Protection of human ACE2 transgenic Syrian hamsters from SARS CoV-2 variants by human polyclonal IgG from hyper-immunized transchromosomic bovines
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Abstract
Pandemic SARS CoV-2 has been undergoing rapid evolution during spread throughout the world resulting in the emergence of many Spike protein variants, some of which appear to either evade antibody neutralization, transmit more efficiently, or potentially exhibit increased virulence. This raises significant concerns regarding the long-term efficacy of protection elicited after primary infection and/or from vaccines derived from single virus Spike (S) genotypes, as well as the efficacy of anti-S monoclonal antibody based therapeutics. Here, we used fully human polyclonal human IgG (SAB-185), derived from hyperimmunization of transchromosomic bovines with DNA plasmids encoding the SARS-CoV-2 Wa-1 strain S protein or purified ectodomain of S protein, to examine the neutralizing capacity of SAB-185 in vitro and the protective efficacy of passive SAB-185 antibody (Ab) transfer in vivo . The Ab preparation was tested for neutralization against five variant SARS-CoV-2 strains: Munich (Spike D614G), UK (B.1.1.7), Brazil (P.1) and SA (B.1.3.5) variants, and a variant isolated from a chronically infected immunocompromised patient (Spike Δ144-146). For the in vivo studies, we used a new human ACE2 (hACE2) transgenic Syrian hamster model that exhibits lethality after SARS-Cov-2 challenge and the Munich, UK, SA and Δ144-146 variants. SAB-185 neutralized each of the SARS-CoV-2 strains equivalently on Vero E6 cells, however, a control convalescent human serum sample was less effective at neutralizing the SA variant. In the hamster model, prophylactic SAB-185 treatment protected the hamsters from fatal disease and minimized clinical signs of infection. These results suggest that SAB-185 may be an effective treatment for patients infected with SARS CoV-2 variants.
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SciScore for 10.1101/2021.07.26.453840: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All hamster procedures were in accordance with AAALAC procedures and approved by the University pf Pittsburgh IACUC committee (protocol #IS00017405). Sex as a biological variable Equal numbers of male and female hamsters of 6-8 weeks of age were randomized by animal support staff and housed singly after receipt at the University of Pittsburgh. Randomization Equal numbers of male and female hamsters of 6-8 weeks of age were randomized by animal support staff and housed singly after receipt at the University of Pittsburgh. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources A solution of 0.1% … SciScore for 10.1101/2021.07.26.453840: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: All hamster procedures were in accordance with AAALAC procedures and approved by the University pf Pittsburgh IACUC committee (protocol #IS00017405). Sex as a biological variable Equal numbers of male and female hamsters of 6-8 weeks of age were randomized by animal support staff and housed singly after receipt at the University of Pittsburgh. Randomization Equal numbers of male and female hamsters of 6-8 weeks of age were randomized by animal support staff and housed singly after receipt at the University of Pittsburgh. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources A solution of 0.1% immunodiffusion agarose (MP Bio) in 2X Vero E6 growth medium was then added and plaques were developed at 37°C for 72 hours followed by removal of agarose, staining of cells with crystal violet (Fisher Scientific) and counting of plaques. Vero E6suggested: NoneSoftware and Algorithms Sentences Resources Results were evaluated for statistical significance with GraphPad PRISM software. GraphPad PRISMsuggested: (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: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04518410 Recruiting ACTIV-2: A Study for Outpatients With COVID-19 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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