mRNA vaccines induce rapid antibody responses in mice
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Abstract
mRNA vaccines can be developed and produced quickly, making them prime candidates for immediate outbreak responses. Furthermore, clinical trials have demonstrated rapid protection following mRNA vaccination. Thus, we sought to investigate how quickly mRNA vaccines elicit antibody responses compared to other vaccine modalities. We first compared the immune kinetics of mRNA and DNA vaccines expressing SARS-CoV-2 spike in mice. We observed rapid induction of antigen-specific binding and neutralizing antibodies by day 5 following mRNA (4 µg/mouse), but not DNA (50 µg/mouse), immunization. Comparing innate responses hours post immunization, the mRNA vaccine induced increased levels of IL-5, IL-6, and MCP-1 cytokines which maybe promoting humoral responses downstream. We then evaluated the immune kinetics of an HIV-1 mRNA vaccine in comparison to DNA, protein, and rhesus adenovirus 52 (RhAd52) vaccines of the same HIV-1 envelope antigen in mice. Again, induction of envelope-specific antibodies was observed by day 5 following mRNA vaccination, whereas antibodies were detected by day 7–14 following DNA, protein, and RhAd52 vaccination. Thus, eliciting rapid humoral immunity may be a unique and advantageous property of mRNA vaccines for controlling infectious disease outbreaks.
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SciScore for 10.1101/2021.11.01.466863: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All animal experiments adhered to the Beth Israel Deaconess Medical Center Institutional Animal Care and Use Committee guidelines. Sex as a biological variable Mice and study designs: 7-to 8-week-old female C57BL/6 mice (n=5) were purchased from The Jackson Laboratory (Bar Harbor, ME). Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources ELISA: SARS-CoV-2 Spike as well as HIV-1 Env specific binding antibodies were assessed by Enzyme-linked immunosorbent assays (ELISAs) as described previously [13, 14]. 96-well plates were coated with 1 µg/ml of SARS-CoV-2 S protein (Sino Biological) or … SciScore for 10.1101/2021.11.01.466863: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All animal experiments adhered to the Beth Israel Deaconess Medical Center Institutional Animal Care and Use Committee guidelines. Sex as a biological variable Mice and study designs: 7-to 8-week-old female C57BL/6 mice (n=5) were purchased from The Jackson Laboratory (Bar Harbor, ME). Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources ELISA: SARS-CoV-2 Spike as well as HIV-1 Env specific binding antibodies were assessed by Enzyme-linked immunosorbent assays (ELISAs) as described previously [13, 14]. 96-well plates were coated with 1 µg/ml of SARS-CoV-2 S protein (Sino Biological) or HIV-1 clade C Env 459C gp140 in 1× Dulbecco’s phosphate-buffered saline (DPBS) and incubated at 4 °C overnight. HIV-1 clade Csuggested: NoneExperimental Models: Cell Lines Sentences Resources luciferase reporter plasmid pLenti-CMV Puro-Luc (Addgene) and S protein expressing pcDNA3.1-SARS CoV-2 SΔCT were co-transfected into HEK293T cells by lipofectamine 2000 (Thermo Fisher Scientific). HEK293Tsuggested: NoneThe mixture was incubated at 37 °C for 1 h before adding to HEK293T-hACE2 cells. HEK293T-hACE2suggested: RRID:CVCL_A7UK)Experimental Models: Organisms/Strains Sentences Resources Mice and study designs: 7-to 8-week-old female C57BL/6 mice (n=5) were purchased from The Jackson Laboratory (Bar Harbor, ME). C57BL/6suggested: NoneRecombinant DNA Sentences Resources Briefly, the packaging construct psPAX2 (AIDS Resource and Reagent Program) psPAX2suggested: RRID:Addgene_12260)luciferase reporter plasmid pLenti-CMV Puro-Luc (Addgene) and S protein expressing pcDNA3.1-SARS CoV-2 SΔCT were co-transfected into HEK293T cells by lipofectamine 2000 (Thermo Fisher Scientific). pLenti-CMV Puro-Lucsuggested: NonepcDNA3.1-SARSsuggested: NoneSoftware and Algorithms Sentences Resources Briefly, the packaging construct psPAX2 (AIDS Resource and Reagent Program) AIDS Resource and Reagent Programsuggested: NoneStatistical analyses: Statistical analyses were performed using GraphPad Prism (version 9.0) software (GraphPad Software) and comparison between groups was performed using a two-tailed nonparametric Mann-Whitney U t test. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (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 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.
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