Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques
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Abstract
The emergence of SARS-CoV-2 variants of concern (VOCs) that reduce the efficacy of current COVID-19 vaccines is a major threat to pandemic control. We evaluate a SARS-CoV-2 spike receptor-binding domain ferritin nanoparticle protein vaccine (RFN) in a nonhuman primate challenge model that addresses the need for a next-generation vaccine with increased pan-SARS breadth of coverage. RFN, adjuvanted with a liposomal-QS21 formulation (ALFQ), elicits humoral and cellular immune responses with excellent breadth and potency against SARS-CoV-2 VOCs and SARS-CoV-1, and protects against high-dose respiratory tract challenge with SARS-CoV-2. Our results support consideration of RFN for vaccine development against multiple concerning members of the Sarbecovirus subgenus of Betacoronaviruses .
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SciScore for 10.1101/2021.04.09.439166: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Animal protocols and procedures were reviewed and approved by the Animal Care and Use Committee of both the US Army Medical Research and Development Command (USAMRDC, protocol 11355007.03) Animal Care and Use Review Office as well as the Institutional Animal Care and Use Committee of Bioqual, Inc. (protocol number 20-092), where nonhuman primates were housed for the duration of the study.
IRB: Convalescent Plasma Samples: A panel of 41 human convalescent-phase plasma samples were obtained from BEI Resources Repository (N=30), StemExpress (East Norritin, PA) (N=7) and a Walter Reed Army Institute of Research institutional review board-approved leukapheresis …SciScore for 10.1101/2021.04.09.439166: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Animal protocols and procedures were reviewed and approved by the Animal Care and Use Committee of both the US Army Medical Research and Development Command (USAMRDC, protocol 11355007.03) Animal Care and Use Review Office as well as the Institutional Animal Care and Use Committee of Bioqual, Inc. (protocol number 20-092), where nonhuman primates were housed for the duration of the study.
IRB: Convalescent Plasma Samples: A panel of 41 human convalescent-phase plasma samples were obtained from BEI Resources Repository (N=30), StemExpress (East Norritin, PA) (N=7) and a Walter Reed Army Institute of Research institutional review board-approved leukapheresis protocol (#1386H) (N=4) for which written informed consent was provided by participants.
Consent: Convalescent Plasma Samples: A panel of 41 human convalescent-phase plasma samples were obtained from BEI Resources Repository (N=30), StemExpress (East Norritin, PA) (N=7) and a Walter Reed Army Institute of Research institutional review board-approved leukapheresis protocol (#1386H) (N=4) for which written informed consent was provided by participants.Randomization not detected. Blinding Tissue section slides were evaluated by a board-certified veterinary anatomic pathologist who was blinded to study group allocations. Power Analysis not detected. Sex as a biological variable Vaccine and adjuvant production: Study design and procedures: Twenty-three male and female specific-pathogen-free, research-naïve Chinese-origin rhesus macaques (age 3 - 7 years) were distributed—on the basis of age, weight and sex—into 3 cohorts of 7-8 animals (Table S1). Table 2: Resources
Antibodies Sentences Resources Stimulations consisted of two pools of peptides spanning the Spike protein of SARS-CoV-2 or SARS-CoV-1 (1 µg/mL, JPT, PM-WCPV-S and PM-CVHSA-S respectively) in the presence of Brefeldin A (0.65 µL/mL, GolgiPlugTM, BD Cytofix/Cytoperm Kit, Cat. 555028), co-stimulatory antibodies anti-CD28 (BD Biosciences Cat. SARS-CoV-1 (1suggested: Noneanti-CD28suggested: NoneFollowing stimulation, cells were stained serially with LIVE/DEAD Fixable Blue Dead Cell Stain (ThermoFisher #L23105) and a cocktail of fluorescent-labeled antibodies (BD Biosciences unless otherwise indicated) to cell surface markers CD4-PE-Cy5.5 (S3.5, ThermoFisher #MHCD0418, Lot 2118390 and 2247858), CD8-BV570 (RPA-T8, BioLegend #301038, Lot B281322), CD45RA BUV395 (5H9, #552888, Lot 154382 and 259854), CD28 BUV737 (CD28.2, #612815, Lot 0113886), CCR7-BV650 (GO43H7, # 353234, Lot B297645 and B316676) and HLA-DR-BV480 (G46-6, # 566113, Lot 0055314). CD8-BV570suggested: NoneRPA-T8suggested: (BD Biosciences Cat# 563795, RRID:AB_2722501)CD45RAsuggested: (BD Biosciences Cat# 552888, RRID:AB_394517)CCR7-BV650suggested: NoneB316676suggested: NoneG46-6suggested: (BD Biosciences Cat# 566113, RRID:AB_2739515)Software and Algorithms Sentences Resources Animals were vaccinated intramuscularly with either 50 or 5 μg of RFN, formulated with ALFQ, and control group animals received 1 mL of PBS, in the anterior proximal quadriceps muscle, on alternating sides with each dose in the series. ALFQsuggested: (aLFQ, RRID:SCR_005925)Sample staining was measured on a FACSymphony™ A5 SORP (Becton Dickenson) and data was analyzed using FlowJo v. FlowJosuggested: (FlowJo, RRID:SCR_008520)Display of multicomponent distributions were performed with SPICE v6.0 (NIH, Bethesda, MD). SPICEsuggested: (SPICE, RRID:SCR_016603)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.
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