Efficacy of a Broadly Neutralizing SARS-CoV-2 Ferritin Nanoparticle Vaccine in Nonhuman Primates
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Abstract
The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine in nonhuman primates (NHPs). High-dose (50 µ g) SpFN vaccine, given twice within a 28 day interval, induced a Th1-biased CD4 T cell helper response and a peak neutralizing antibody geometric mean titer of 52,773 against wild-type virus, with activity against SARS-CoV-1 and minimal decrement against variants of concern. Vaccinated animals mounted an anamnestic response upon high-dose SARS-CoV-2 respiratory challenge that translated into rapid elimination of replicating virus in their upper and lower airways and lung parenchyma. SpFN’s potent and broad immunogenicity profile and resulting efficacy in NHPs supports its utility as a candidate platform for SARS-like betacoronaviruses.
A SARS-CoV-2 Spike protein ferritin nanoparticle vaccine, co-formulated with a liposomal adjuvant, elicits broad neutralizing antibody responses that exceed those observed for other major vaccines and rapidly protects against respiratory infection and disease in the upper and lower airways and lung tissue of nonhuman primates.
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SciScore for 10.1101/2021.03.24.436523: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable In this study, 32 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 4 cohorts of 8 animals (table S1). Table 2: Resources
Antibodies Sentences Resources We expanded the assessment of the breadth of SpFN immunogenicity by interrogating the neutralizing and non-neutralizing antibody and cellular immune responses against SARS-CoV-1, Binding of vaccinee sera to SARS-CoV-1 RBD, as measured by biolayer interferometry, was absent in controls but was … SciScore for 10.1101/2021.03.24.436523: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable In this study, 32 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 4 cohorts of 8 animals (table S1). Table 2: Resources
Antibodies Sentences Resources We expanded the assessment of the breadth of SpFN immunogenicity by interrogating the neutralizing and non-neutralizing antibody and cellular immune responses against SARS-CoV-1, Binding of vaccinee sera to SARS-CoV-1 RBD, as measured by biolayer interferometry, was absent in controls but was relatively potent in vaccinated animals—binding at half the strength of that observed to SARS-CoV-2 RBD (fig. S3, S4, Fig. 6A). SARS-CoV-1suggested: NoneS3suggested: NoneAntibody-dependent cellular phagocytosis (ADCP) activity also increased remarkably in all vaccine groups, reaching a score that was 100-fold higher two-weeks after last 50 µg SpFN vaccination than baseline or unvaccinated controls (Fig. 6B). Antibody-dependent cellular phagocytosis (ADCPsuggested: NoneSoftware and Algorithms Sentences Resources Animals were vaccinated intramuscularly with either 50 or 5 µg of SpFN, formulated with ALFQ, or 1ml of phosphate buffer solution (PBS) in the anterior proximal quadriceps muscle, on alternating sides with each dose in the series. ALFQsuggested: (aLFQ, RRID:SCR_005925)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: We detected the following sentences addressing limitations in the study:We have made attempts to overcome this limitation by analyzing specimens with orthogonal assays harmonized to consensus platforms. Additionally, our pseudovirus neutralization assay demonstrated equivalence to others in a multi-site concordance survey of reference laboratories. Potent neutralizing antibody responses may offer advantages for both vaccine efficacy and durability. Thus far, neutralizing activity has been predictive of efficacy in human trials, as vaccines that generate lower antibody titers have diminished efficacy (34). An open question remains, however, regarding the length of immunity conferred by SARS-CoV-2 vaccines. For those infectious diseases that are contained by neutralizing antibodies, peak titers have been shown to predict durability (43-45). As such, SpFN may offer longer protection than counterparts; though this requires empirical confirmation. Cross-neutralizing activity against SARS-CoV-2 VOCs is largely diminished for other vaccines at an approximately ten-fold reduction. SpFN induced serum cross-neutralizing responses, however, that were not significantly reduced. Additionally, we found serum binding to mutated SARS-CoV-2 RBD was either unaffected or mildly diminished. Cross-neutralizing activity against SARS-CoV-1 has not been reported yet for other vaccines in advanced development. Some early reports of nanoparticle vaccine approaches presenting RBD have begun to show breadth of neutralizing but these studies either have been limited murine i...
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.
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- No protocol registration statement was detected.
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