Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain (RBD219-N1) Formulated with Aluminum Hydroxide Induces Protective Immunity and Reduces Immune Enhancement
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Abstract
We developed a severe acute respiratory syndrome (SARS) subunit recombinant protein vaccine candidate based on a high-yielding, yeast-engineered, receptor-binding domain (RBD219-N1) of the SARS beta-coronavirus (SARS-CoV) spike (S) protein. When formulated with Alhydrogel®, RBD219-N1 induced high-level neutralizing antibodies against both pseudotyped virus and a clinical (mouse-adapted) isolate of SARS-CoV. Here, we report that mice immunized with RBD219-N1/Alhydrogel® were fully protected from lethal SARS-CoV challenge (0% mortality), compared to ∼ 30% mortality in mice when immunized with the SARS S protein formulated with Alhydrogel®, and 100% mortality in negative controls. An RBD219-N1 formulation Alhydrogel® was also superior to the S protein, unadjuvanted RBD, and AddaVax (MF59-like adjuvant)-formulated RBD in inducing specific antibodies and preventing cellular infiltrates in the lungs upon SARS-CoV challenge. Specifically, a formulation with a 1:25 ratio of RBD219-N1 to Alhydrogel® provided high neutralizing antibody titers, 100% protection with non-detectable viral loads with minimal or no eosinophilic pulmonary infiltrates. As a result, this vaccine formulation is under consideration for further development against SARS-CoV and potentially other emerging and re-emerging beta-CoVs such as SARS-CoV-2.
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SciScore for 10.1101/2020.05.15.098079: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All of the experiments were performed according to National Institutes of Health and United States Department of Agriculture guidelines using experimental protocols approved by the Office of Research Project Protections, Institutional Animal Care and Use Committee (IACUC) at UTMB. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Animals: Six- to eight-week-old, female Balb/c mice were purchased from Charles River (Wilmington, MA, USA), and housed in an approved biosafety level 3 animal facility at the University of Texas Medical Branch (UTMB) at Galveston, Texas. Cell Line Authentication not detected. Table …
SciScore for 10.1101/2020.05.15.098079: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: All of the experiments were performed according to National Institutes of Health and United States Department of Agriculture guidelines using experimental protocols approved by the Office of Research Project Protections, Institutional Animal Care and Use Committee (IACUC) at UTMB. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Animals: Six- to eight-week-old, female Balb/c mice were purchased from Charles River (Wilmington, MA, USA), and housed in an approved biosafety level 3 animal facility at the University of Texas Medical Branch (UTMB) at Galveston, Texas. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources After blocking and then incubating with serially diluted mouse sera, bound IgG antibody was detected using HRP-conjugated anti-mouse IgG (1:2000), followed by the same protocol as described [18, 19, 24]. anti-mouse IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources The plates were mixed well and cultured at room temperature for 1 h before transferring 100 μl of the immune serum-virus mixtures into designated wells of confluent Vero E6 cells grown in 96-well microtiter plates. Vero E6suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Animals: Six- to eight-week-old, female Balb/c mice were purchased from Charles River (Wilmington, MA, USA), and housed in an approved biosafety level 3 animal facility at the University of Texas Medical Branch (UTMB) at Galveston, Texas. Balb/csuggested: RRID:IMSR_ORNL:BALB/cRl)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.
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