Protection against SARS-CoV-2 Beta Variant in mRNA-1273 Boosted Nonhuman Primates

Abstract

Neutralizing antibody responses gradually wane after vaccination with mRNA-1273 against several variants of concern (VOC), and additional boost vaccinations may be required to sustain immunity and protection. Here, we evaluated the immune responses in nonhuman primates that received 100 µg of mRNA-1273 vaccine at 0 and 4 weeks and were boosted at week 29 with mRNA-1273 (homologous) or mRNA-1273.β (heterologous), which encompasses the spike sequence of the B.1.351 (beta or β) variant. Reciprocal ID ₅₀ pseudovirus neutralizing antibody geometric mean titers (GMT) against live SARS-CoV-2 D614G and the β variant, were 4700 and 765, respectively, at week 6, the peak of primary response, and 644 and 553, respectively, at a 5-month post-vaccination memory time point. Two weeks following homologous or heterologous boost β-specific reciprocal ID ₅₀ GMT were 5000 and 3000, respectively. At week 38, animals were challenged in the upper and lower airway with the β variant. Two days post-challenge, viral replication was low to undetectable in both BAL and nasal swabs in most of the boosted animals. These data show that boosting with the homologous mRNA-1273 vaccine six months after primary immunization provides up to a 20-fold increase in neutralizing antibody responses across all VOC, which may be required to sustain high-level protection against severe disease, especially for at-risk populations.

One-sentence summary

mRNA-1273 boosted nonhuman primates have increased immune responses and are protected against SARS-CoV-2 beta infection.

SciScore for 10.1101/2021.08.11.456015: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Ethics	IACUC: Rhesus macaque model: Animal experiments were carried out in compliance with all pertinent US National Institutes of Health regulations and approval from the Animal Care and Use Committees of the Vaccine Research Center and Bioqual, Inc. (Rockville, MD).
Sex as a biological variable	not detected.
Randomization	not detected.
Blinding	All samples were blinded and evaluated by a board-certified veterinary pathologist.
Power Analysis	not detected.

Table 2: Resources

Antibodies
Sentences	Resources
Multiplex meso-scale ELISA for serum antibody responses: For 10-plex ELISA, 96-well plates precoated with SARS-CoV-2 S-2P (39) and RBD proteins from multiple variants, SARS-CoV-2 N protein, and Bovine Serum …

SciScore for 10.1101/2021.08.11.456015: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Ethics	IACUC: Rhesus macaque model: Animal experiments were carried out in compliance with all pertinent US National Institutes of Health regulations and approval from the Animal Care and Use Committees of the Vaccine Research Center and Bioqual, Inc. (Rockville, MD).
Sex as a biological variable	not detected.
Randomization	not detected.
Blinding	All samples were blinded and evaluated by a board-certified veterinary pathologist.
Power Analysis	not detected.

Table 2: Resources

Antibodies
Sentences	Resources
Multiplex meso-scale ELISA for serum antibody responses: For 10-plex ELISA, 96-well plates precoated with SARS-CoV-2 S-2P (39) and RBD proteins from multiple variants, SARS-CoV-2 N protein, and Bovine Serum Albumin (BSA) and supplied by the manufacturer [Meso Scale Display (MSD)]	Bovine Serum Albumin ( BSA ) suggested: None
Serum antibody epitope definition: Serum epitope mapping competition assays were performed using a Biacore 8K+ (Cytiva) surface plasmon resonance (SPR) spectrometer.	SPR suggested: None
According to manufacturer’s protocol, anti-histidine IgG1 antibody was immobilized on Series S Sensor Chip CM5 (Cytiva) through primary amine coupling using a His capture kit (Cytiva)	anti-histidine IgG1 suggested: None
The following monoclonal antibodies were used: CD3 APC-Cy7 (clone SP34.2, BD Biosciences), CD4 PE-Cy5.5 (clone S3.5, Invitrogen), CD8 BV570 (clone RPA-T8, Biolegend)	CD4 suggested: (BioLegend Cat# 100541, RRID:AB_10897943) CD8 suggested: None
Software and Algorithms
Sentences	Resources
All calculations are performed within Excel and the GraphPad Prism software, v7.0.	Excel suggested: None
Results are reported as absolute serum epitope reactivity and percent competition and statistical analysis was performed using unpaired, two-tailed t-test (Graphpad Prism v.8).	Graphpad Prism suggested: (GraphPad Prism, RRID:SCR_002798)
Samples were acquired on an BD FACSymphony flow cytometer and analyzed using FlowJo version 9.9.6 (Treestar, Inc., Ashland, OR)	FlowJo suggested: (FlowJo, RRID:SCR_008520)
Analyses were performed in R version 4.0.2 and Prism (GraphPad) versions 8.2 and 9.0.2.	Prism suggested: (PRISM, RRID:SCR_005375) GraphPad suggested: (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: 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.
No funding statement was detected.
No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

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Protection against SARS-CoV-2 Beta Variant in mRNA-1273 Boosted Nonhuman Primates

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