Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression

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Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Here, we confirmed that COVID-19 patients with cancer have low levels of antibodies against the spike (S) protein, a viral surface protein mediating the entry of SARS-CoV-2 into host cells, compared with COVID-19 patients without cancer. We developed an oncolytic herpes simplex virus-1 vector-based vaccine named oncolytic virus (OV)-spike. OV-spike induced abundant anti-S protein neutralization antibodies in both tumor-free and tumor-bearing mice, which inhibit infection of VSV-SARS-CoV-2 and wild-type (WT) live SARS-CoV-2 as well as the B.1.1.7 variant in vitro. In the tumor-bearing mice, OV-spike also inhibited tumor growth, leading to better survival in multiple preclinical tumor models than the untreated control. Furthermore, OV-spike induced anti-tumor immune response and SARS-CoV-2-specific T cell response without causing serious adverse events. Thus, OV-spike is a promising vaccine candidate for both preventing COVID-19 and enhancing the anti-tumor response.

One Sentence Summary

A herpes oncolytic viral vector-based vaccine is a promising vaccine with dual roles in preventing COVID-19 and treating tumor progression

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  1. SciScore for 10.1101/2021.06.07.447286: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Each patient had signed a consent as part of the IRB-approved protocol 20126 at City of Hope.
    IACUC: Ethics statement: All experiments using mice were conducted in compliance with federal, state, and local guidelines and with approval from the City of Hope Animal Care and Use Committee.
    Sex as a biological variableIn vivo mouse model: Six-to eight-week-old female BALB/c or C57BL/6 mice were purchased from Jackson Laboratories (Bar Harbor, Maine).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line AuthenticationContamination: All cell lines were routinely tested for the absence of mycoplasma using the MycoAlert Plus Mycoplasma Detection Kit from Lonza (Walkersville, MD).

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 viral nucleocapsid protein (NP) was detected using the anti-NP protein antibody (Cat. # PA5-81794, Thermo Fisher) diluted 1:10000 in 0.1% tween-20/1%BSA/PBS solution as a primary antibody, followed by detecting with an anti-rabbit secondary antibody (Cat. # ab6721, Abcam) at a 1:20,000 dilution.
    SARS-CoV-2 viral nucleocapsid protein (NP)
    suggested: None
    SARS-CoV-2 viral nucleocapsid protein (NP
    suggested: None
    anti-NP protein
    suggested: (Creative Diagnostics Cat# DPAB-DC4728, RRID:AB_2501850)
    anti-rabbit
    suggested: (Abcam Cat# ab6721, RRID:AB_955447)
    Mouse anti-spike antibody was diluted at 1:1000 in PBST containing 1% BSA and incubated with the membrane at 4°C overnight.
    anti-spike
    suggested: None
    HRP-conjugated goat anti-mouse IgG antibody (Cat. #05-4220, Invitrogen) was used for detection.
    anti-mouse IgG
    suggested: None
    After treatment with brefeldin A (Cat. # 420601, Biolegend) for 4 hours, the splenocytes were stained with the extracellular markers PE-Cy ™ 7 Hamster Anti-Mouse CD3e (Cat. # 552774, BD Pharmingen), APC-Cy7 Rat Anti-Mouse CD4 (Cat. # 552051, BD Pharmingen), and CD8 alpha Monoclonal Antibody (KT15), FITC (Cat. # MA5-16759.
    PE-Cy
    suggested: None
    Anti-Mouse CD3e
    suggested: None
    CD4
    suggested: (BD Biosciences Cat# 552051, RRID:AB_394331)
    CD8
    suggested: (Thermo Fisher Scientific Cat# MA5-16759, RRID:AB_2538242)
    Intravenous injection of OV-spike induces anti-S antibody production in mouse sera.
    anti-S
    suggested: None
    No significant difference of anti-S-specific antibody production between the tumor models. Fig. S6.
    anti-S-specific
    suggested: None
    S6
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Vero cells were used for propagating and titrating the viruses.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Virus isolates were passaged in Vero E6 cells (ATCC CRL-1586) as previously described (47).
    Vero E6
    suggested: None
    The B16 melanoma mouse model was established by injecting 5×105 B16 cells s.c. 5 days before OV or saline injection into C57BL/6 mice.
    B16
    suggested: None
    The MC38 and ID8 colon adenocarcinoma and ovarian cancer mouse models were established by injecting 5×105 MC38 cells or 1×106 ID8 cells i.p. 4 days before OV or saline injection into C57BL/6 mice.
    MC38
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    In vivo mouse model: Six-to eight-week-old female BALB/c or C57BL/6 mice were purchased from Jackson Laboratories (Bar Harbor, Maine).
    C57BL/6
    suggested: None
    Histopathology: Mice organs including lung, brain, kidney, and liver were freshly isolated from 1×106 pfu OV-spike-, OV-Q1- or saline i.v. injected BALB/c mice on day 70 post injection.
    BALB/c
    suggested: None
    Recombinant DNA
    SentencesResources
    The fusion protein was inserted into pT-oriSIE4/5 following the HSV pIE4/5 promoter to construct pT-oriSIE4/5-spike.
    pT-oriSIE4/5
    suggested: None
    pT-oriSIE4/5-spike
    suggested: None
    Software and Algorithms
    SentencesResources
    Flow cytometry data were acquired on a BD LSRFortessa X-20 (BD) and analyzed by FlowJo software.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analysis: Prism software v.8 (GraphPad, CA, USA) and SAS v.
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    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 found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).


    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.


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