Durable protection against SARS-CoV-2 Omicron induced by an adjuvanted subunit vaccine
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Abstract
Despite the remarkable efficacy of COVID-19 vaccines, waning immunity, and the emergence of SARS-CoV-2 variants such as Omicron represents a major global health challenge. Here we present data from a study in non-human primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine, consisting of RBD (receptor binding domain) on the I53-50 nanoparticle, adjuvanted with AS03, currently in Phase 3 clinical trial ( NCT05007951 ). Vaccination induced robust neutralizing antibody (nAb) titers that were maintained at high levels for at least one year after two doses (Pseudovirus nAb GMT: 2207, Live-virus nAb GMT: 1964) against the ancestral strain, but not against Omicron. However, a booster dose at 6-12 months with RBD-Wu or RBD-β (RBD from the Beta variant) displayed on I53-50 elicited equivalent and remarkably high neutralizing titers against the ancestral as well as the Omicron variant. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Importantly, vaccination resulted in protection against Omicron infection in the lung (no detectable virus in any animal) and profound suppression of viral burden in the nares (median peak viral load of 7567 as opposed to 1.3×10 7 copies in unvaccinated animals) at 6 weeks post final booster. Even at 6 months post vaccination, there was significant protection in the lung (with 7 out of 11 animals showing no viral load, 3 out of 11 animals showing ~20-fold lower viral load than unvaccinated controls) and rapid control of virus in the nares. These results highlight the durable cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine platform.
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SciScore for 10.1101/2022.03.18.484950: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Animal subjects and experimentation: Twenty one male rhesus macaques (Macaca mulatta) of Indian origin, aged 5 – 15 years, including 11 animals from the previous study(Arunachalam et al., 2021) were housed and maintained as per National Institutes of Health (NIH) guidelines at the New Iberia Research Center (NIRC) of the University of Louisiana at Lafayette in accordance with the rules and regulations of the Committee on the Care and Use of Laboratory Animal Resources.
Field Sample Permit: For the challenge, the animals were transferred to the Regional Biosafety Level 3 facility at the Tulane National Primate Research Center, where the study was reviewed and approved by the Tulane …SciScore for 10.1101/2022.03.18.484950: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Animal subjects and experimentation: Twenty one male rhesus macaques (Macaca mulatta) of Indian origin, aged 5 – 15 years, including 11 animals from the previous study(Arunachalam et al., 2021) were housed and maintained as per National Institutes of Health (NIH) guidelines at the New Iberia Research Center (NIRC) of the University of Louisiana at Lafayette in accordance with the rules and regulations of the Committee on the Care and Use of Laboratory Animal Resources.
Field Sample Permit: For the challenge, the animals were transferred to the Regional Biosafety Level 3 facility at the Tulane National Primate Research Center, where the study was reviewed and approved by the Tulane University IACUC (protocol 3930)Sex as a biological variable Animal subjects and experimentation: Twenty one male rhesus macaques (Macaca mulatta) of Indian origin, aged 5 – 15 years, including 11 animals from the previous study(Arunachalam et al., 2021) were housed and maintained as per National Institutes of Health (NIH) guidelines at the New Iberia Research Center (NIRC) of the University of Louisiana at Lafayette in accordance with the rules and regulations of the Committee on the Care and Use of Laboratory Animal Resources. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Cells were incubated with an anti-SARS-CoV spike primary antibody directly conjugated to Alexaflour-647 (CR3022-AF647) for 4 hours at room temperature or overnight at 4° C. anti-SARS-CoV spikesuggested: NoneAntibody half-life calculations: Mixed-effects models implemented in MonolixSuite 2021R1 (Lixoft) were used to estimate the corresponding half-lives of antigen-specific antibodies. antigen-specificsuggested: None741172), CD3 BV650 (BD Biosciences, 563916), CD21 PE-CF594 (BD Biosciences, 563474) and Alexa Fluor 488-labeled Beta spike (antibodies-online, ABIN6963740), CD3suggested: (BD Biosciences Cat# 563916, RRID:AB_2738486)antibodies-online , ABIN6963740suggested: NoneExperimental Models: Cell Lines Sentences Resources To perform neutralization assay, Vero E6-TMPRSS2-T2A-ACE2 cells (BEI Resources, NIAID; NR-54970) were seeded at a density of 1×104 per well in half area 96-well black opaque plates (Greiner Bio-One) and were grown overnight at 37°C in a 5% CO2 atmosphere. Vero E6-TMPRSS2-T2A-ACE2suggested: NoneViruses and cells: VeroE6-TMPRSS2 cells were described previously and cultured in complete DMEM in the presence of Gibco Puromycin 10 mg/ml (#A11138-03). nCoV/USA_WA1/2020 (WA/1) was propagated from an infectious SARS-CoV-2 clone as previously described(Xie et al., 2020). VeroE6-TMPRSS2suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Software and Algorithms Sentences Resources Animal subjects and experimentation: Twenty one male rhesus macaques (Macaca mulatta) of Indian origin, aged 5 – 15 years, including 11 animals from the previous study(Arunachalam et al., 2021) were housed and maintained as per National Institutes of Health (NIH) guidelines at the New Iberia Research Center (NIRC) of the University of Louisiana at Lafayette in accordance with the rules and regulations of the Committee on the Care and Use of Laboratory Animal Resources. NIRCsuggested: NoneThe FRNT-50 titers were interpolated using a 4-parameter nonlinear regression in GraphPad Prism 9.2.0. GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)All flow cytometry data were analysed using Flowjo software v10 (TreeStar Inc.). Flowjosuggested: (FlowJo, RRID:SCR_008520)All the figures were made in GraphPad Prism or R and organized in Adobe Illustrator. Adobe Illustratorsuggested: (Adobe Illustrator, RRID:SCR_010279)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 NCT05007951 Recruiting Immunogenicity and Safety Study of SK SARS-CoV-2 Recombinant… 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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