Impact of an autophagy-inducing peptide on immunogenicity and protection efficacy of an adenovirus-vectored SARS-CoV-2 vaccine.
Impact of an autophagy-inducing peptide on immunogenicity and protection efficacy of an adenovirus-vectored SARS-CoV-2 vaccine.
复制标题
DOI：
10.1016/j.omtm.2023.06.009
复制
发表时间：
2023-09-14
期刊：
影响因子：
--
通讯作者：
Mittal SK
中科院分区：
文献类型：
--
作者：
Sayedahmed EE;Araújo MV;Silva-Pereira TT;Chothe SK;Elkashif A;Alhashimi M;Wang WC;Santos AP;Nair MS;Gontu A;Nissly R;Francisco de Souza Filho A;Tavares MS;Ayupe MC;Salgado CL;Donizetti de Oliveira Candido É;Leal Oliveira DB;Durigon EL;Heinemann MB;Morais da Fonseca D;Jagannath C;Sá Guimarães AM;Kuchipudi SV;Mittal SK
由于严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）新变种的不断产生，设计下一代疫苗以对抗SARS-CoV-2变种所构成的威胁至关重要。我们开发了基于人腺病毒（HAd）载体的疫苗（HAd-Spike/C5和HAd-Spike），其分别表达SARS-CoV-2的完整Spike（S）蛋白和自噬诱导肽C5（AIP-C5）。小鼠或金黄色叙利亚仓鼠鼻内（i.n.）与HAd-Spike接种组相比，HAd-Spike/C5接种组诱导相似水平的S特异性体液免疫应答和显著更高水平的S特异性细胞介导的免疫（CMI）应答。这些结果表明，包含AIP-C5诱导增强的S特异性CMI应答和针对SARS-CoV-2变体的相似水平的病毒中和滴度。为了研究免疫保护效果，将金黄地鼠i.n.用SARS-CoV-2攻击HAd-Spike/C5或HAd-Spike。攻毒后3、5、7和14天采集肺和鼻甲。与模拟或空载体接种组相比，在免疫组中观察到发病率、病毒滴度和肺组织病理学评分显著降低。总体而言，与HAd-Spike组相比，HAd-Spike/C5组的保护效果略好。Mittal和他的同事证明，表达SARS-CoV-2刺突蛋白和自噬诱导肽C5（AIP-C5）的腺病毒载体增强了细胞介导的免疫反应，这对于靶向SARS-CoV-2变体至关重要。在免疫的仓鼠中观察到改善的免疫应答和保护，表明AIP-C5在疫苗设计中的重要性。
Because of continual generation of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is critical to design the next generation of vaccines to combat the threat posed by SARS-CoV-2 variants. We developed human adenovirus (HAd) vector-based vaccines (HAd-Spike/C5 and HAd-Spike) that express the whole Spike (S) protein of SARS-CoV-2 with or without autophagy-inducing peptide C5 (AIP-C5), respectively. Mice or golden Syrian hamsters immunized intranasally (i.n.) with HAd-Spike/C5 induced similar levels of S-specific humoral immune responses and significantly higher levels of S-specific cell-mediated immune (CMI) responses compared with HAd-Spike vaccinated groups. These results indicated that inclusion of AIP-C5 induced enhanced S-specific CMI responses and similar levels of virus-neutralizing titers against SARS-CoV-2 variants. To investigate the protection efficacy, golden Syrian hamsters immunized i.n. either with HAd-Spike/C5 or HAd-Spike were challenged with SARS-CoV-2. The lungs and nasal turbinates were collected 3, 5, 7, and 14 days post challenge. Significant reductions in morbidity, virus titers, and lung histopathological scores were observed in immunized groups compared with the mock- or empty vector-inoculated groups. Overall, slightly better protection was seen in the HAd-Spike/C5 group compared with the HAd-Spike group. Mittal and his colleagues demonstrated that the adenovirus vector expressing the spike protein of SARS-CoV-2 with autophagy-inducing peptide C5 (AIP-C5) enhances cell-mediated immune responses, which is critical for targeting SARS-CoV-2 variants. Improved immune responses and protection were observed in immunized hamsters, suggesting the importance of AIP-C5 in vaccine design.
登录
查看更多内容
影响因子：
9.4
作者：
Addetia A;Crawford KHD;Dingens A;Zhu H;Roychoudhury P;Huang ML;Jerome KR;Bloom JD;Greninger AL
通讯作者：
Greninger AL
DOI：
10.1016/j.xcrm.2021.100372
发表时间：
2021-08-17
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Khan A;Sayedahmed EE;Singh VK;Mishra A;Dorta-Estremera S;Nookala S;Canaday DH;Chen M;Wang J;Sastry KJ;Mittal SK;Jagannath C
通讯作者：
Jagannath C
影响因子：
3.8
作者：
GRAHAM, FL;SMILEY, J;NAIRN, R
通讯作者：
NAIRN, R
DOI：
10.1056/nejmsr2105280
发表时间：
2021-07-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Krause PR;Fleming TR;Longini IM;Peto R;Briand S;Heymann DL;Beral V;Snape MD;Rees H;Ropero AM;Balicer RD;Cramer JP;Muñoz-Fontela C;Gruber M;Gaspar R;Singh JA;Subbarao K;Van Kerkhove MD;Swaminathan S;Ryan MJ;Henao-Restrepo AM
通讯作者：
Henao-Restrepo AM
DOI：
10.1016/s2666-5247(21)00267-6
发表时间：
2022-01
期刊：
The Lancet. Microbe
影响因子：
--
作者：
Cromer D;Steain M;Reynaldi A;Schlub TE;Wheatley AK;Juno JA;Kent SJ;Triccas JA;Khoury DS;Davenport MP
通讯作者：
Davenport MP