Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines.
Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines.
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DOI：
10.1371/journal.ppat.1010885
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发表时间：
2022-10
期刊：
影响因子：
6.7
通讯作者：
Shattock, Robin J.
中科院分区：
文献类型：
--
作者：
Elliott, Tamara;Cheeseman, Hannah M.;Evans, Abbey B.;Day, Suzanne;McFarlane, Leon R.;O'Hara, Jessica;Kalyan, Mohini;Amini, Fahimah;Cole, Tom;Winston, Alan;Fidler, Sarah;Pollock, Katrina M.;Harker, James A.;Shattock, Robin J.
在对SARS-CoV-2刺突（S）糖蛋白的预先存在的免疫记忆的背景下，最佳疫苗接种策略是全球公共卫生的一个重要问题。为了解决这一问题，我们探索了SARS-CoV-2特异性体液和细胞免疫反应，以一种新的自扩增RNA（saRNA）疫苗，然后是英国授权的mRNA疫苗（BNT 162 b2）在有和没有先前的COVID-19的个体中，并将这些反应与那些只接受授权疫苗的人进行了比较。招募了35名接受saRNA（saRNA组）作为COVAC 1临床试验的一部分的受试者和另外40名仅接受授权的SARS-CoV-2疫苗（非saRNA组）的受试者。通过ELISA和抗中和试验测量野生型、Delta和Omicron变体的抗体应答。通过IFN-γ ELISpot和活化诱导标记（AIM）测定来测量细胞应答。每组中约有50%的人在接种疫苗前曾患有COVID-19，经PCR或ELISA抗体阳性证实。所有接受saRNA的人随后都接受了授权疫苗的完整疗程。大多数（83%）接受saRNA的基线COVID-19初治者在第二次接种后血清转化，以及既往COVID-19患者在saRNA疫苗接种后两周抗体滴度增加（中位数27倍），但与mRNA疫苗接种相比，滴度较低。在第二次授权的mRNA疫苗剂量后两周，与非saRNA或COVID-19初治的saRNA参与者相比，先前患有COVID-19的saRNA参与者的结合和中和抗体滴度显著更高。细胞应答在该组中再次最高，与仅接受mRNA疫苗的那些相比，刺突特异性CD 8 + T细胞的比例高于CD 4 + T细胞。这些发现表明增加的抗原暴露的免疫学益处，来自自然感染和疫苗接种两者，在接受saRNA和mRNA的异源疫苗接种的那些中特别明显。随着SARS-CoV-2变体的持续出现，从COVID-19中康复或免疫的人群不断增加。最佳的疫苗接种策略尚未确定，但越来越多的证据表明加强疫苗接种和自然感染后疫苗接种（混合免疫）的保护作用增强。在这项研究中，我们比较了接受新型自扩增RNA（saRNA）COVID-19疫苗的个体随后接受英国授权疫苗的免疫反应，以及单独接受授权疫苗的群体。每组中有一半的参与者已经从COVID-19中康复。我们发现，在先前患有COVID-19并接受saRNA加英国授权疫苗的患者中，在结合和中和抗体产生、针对关注变体（Delta和Omicron谱系变体）的中和宽度和T细胞应答方面具有上级的免疫应答。这些发现表明，使用不同疫苗平台的组合将先前的自然感染与针对COVID-19的疫苗接种相结合具有免疫学益处。
The optimal vaccination strategy to boost responses in the context of pre-existing immune memory to the SARS-CoV-2 spike (S) glycoprotein is an important question for global public health. To address this, we explored the SARS-CoV-2-specific humoral and cellular immune responses to a novel self-amplifying RNA (saRNA) vaccine followed by a UK authorised mRNA vaccine (BNT162b2) in individuals with and without previous COVID-19, and compared these responses with those who received an authorised vaccine alone. 35 subjects receiving saRNA (saRNA group) as part of the COVAC1 clinical trial and an additional 40 participants receiving an authorised SARS-CoV-2 vaccine only (non-saRNA group) were recruited. Antibody responses were measured by ELISA and a pseudoneutralisation assay for wildtype, Delta and Omicron variants. Cellular responses were measured by IFN-ƴ ELISpot and an activation induced marker (AIM) assay. Approximately 50% in each group had previous COVID-19 prior to vaccination, confirmed by PCR or antibody positivity on ELISA. All of those who received saRNA subsequently received a full course of an authorised vaccine. The majority (83%) of those receiving saRNA who were COVID-19 naïve at baseline seroconverted following the second dose, and those with previous COVID-19 had an increase in antibody titres two weeks following saRNA vaccination (median 27-fold), however titres were lower when compared to mRNA vaccination. Two weeks following the 2nd authorised mRNA vaccine dose, binding and neutralising antibody titres were significantly higher in the saRNA participants with previous COVID-19, compared to non-saRNA, or COVID-19 naive saRNA participants. Cellular responses were again highest in this group, with a higher proportion of spike specific CD8+ than CD4+ T cells when compared to those receiving the mRNA vaccine only. These findings suggest an immunological benefit of increased antigen exposure, both from natural infection and vaccination, particularly evident in those receiving heterologous vaccination with saRNA and mRNA. With the continuing emergence of SARS-CoV-2 variants of interest and of concern, there is an ever-growing population of people recovered from or immunised against COVID-19. The optimal vaccination strategies are still not established, but mounting evidence suggests enhanced protection from booster vaccination, and vaccination following natural infection (hybrid immunity). In this study we have compared immune responses in individuals who have received a novel self-amplifying RNA (saRNA) COVID-19 vaccine who have then subsequently received a UK authorised vaccine, and a group who received an authorised vaccine alone. Half the participants in each group had recovered from COVID-19. We found a superior immune response in those who had previous COVID-19 and received saRNA plus a UK authorised vaccine with regards to binding and neutralising antibody production, breadth of neutralisation against variants of concern (Delta and Omicron lineage variants) and T-cell responses. These findings suggest an immunological benefit of combining previous natural infection with vaccination against COVID-19 using a combination of different vaccine platforms.
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靶向SARS-COV-2的T细胞：通过感染，疫苗接种和对未来变体。
影响因子：
3.9
作者：
Nguyen THO;Cohen CA;Rowntree LC;Bull MB;Hachim A;Kedzierska K;Valkenburg SA
通讯作者：
Valkenburg SA
影响因子：
7.8
作者：
Buschmann MD;Carrasco MJ;Alishetty S;Paige M;Alameh MG;Weissman D
通讯作者：
Weissman D
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
24.8
作者：
Goel RR;Apostolidis SA;Painter MM;Mathew D;Pattekar A;Kuthuru O;Gouma S;Hicks P;Meng W;Rosenfeld AM;Dysinger S;Lundgreen KA;Kuri-Cervantes L;Adamski S;Hicks A;Korte S;Oldridge DA;Baxter AE;Giles JR;Weirick ME;McAllister CM;Dougherty J;Long S;D'Andrea K;Hamilton JT;Betts MR;Luning Prak ET;Bates P;Hensley SE;Greenplate AR;Wherry EJ
通讯作者：
Wherry EJ
影响因子：
7.7
作者：
Faulkner N;Ng KW;Wu MY;Harvey R;Margaritis M;Paraskevopoulou S;Houlihan C;Hussain S;Greco M;Bolland W;Warchal S;Heaney J;Rickman H;Spyer M;Frampton D;Byott M;de Oliveira T;Sigal A;Kjaer S;Swanton C;Gandhi S;Beale R;Gamblin SJ;McCauley JW;Daniels RS;Howell M;Bauer D;Nastouli E;Kassiotis G
通讯作者：
Kassiotis G