Omicron Booster in Ancestral Strain Vaccinated Mice Augments Protective Immunities Against Both Delta and Omicron Variants

Abstract

A booster vaccination is called for constraining the evolving epidemic of SARS-CoV-2. However, the necessity of a new COVID-19 vaccine is currently unclear. To compare the effect of an Omicron-matched S DNA vaccine and an ancestral S DNA vaccine in boosting cross-reactive immunities, we firstly immunized mice with two-dose of a DNA vaccine encoding the spike protein of the ancestral Wuhan strain. Then the mice were boosted with DNA vaccines encoding spike proteins of either the Wuhan strain or the Omicron variant. Specific antibody and T cell responses were measured at 4 weeks post boost. Our data showed that the Omicron-matched vaccine efficiently boosted RBD binding antibody and neutralizing antibody responses against both the Delta and the Omicron variants. Of note, antibody responses against the Omicron variant elicited by the Omicron-matched vaccine were much stronger than those induced by the ancestral S DNA vaccine. Meanwhile, CD8 ⁺ T cell responses against both the ancestral Wuhan strain and the Omicron strain also tended to be higher in mice boosted by the Omicron-matched vaccine than those in mice boosted with the ancestral S DNA vaccine, albeit no significant difference was observed. Our findings suggest that an Omicron-matched vaccine is preferred for boosting cross-protective immunities.

SciScore for 10.1101/2022.02.19.481110: (What is this?)

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

Table 1: Rigor

Ethics	IRB: Mice experiments were reviewed and approved by the Research Ethics Review Committee of Shanghai Public Health Clinical Center.
Sex as a biological variable	Mouse vaccination: Female C57BL/6J mice, 6-8-week-old, were purchased from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China) and housed in the SPF animal facility of Shanghai Public Health Clinical Center.
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.
Cell Line Authentication	not detected.

Table 2: Resources

Antibodies
Sentences	Resources
Then, 100μl of a HRP labeled goat anti-mouse IgG antibody (Cat# 115-035-003, Jackson Immuno Research, USA) diluted in 1×PBS containing 5% milk were added to each …

SciScore for 10.1101/2022.02.19.481110: (What is this?)

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

Table 1: Rigor

Ethics	IRB: Mice experiments were reviewed and approved by the Research Ethics Review Committee of Shanghai Public Health Clinical Center.
Sex as a biological variable	Mouse vaccination: Female C57BL/6J mice, 6-8-week-old, were purchased from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China) and housed in the SPF animal facility of Shanghai Public Health Clinical Center.
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.
Cell Line Authentication	not detected.

Table 2: Resources

Antibodies
Sentences	Resources
Then, 100μl of a HRP labeled goat anti-mouse IgG antibody (Cat# 115-035-003, Jackson Immuno Research, USA) diluted in 1×PBS containing 5% milk were added to each well and incubated for 1 hour at 37°C.	anti-mouse IgG suggested: (Jackson ImmunoResearch Labs Cat# 115-035-003, RRID:AB_10015289)
Experimental Models: Cell Lines
Sentences	Resources
Next, Vero cells were added into each well (2×104 cells/well) and the plates were incubated at 37°C in a humidified incubator with 5% CO2.	Vero suggested: RRID:CVCL_ZW93)
Experimental Models: Organisms/Strains
Sentences	Resources
Mouse vaccination: Female C57BL/6J mice, 6-8-week-old, were purchased from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China) and housed in the SPF animal facility of Shanghai Public Health Clinical Center.	C57BL/6J suggested: None
Software and Algorithms
Sentences	Resources
PE/Cyanine7-labeled anti-mouse CD3, Cat# 100220, BioLegend;	BioLegend suggested: (BioLegend, RRID:SCR_001134)
The data were analyzed using the FlowJo 10 software (BD Biosciences, USA).	FlowJo suggested: (FlowJo, RRID:SCR_008520)
Statistical analysis: All statistical analyses were performed using GraphPad Prism 8 (GraphPad Software, Inc., La Jolla, CA, USA).	GraphPad Prism suggested: (GraphPad Prism, RRID:SCR_002798) 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: We detected the following sentences addressing limitations in the study:

We note two major limitations in our study. First, we were not able to conduct a live-virus challenge experiment, therefore, we do not know whether the observed improvements of humoral and cellular immunities can be translated into superior protection. Second, the results were generated using a mouse model, which might not completely mimic the characteristics of human immune responses. The Omicron variant challenge studies in animals and vaccination in humans will be required for corroboration.

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.

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

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Omicron Booster in Ancestral Strain Vaccinated Mice Augments Protective Immunities Against Both Delta and Omicron Variants

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