Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda

  1. Mónica L. Acevedo
  2. Luis Alonso-Palomares
  3. Andrés Bustamante
  4. Aldo Gaggero
  5. Fabio Paredes
  6. Claudia P. Cortés
  7. Fernando Valiente-Echeverría
  8. Ricardo Soto-Rifo

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Abstract

Background

The newly described SARS-CoV-2 lineage C.37 was recently classified as a variant of interest by the WHO (Lambda variant) based on its high circulation rates in South American countries and the presence of critical mutations in the spike protein. The impact of such mutations in infectivity and immune escape from neutralizing antibodies are entirely unknown.

Methods

We performed a pseudotyped virus neutralization assay and determined the impact of the Lambda variant on infectivity and immune escape using plasma samples from healthcare workers (HCW) from two centers in Santiago, Chile who received the two-doses scheme of the inactivated virus vaccine CoronaVac.

Results

We observed an increased infectivity mediated by the Lambda spike protein that was even higher than that of the D614G (lineage B) or the Alpha and Gamma variants. Compared to the Wild type (lineage A), neutralization was decreased by 3.05-fold for the Lambda variant while it was 2.33-fold for the Gamma variant and 2.03-fold for the Alpha variant.

Conclusions

Our results indicate that mutations present in the spike protein of the Lambda variant of interest confer increased infectivity and immune escape from neutralizing antibodies elicited by CoronaVac. These data reinforce the idea that massive vaccination campaigns in countries with high SARS-CoV-2 circulation must be accompanied by strict genomic surveillance allowing the identification of new isolates carrying spike mutations and immunology studies aimed to determine the impact of these mutations in immune escape and vaccines breakthrough.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Orson Mestanza

    Review 2: "Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda"

    This preprint describes gain-of-function properties for mutations defining the Lambda variant and the effectiveness of the CoronaVac vaccine against this variant. Reviewers consider the data reliable and require minor revision to clarify methodology.

  2. Rapid Reviews Infectious Diseases

    Alex Sigal

    Review 1: "Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda"

    This preprint describes gain-of-function properties for mutations defining the Lambda variant and the effectiveness of the CoronaVac vaccine against this variant. Reviewers consider the data reliable and require minor revision to clarify methodology.

  4. ScreenIT

    SciScore for 10.1101/2021.06.28.21259673: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: All participants signed an informed consent before any study procedure was undertaken.
    IRB: Ethical approval: The study protocol was approved by the Ethics Committee of the Faculty of Medicine at Universidad de Chile (Projects N° 0361-2021 and N° 096-2020) and Clínica Santa Maria (Project N°132604-21).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Different amounts of pseudotyped viruses (as determined by the levels of the HIV-1 p24 protein) were used to infect HEK-ACE2 cells and 48 hours later, firefly luciferase activity was measured using the Luciferase Assay Reagent (Promega) in a Glomax 96 Microplate luminometer (Promega).
    HEK-ACE2
    suggested: None
    HEK293T cells (not expressing ACE2) incubated with the pseudotyped virus (lineage A) were used as a negative control.
    HEK293T
    suggested: CCLV Cat# CCLV-RIE 1018, RRID:CVCL_0063)
    Recombinant DNA
    SentencesResources
    Briefly, HIV-1-based SARS-CoV-2 pseudotypes were produced in HEK293T cells by transfecting the pNL4.3-ΔEnv-Luc together with the corresponding pCDNA-SARS-CoV-2 Spike coding vector in a 1:1 molar ratio.
    pNL4.3-ΔEnv-Luc
    suggested: None
    pCDNA-SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    The percentage of neutralization for each dilution was calculated and the ID50 of each sample was calculated using GraphPad Prism version 9.0.1.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  5. Version published to 10.1101/2021.06.28.21259673v1 on medRxiv