M.;Hartwig, Airn;Maslesa-Galic, Sasa;Bowen, Richard A.;Horwitz, Marcus A.
关键词：
口服廉价的COVID-19（2019冠状病毒病）疫苗可以大大提高免疫接种率，特别是在低收入和中等收入国家。之前，我们描述了一种潜在的通用COVID-19疫苗rLVS ΔcapB/MN，包括复制细菌载体LVS（活疫苗株）ΔcapB，表达高度保守的SARS-CoV-2（严重急性呼吸综合征冠状病毒2）膜和核衣壳(N)蛋白，当皮内或鼻内给药时，保护仓鼠在高剂量SARS-CoV-2呼吸道攻击后免受严重的COVID-19样疾病。在这里，我们表明口服疫苗也可以防止高剂量SARS-CoV-2呼吸道攻击；其保护作用可与皮内、鼻内或皮下给药相媲美。仓鼠被保护免受严重的体重减轻和肺部病理，并降低口咽和肺部病毒滴度。该疫苗在小鼠中诱导脾脏和肺细胞干扰素γ响应于N蛋白刺激，对体重减轻和组织病理学的保护作用与攻毒前血清抗N th1偏态IgG （IgG2/3）相关。因此，rLVS ΔcapB/MN具有作为口服通用COVID-19疫苗的潜力。2019冠状病毒病大流行在全球范围内继续肆虐，进入第四个年头。为了最有效地保护世界人口免受严重疾病、住院和死亡的威胁，需要一种疫苗，这种疫苗能够抵抗病原体SARS-CoV-2迅速出现的病毒变体，制造、储存和运输成本低廉，并且易于管理。理想情况下，这种疫苗能够口服，特别是在世界上资源贫乏的国家，那里缺乏针头、注射器和训练有素的人员来注射疫苗。在这里，我们表明，口服符合所有这些标准的细菌载体疫苗可以保护自然易感的叙利亚仓鼠在高剂量SARS-CoV-2呼吸道攻击后免受严重的covid -19样疾病，包括严重的体重减轻和肺部病理。由于该疫苗是基于诱导对高度保守的SARS-CoV-2膜和核衣壳蛋白的免疫，而不是对快速突变的Spike蛋白的免疫，因此它应该对新出现的SARS-CoV-2变体保持抗性。
Oral delivery of an inexpensive COVID-19 (coronavirus disease 2019) vaccine could dramatically improve immunization rates, especially in low- and middle-income countries. Previously, we described a potential universal COVID-19 vaccine, rLVS ΔcapB/MN, comprising a replicating bacterial vector, LVS (live vaccine strain) ΔcapB, expressing the highly conserved SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) membrane and nucleocapsid (N) proteins, which, when administered intradermally or intranasally, protects hamsters from severe COVID-19-like disease after high-dose SARS-CoV-2 respiratory challenge. Here, we show that oral administration of the vaccine also protects against high-dose SARS-CoV-2 respiratory challenge; its protection is comparable to that of intradermal, intranasal, or subcutaneous administration. Hamsters were protected against severe weight loss and lung pathology and had reduced oropharyngeal and lung virus titers. Protection against weight loss and histopathology by the vaccine, which in mice induces splenic and lung cell interferon gamma in response to N protein stimulation, was correlated in hamsters with pre-challenge serum anti-N TH1-biased IgG (IgG2/3). Thus, rLVS ΔcapB/MN has potential as an oral universal COVID-19 vaccine. IMPORTANCE The COVID-19 pandemic continues to rage into its fourth year worldwide. To protect the world’s population most effectively from severe disease, hospitalization, and death, a vaccine is needed that is resistant to rapidly emerging viral variants of the causative agent SARS-CoV-2, inexpensive to manufacture, store, and transport, and easy to administer. Ideally, such a vaccine would be capable of oral administration, especially in resource-poor countries of the world where there are shortages of needles, syringes and trained personnel to administer injectable vaccines. Here, we show that oral administration of a bacterium-vectored vaccine meeting all these criteria protects naturally susceptible Syrian hamsters from severe COVID-19-like disease, including severe weight loss and lung pathology, after high-dose SARS-CoV-2 respiratory challenge. As the vaccine is based upon inducing immunity to highly conserved SARS-CoV-2 membrane and nucleocapsid proteins, as opposed to the rapidly mutating Spike protein, it should remain resistant to newly emerging SARS-CoV-2 variants.
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影响因子：
9.2
作者：
Kleanthous H;Silverman JM;Makar KW;Yoon IK;Jackson N;Vaughn DW
通讯作者：
Vaughn DW
影响因子：
9.2
作者：
Jia Q;Bielefeldt-Ohmann H;Maison RM;Masleša-Galić S;Cooper SK;Bowen RA;Horwitz MA
通讯作者：
Horwitz MA
影响因子：
3.1
作者：
Jia, Qingmei;Lee, Bai-Yu;Horwitz, Marcus A.
通讯作者：
Horwitz, Marcus A.
影响因子：
64.8
作者：
Meng B;Abdullahi A;Ferreira IATM;Goonawardane N;Saito A;Kimura I;Yamasoba D;Gerber PP;Fatihi S;Rathore S;Zepeda SK;Papa G;Kemp SA;Ikeda T;Toyoda M;Tan TS;Kuramochi J;Mitsunaga S;Ueno T;Shirakawa K;Takaori-Kondo A;Brevini T;Mallery DL;Charles OJ;CITIID-NIHR BioResource COVID-19 Collaboration;Genotype to Phenotype Japan (G2P-Japan) Consortium;Ecuador-COVID19 Consortium;Bowen JE;Joshi A;Walls AC;Jackson L;Martin D;Smith KGC;Bradley J;Briggs JAG;Choi J;Madissoon E;Meyer KB;Mlcochova P;Ceron-Gutierrez L;Doffinger R;Teichmann SA;Fisher AJ;Pizzuto MS;de Marco A;Corti D;Hosmillo M;Lee JH;James LC;Thukral L;Veesler D;Sigal A;Sampaziotis F;Goodfellow IG;Matheson NJ;Sato K;Gupta RK
通讯作者：
Gupta RK
DOI：
10.1016/j.xcrm.2021.100354
发表时间：
2021-07-20
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Cohen KW;Linderman SL;Moodie Z;Czartoski J;Lai L;Mantus G;Norwood C;Nyhoff LE;Edara VV;Floyd K;De Rosa SC;Ahmed H;Whaley R;Patel SN;Prigmore B;Lemos MP;Davis CW;Furth S;O'Keefe JB;Gharpure MP;Gunisetty S;Stephens K;Antia R;Zarnitsyna VI;Stephens DS;Edupuganti S;Rouphael N;Anderson EJ;Mehta AK;Wrammert J;Suthar MS;Ahmed R;McElrath MJ
通讯作者：
McElrath MJ