COVID-19 has caused over 2 從們million deaths globally with th線吧e numbers increasing見坐 at an alarming rate. A monum鐵的ental worldwide vac飛西cination program is being rolled ou厭地t with several companies includi歌請ng AstraZeneca/Oxford生匠 University, Pf從坐izer/BioNTech and Moderna leading the 低高way and offering rea視北l hope of slowing the pandemic.朋爸 Upon SARS-CoV-2 infection, the huma時答n immune system responds with CD4+ cells and CD8+ T cells concomitant with neutr林路alising antibodies that 睡少have been shown to pe跳新rsist for several months (1,2).關做 These antibodies pr林懂edominantly target the SARS-Co鐵白V-2 spike (S) protein哥線 in the receptor bindin吃但g domain (RBD) (3). Gi師務ven the emergence of SARS-CoV-2 varian歌北ts and that human coronaviruses ca用視n undergo antigenic evolut很友ion that compromises neutra嗎計lizing antibody immunity (4)快明, it is essent技鄉ial to determine whether SARS-C物頻oV-2 variants w喝看ill confer immune avoidance.
A D614G SARS-CoV-2 variant tha近店t exhibits enhanced transmission has l也算ed to this variant dominati鄉到ng the original strain (5) alth姐海ough the successful vaccine trials 喝醫confirm this mutation unlikely im體間pacts on antibody-m畫睡ediated neutralisatio會店n. Two recent SARS服唱-CoV-2 variants 視費have received a lot of attention長懂. B.1.1.7, designated Vari男短ant of Concern 202012/01 (VOC),很請 possesses a N501Y mut做房ation that increases ACE2 binding 林坐and infectivity (6,7). Thi可微s, together with a P618H mutat弟件ion, deletion of spike protein am雨刀ino acids 69 and 70 (Δ69-70) and severa市唱l additional mutations have yielded a p放是henotypic change that ma農懂nifests in a high兵了er rate of transmission. These mutati身文ons do not seem to off在理er a selective advant到話age for evading immune dete內也ction (8), however, very recent repo街謝rts suggest this variant is mor器腦e deadly (9). 吃兵; A SARS-CoV-2 variant originating in 腦議South Africa termed 501Y.V2 possesses家答 9 changes in the從綠 spike protein alone; both in the RBD d會了omain (K417N, E484K and N冷務501Y) and N-ter說哥minal domain (NTD民相; L18F, D80A, D215G年得, Δ242-244, and R246I) (10). This l業訊ocalised cluster of機資 mutations and in partic城中ular E484K, also detected in a城到 variant in Brazil如如 (11), appear to increase the c雪筆hances of avoiding 美公antibody neutralisation (12器在).
In a recent publication by Wibn影機er et al, the 50請光1Y.V2 variant was assessed for its子我 sensitivity to n慢好eutralisation by monoclonal antibodie務門s using structural modelling,還林 ELISA and lentivirus pseudotyping 靜術(13). By characterising the interacti村商on between antibodies and書物 the RBD of SAR船友S-CoV-2, several anti畫月bodies with epitopes子大 centred on amino acid changes f到空ound in the 501Y.V2 variant were ass行低essed by ELISA. While the RBD of ori算弟ginal SARS-CoV-2 bound to the antibod我河ies, recombinant RBD protein co船子ntaining mutati就器ons found in 501Y.V2 was unabl工小e to do so. Key residu空雜es identified that impaired 黑遠antibody neutralis讀兒ation included K417, E484, R102畫現, R246 and Δ242-244. These fin錯店dings were supported by neutralisation場能 assays where lentivirus p作快seudotyped to express SARS-C妹雨oV-2 S protein was added to商愛 HEK293T cells ex舞站pressing human ACE2 receptor. N來舞eutralisation of viral transduct少鐵ion was assessed by the abil說票ity of monoclonal antibodies to in和能hibit viral tran我嗎sduction as measured by luci鐘自ferase activity. T照技o further evaluate mutations found in 5也購01Y.V2 S protein, polyclonal 公雜plasma/serum from patients infected wit制術h severe COVID-19知快 were assayed for neutralisation 自友activity. While plasma from these patie但慢nts neutralised the SARS-CoV-去劇2 D614G lineage計玩, almost 50% of sa呢土mples failed to neutralise th報時e 501Y.V2 lineage. Psuedotyping lentivi船新rus with just three of t計農he known mutations; K417N,影快 E484K and N501Y rev媽聽ealed a loss of a火機ctivity further highlighting the imp體務ortance of these residues媽音.
While considerably more studies著城 are needed to fully evalu木農ate new SARS-CoV-2 var風區iants, particula北友rly the efficacy o請市f T cell responses, the金民 role of non-neutralising antibodi窗生es and inter/intra-person heterogene書窗ity, the data here suggest that new var冷外iants pose a signif志醫icant risk of immune surv務木eillance escape and re-嗎術infection. If so, the colossal R&愛不amp;D effort needs to continue 她如to ensure we have習音 a vaccine platform that can 麗頻adapt and ultimately succeed.
VectorBuilderoffers a number術林 of COVID-19 solutions including recombinant Coronavirus vec能從tors for reconstitutio國鐵n of wild type and variant vir和快uses, pseudotyped lentivirus and VSV with S protein from wild type, 綠議D614G, B.1.1.7 and 501Y.V2 and筆國 cell lines for isolation and propagation of v日自irus. Contact us to find out more o我一r help designing your c森到ustom vectors.
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