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The Lambda variant of SARS-CoV-2 has a better chance than the Delta variant to escape vaccines.

ABSTRACT: The newly emerging variants of SARS-CoV-2 from India (Delta variant) and South America (Lambda variant) have led to a higher infection rate of either vaccinated or unvaccinated people. We found that sera from Pfizer-BioNTech vaccine remain high reactivity toward the receptor binding domain (RBD) of Delta variant while it drops dramatically toward that of Lambda variant. Interestingly, the overall titer of antibodies of Pfizer-BioNTech vaccinated individuals drops 3-fold after 6 months, which could be one of major reasons for breakthrough infections, emphasizing the importance of potential third boost shot. While a therapeutic antibody, Bamlanivimab, decreases binding affinity to Delta variant by ~20 fold, it fully lost binding to Lambda variant. Structural modeling of complexes of RBD with human receptor, Angiotensin Converting Enzyme 2 (ACE2), and Bamlanivimab suggest the potential basis of the change of binding. The data suggest possible danger and a potential surge of Lambda variant in near future.

SUBMITTER: Liu H

PROVIDER: S-EPMC8404886 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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The Lambda variant of SARS-CoV-2 has a better chance than the Delta variant to escape vaccines.

Liu Haolin H Wei Pengcheng P Zhang Qianqian Q Aviszus Katja K Linderberger Jared J Yang John J Liu Junfeng J Chen Zhongzhou Z Waheed Hassan H Reynoso Lyndon L Downey Gregory P GP Frankel Stephen K SK Kappler John J Marrack Philippa P Zhang Gongyi G

bioRxiv : the preprint server for biology 20210826

The newly emerging variants of SARS-CoV-2 from India (Delta variant) and South America (Lambda variant) have led to a higher infection rate of either vaccinated or unvaccinated people. We found that sera from Pfizer-BioNTech vaccine remain high reactivity toward the receptor binding domain (RBD) of Delta variant while it drops dramatically toward that of Lambda variant. Interestingly, the overall titer of antibodies of Pfizer-BioNTech vaccinated individuals drops 3-fold after 6 months, which cou ...[more]

PMID: 34462744

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Project description:BackgroundThe SARS-CoV-2 Delta variant was first identified in the U.S. in March 2021 and has rapidly become the predominant lineage across the U.S. due to increased transmissibility, immune evasion and vaccine breakthrough. The aim of this study was to better understand the genetic diversity and the potential impact of mutations observed in SARS-CoV-2 viruses circulating in the U.S. in vaccinated individuals.ResultsWhole genome sequencing was performed on thirty-four SARS-CoV-2 positive samples using the Oxford Nanopore MinION. Evolutionary genomic analysis revealed two novel mutations, ORF1b:V2354F and a premature stop codon, ORF7a:Q94*, identified in a cluster of SARS-CoV-2 Delta isolates collected from vaccinated individuals in Colorado. The ORF1b:V2354F mutation, corresponding to NSP15:V303F, may induce a conformational change and result in a disruption to a flanking beta-sheet structure. The premature stop codon, ORF7a:Q94*, truncates the transmembrane protein and cytosolic tail used to mediate protein transport. This may affect protein localization to the ER-Golgi. In addition to these novel mutations, the cluster of vaccinated isolates contain an additional mutation in the spike protein, at position 112, compared to the Delta variant defining mutations. This mutation, S112L, exists in isolates previously obtained in the U.S. The S112L mutation substitutes a bulky hydrophobic side chain for a polar side chain, which results in a non-conservative substitution within the protein that may affect antibody-binding affinity. Additionally, the vaccinated cluster of isolates contains non-synonymous mutations within ORF8 and NSPs which further distinguish this cluster from the respective ancestral Delta variant.ConclusionsThese results show there is an emerging sub-lineage of the ancestral Delta variant circulating in the U.S. As mutations emerge in constellations, those with a potentially beneficial advantage to the virus may continue to circulate while others will cease.

Project description:BackgroundSeveral vaccines with demonstrated efficacy for coronavirus disease 2019 (Covid-19) are available. The purpose of this study was to evaluate the COVID mRNA based and adenovector based vaccines' differential effectiveness during the time of circulation of the Delta variant and determine what impact this would have on population health and cost effectiveness.MethodsWe used de-identified claims in a research database that included vaccination status and Covid-positivity status. Individuals ≥18 years, fully vaccinated with Ad26.COV2·S/J&J/Janssen, mRNA-1273/Moderna, or BNT162b2/Pfizer-BioNTech by September 30, 2021, were included. Outcomes were SARS-CoV-2-infection, emergency department visits, outpatient visits, inpatient hospitalizations, intensive care unit (ICU) transfers, death, and hospice transfers through September 30, 2021.ResultsAmong ∼6.5 million fully vaccinated individuals in the UHC Medicare Advantage and our commercially insured research database, mRNA-1273 performed better than BNT162b2 for infection, composite-hospitalization (hospitalization/ICU transfer/hospice transfer/death), and composite-ICU transfer (ICU transfer/hospice transfer/death) caused by B.1.612.7 (delta) variant infection. 26 CE.COV2.S performed worse than BNT162b2 for infection, composite-hospitalization, and composite-ICU transfers. The number needed to vaccinate (NNV) with mRNA1273 to prevent one hospitalization at 90 days was 3130 compared to 26 CE.COV2·S and 15,472 compared to BNT162b2. The NNV with mRNA1273 to prevent one ICU transfer at 90 days was 6358 compared to 26 CE.COV2·S and 34,279 compared to BNT162b2. For every one million individuals vaccinated with BNT162b compared to mRNA-1273, the approximate incremental inpatient cost would be $405,000 and the approximate incremental ICU cost would be $662,000.ConclusionsThe two-dose mRNA vaccines' effectiveness significantly exceeded the single-dose Ad26.COV2·S vaccine's effectiveness from population health and cost-effectiveness perspectives. The mRNA1273 vaccine showed slightly more effectiveness than the BNT162b vaccine.

Dataset Information

The Lambda variant of SARS-CoV-2 has a better chance than the Delta variant to escape vaccines.

Publications

The Lambda variant of SARS-CoV-2 has a better chance than the Delta variant to escape vaccines.

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