SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity

Motozono, Chihiro; Toyoda, Mako; Zahradník, Jiří; Saito, Akatsuki; Nasser, Hesham; Tan, Toong Seng; Ngare, Isaac; Kimura, Izumi; Uriu, Keiya; Kosugi, Yusuke; Yuan, Yue; Shimizu, Ryo; Ito, Jumpei; Torii, Shiho; Yonekawa, Akiko; Shimono, Nobuyuki; Nagasaki, Yoji; Minami, Ryoji; Toya, Takashi; Sekiya, Noritaka; Fukuhara, Takasuke; Matsuura, Yoshiharu; Schreiber, Gideon; Ikeda, Terumasa; Nakagawa, So; Ueno, Takamasa; Sato, Kei

doi:10.1016/j.chom.2021.06.006

Cited by 442 publications

(476 citation statements)

References 107 publications

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“…The D614G mutation is the hallmark of all variants, as it promotes viral spread by increasing the number of open S protomers in the homo-trimeric receptor complex [ 35 ]. The L452R mutation increases protein stability, viral infectivity, and potentially promotes viral replication [ 36 ].…”

Section: Consmentioning

confidence: 99%

Controversy surrounding the Sputnik V vaccine

Cazzola

Rogliani

Mazzeo

et al. 2021

Respiratory Medicine

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The Sputnik V COVID-19 vaccine is a member of the so-called vector vaccines and uses two different vectors (Ad26 priming and Ad5 boost) to reduce the risk of a reduction in the effectiveness of the vaccination. Real life data indicate an efficacy of the vaccine above 97%. Low cost and no need for ultra-cold storage temperature temperatures are other pluses of the Sputnik V vaccine. However, there are also several important shortcomings that must be considered such as the possible reduction of its immunogenicity in the presence of very high Ad5 neutralizing antibody titres and the decrease with age of the antibody titres neutralizing the virus. Furthermore, there is emerging documentation that Sputnik V has a reduced neutralizing capacity against the Beta variant and all variants with the spike protein carrying the E484K substitution. Nevertheless, due to its characteristics, Sputnik V could be another useful means of satisfying the need for mass vaccination. However, it is imperative to document the efficacy and safety of the Sputnik V vaccine in individuals with high pre-existing anti-Ad26 and Ad5-neutralizing antibody titres and in those under the age of 18 or older than 60 years and be certain that Sputnik V does not cause the rare development of immune thrombotic thrombocytopenia. It is hoped that the now widespread use of this vaccine will generate a large pragmatic real-world study with data accessible to anyone interested in verifying them.

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Section: Consmentioning

confidence: 99%

Controversy surrounding the Sputnik V vaccine

Cazzola

Rogliani

Mazzeo

et al. 2021

Respiratory Medicine

View full text Add to dashboard Cite

show abstract

“…The copyright holder for this preprint this version posted June 28, 2021. ; https://doi.org/10.1101/2021.06.21.21259010 doi: medRxiv preprint viral infectivity concomitantly reduce T-cell recognition through HLA*24:02 33 . Another study showed that some SARS-CoV-2 mutations in HLA-I-restricted epitopes resulted in lower binding to the HLA leading to reduced recognition by CD8 T-cells but there was little evidence of these mutations being disseminated 34 .…”

Section: Emerging Evidence Indicates That Hla-i-restricted Cd8 'Killer' T-cells Contribute To the Control Of Sars-mentioning

confidence: 99%

Emergence of immune escape at dominant SARS-CoV-2 killer T-cell epitope

Dolton

Rius

Hasan

et al. 2021

Preprint

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The adaptive immune system protects against infection via selection of specific antigen receptors on B-cells and T-cells. We studied the prevalent CD8 killer T-cell response mounted against SARS-CoV-2 Spike269-277 epitope YLQPRTFLL via the most frequent Human Leukocyte Antigen (HLA) class I worldwide, HLA A*02. The widespread Spike P272L mutation has arisen in five different SARS-CoV-2 lineages to date and was common in the B.1.177 lineage associated with establishing the second wave in Europe. The large CD8 T-cell response seen across a cohort of HLA A*02+ convalescent patients, comprising of over 120 different TCRs, failed to respond to the P272L variant suggesting that proline 272 dominates TCR contacts with this epitope. Additionally, sizable populations (0.01%-0.2%) of total CD8 T-cells from individuals vaccinated against SARS-CoV-2 stained with HLA A*02-YLQPRTFLL multimers but failed to bind to the P272L reagent. Viral escape at prevalent T-cell epitopes restricted by high frequency HLA may be particularly problematic when vaccine immunity is focussed on a single protein such as SARS-CoV-2 Spike and provides a strong argument for inclusion of multiple viral proteins in next generation vaccines and highlights the urgent need for monitoring T-cell escape in new SARS-CoV-2 variants.

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“…These findings are highly consistent with previous studies 20 . L452R mutation in the RBD was reported to increase SARS-CoV-2 infectivity and fusogenicity 21 . P681R, a highly conserved mutation in the B.1.617 lineages, also enhanced SARS-CoV-2 Spike-mediated cell-cell fusion 22 .…”

Section: Discussionmentioning

confidence: 99%

Reduced neutralization of SARS-CoV-2 B.1.617 variant by inactivated and RBD-subunit vaccine

Wei

Jin

et al. 2021

Preprint

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Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Spike protein that mediates coronavirus entry into host cells is a major target for COVID-19 vaccines and antibody therapeutics. However, multiple variants of SARS-CoV-2 have emerged, which may potentially compromise vaccine effectiveness. Using a pseudovirus-based assay, we evaluated SARS-CoV-2 cell entry mediated by the viral Spike B.1.617 and B.1.1.7 variants. We also compared the neutralization ability of monoclonal antibodies from convalescent sera and neutralizing antibodies (NAbs) elicited by CoronaVac (inactivated vaccine) and ZF2001 (RBD-subunit vaccine) against B.1.617 and B.1.1.7 variants. Our results showed that, compared to D614G and B.1.1.7 variants, B.1.617 shows enhanced viral entry and membrane fusion, as well as more resistant to antibody neutralization. These findings have important implications for understanding viral infectivity and for immunization policy against SARS-CoV-2 variants.

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SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity

Cited by 442 publications

References 107 publications

Controversy surrounding the Sputnik V vaccine

Controversy surrounding the Sputnik V vaccine

Emergence of immune escape at dominant SARS-CoV-2 killer T-cell epitope

Reduced neutralization of SARS-CoV-2 B.1.617 variant by inactivated and RBD-subunit vaccine

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