The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines

Liu, Yafei; Arase, Noriko; Kishikawa, Jun-ichi; Hirose, Mika; Li, Songling; Tada, Asa; Matsuoka, Sumiko; Arakawa, Akemi; Akamatsu, Kanako; Ono, Chikako; Jin, Hui; Kishida, Ken; Nakai, Wataru; Kohyama, Masanori; Nakagawa, Atsushi; Yamagishi, Yoshiaki; Nakagami, Hironori; Kumanogoh, Atsushi; Matsuura, Yoshiharu; Standley, Daron M.; Kato, Takayuki; Okada, Masato; Fujimoto, Manabu; Arase, Hisashi

doi:10.1101/2021.08.22.457114

Cited by 31 publications

(45 citation statements)

References 67 publications

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“…6A). The conformational changes in NTD loops and glycan shield provide an explanation for the escape from the NTD-specific nAbs 21 and the markedly reduced efficacies of the convalescent and vaccine-elicited sera 25,26 .…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism by which NTD-specific nAbs neutralize SARS-CoV-2 infection is not well understood; however, it is well established that several VOC-and VOI-associated NTD mutations significantly reduce or completely abolish nAb neutralization thus leading to immunity escape 16,[18][19][20] . Specifically, a recent study reports complete escape of the Delta variant from a panel of 16 NTD-specific nAbs 21 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structure-activity relationships of B.1.617 and other SARS-CoV-2 spike variants

Yang

Chang

et al. 2021

Preprint

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The surge of COVID-19 infection cases is spurred by emerging SARS-CoV-2 variants such as B.1.617. Here we report 38 cryo-EM structures, corresponding to the spike protein of the Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Kappa (B.1.617.1) variants in different functional states with and without its receptor, ACE2. Mutations on the N-terminal domain not only alter the conformation of the highly antigenic supersite of the Delta variant, but also remodel the glycan shield by deleting or adding N-glycans of the Delta and Gamma variants, respectively. Substantially enhanced ACE2 binding was observed for all variants, whose mutations on the receptor binding domain modulate the electrostatics of the binding interfaces. Despite their abilities to escape host immunity, all variants can be potently neutralized by three unique antibodies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structure-activity relationships of B.1.617 and other SARS-CoV-2 spike variants

Yang

Chang

et al. 2021

Preprint

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“…This will allow a more rapid evolution of variants with mutations which are likely to escape both convalescent and vaccine immunity. (Liu et al, 2021) Herd immunity is unlikely to ever be achieved since the medical community is unable to vaccinate as many people as possible in a short period of time in both the U.S. and all across the world. (Aschwanden, 2021) Given the results from estimating the empirical model specified in equation 1, we are in agreement with the current literature regarding the factors that determine the variation of vaccine hesitancy in different states within the United States.…”

Section: Discussionmentioning

confidence: 99%

“…The mRNA vaccines remain the most effective against the delta variants. (Liu et al, 2021). Other factors which will lead to more infections are laws in Florida and Texas against mask and vaccine mandates in Florida and Texas.…”

Section: Vaccine Development and Availabilitymentioning

confidence: 99%

An Analysis of the Determinants of Vaccine Hesitancy. Can the World Learn from the US Experience?

Kahai¹,

Herrington²,

Folino³

2021

IBES

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While efforts to vaccinate the general public have been trending in a positive direction, Vaccine Hesitancy is a global issue. Many infectious disease physicians, epidemiologists, and Public Health Authorities fear that Vaccine Hesitancy will indefinitely prolong the pandemic, as the Delta Variant currently ravages through the unvaccinated population. In an attempt to understand this global phenomenon, we looked at the United States’ vaccine rollout. In particular, we examined the determinants of vaccine hesitancy in the USA. Our empirical model reveals that Vaccine Hesitancy is significantly impacted by factors such as Median Income, Political Affiliation, Percentage of population that is White/Caucasian, Total Cases, Individuals without Health Insurance, and Education level. We use data from all 50 states in the US. Policy makers in other countries can greatly benefit from the findings of our empirical results. Some incentive structures should be introduced as quickly as possible to achieve a high vaccination rate in the country. Our goal is to use the United State’s experience of Vaccine Hesitancy as a baseline of sorts for the greater global community to understand, and reduce hesitancy in their vaccine rollouts.

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“…The mutations in the NTD, such as T19R, G142D, E156G, F157del and R158del are involved in the enhanced infectivity by the BNT162b2-immune sera. The neutralizing activity of sera from vaccinated individuals as well as convalescent COVID-19 patients decreases for the Delta variant compared to the wildtype SARS-CoV-2 [15][16][17]. Both ACE2 RBD and NTD mutations should be evaluated on all positive samples to understand the pathogenicity of the SARS-CoV-2 variants.…”

Section: Sars-mentioning

confidence: 99%

A Routine Sanger Sequencing Target Specific Mutation Assay For SARS-CoV-2 Variants Of Concern And Interest

Lee¹

2021

Preprint

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As SARS-CoV-2 continues to spread among human populations, genetic changes occur and accumulate in the circulating virus. Some of these genetic changes have caused amino acid mutations, including deletions, which may have potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics. Considerable efforts have been made to categorize the amino acid mutations of the angiotensin-converting enzyme 2 (ACE2) receptor binding domain (RBD) of the spike (S) protein along with certain mutations in other regions within the S protein as specific variants in an attempt to study the relationship between these mutations and the biological behavior of the virus. However, the currently used whole genome sequencing surveillance technologies can test only a small fraction of the positive specimens with high viral loads and often generate uncertainties in nucleic acid sequencing that needs additional verification for precision determination of mutations. This article introduces a generic protocol to routinely sequence a 437-bp nested RT-PCR cDNA amplicon of the ACE2 RBD and a 490-bp nested RT-PCR cDNA amplicon of the N-terminal domain (NTD) of the S gene for detection of the amino acid mutations needed for accurate determination of all variants of concern and variants of interest according to the definitions published by the U.S. Centers for Disease Control and Prevention. This protocol was able to amplify both nucleic acid targets into cDNA amplicons to be used as templates for Sanger sequencing on all 16 clinical specimens that were positive for SARS-CoV-2.

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The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines

Cited by 31 publications

References 67 publications

Structure-activity relationships of B.1.617 and other SARS-CoV-2 spike variants

Structure-activity relationships of B.1.617 and other SARS-CoV-2 spike variants

An Analysis of the Determinants of Vaccine Hesitancy. Can the World Learn from the US Experience?

A Routine Sanger Sequencing Target Specific Mutation Assay For SARS-CoV-2 Variants Of Concern And Interest

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