SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern
- Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, United States
- HDT Bio, United States
- Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, United States
- Department of Microbiology, University of Washington School of Medicine, United States
- Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, United States
Figures
Figure 1
Design of full-length SARS-CoV2 spike immunogens harboring deletions and/or substitutions specific to variants of concern.
(A) Using the full-length, pre-fusion-stabilized (KV995PP) spike (S) of the original A.1 lineage of SARS-CoV2 as a reference, including the signal peptide (sp) and regions corresponding to S1, S2, …
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Figure 1—source data 1
Source data for Figure 1.
- https://cdn.elifesciences.org/articles/75537/elife-75537-fig1-data1-v2.xlsx
Figure 2
Relative binding and neutralizing antibody responses induced by each vaccine candidate.
C57BL/6 mice (n = 8/group) received a 1 µg intramuscular injection on days 0 and 28 of lipid inorganic nanoparticle (LION)/replicating RNA (repRNA) encoding either the native conformation of spike …
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Figure 2—source data 1
Source data for Figure 2.
- https://cdn.elifesciences.org/articles/75537/elife-75537-fig2-data1-v2.xlsx
Figure 3
Post-boost neutralizing antibody responses in Syrian Golden hamsters.
Sera from animals immunized with lipid inorganic nanoparticle (LION) complexed with replicating RNA (repRNA) vaccine variants A.1, B.1.1.7, or B.1.351 were incubated with live virus of variant A.1 …
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Figure 3—source data 1
Source data for Figure 3.
- https://cdn.elifesciences.org/articles/75537/elife-75537-fig3-data1-v2.xlsx
Figure 4
Replicating RNA (repRNA) vaccination significantly reduces viral shedding.
Mock or repRNA-vaccinated hamsters were challenged with 1000 tissue-culture infectious dose 50 assay (TCID50) of the indicated SARS-CoV2 strains via the IN route. At day 2 or 4 post-infection (PI), …
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Figure 4—source data 1
Source data for Figure 4.
- https://cdn.elifesciences.org/articles/75537/elife-75537-fig4-data1-v2.xlsx
Figure 5
Replicating RNA (repRNA) vaccination significantly reduces viral burden in the lungs.
Mock or repRNA-vaccinated hamsters were challenged with 1000 tissue-culture infectious dose 50 assay (TCID50) of the indicated SARS-CoV2 strains via the IN route. At day 4 post-infection (PI), …
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Figure 5—source data 1
Source data for Figure 5.
- https://cdn.elifesciences.org/articles/75537/elife-75537-fig5-data1-v2.xlsx
Figure 6
Replicating RNA (repRNA) vaccination reduces lung pathology and SARS-CoV2 antigen burden in lung tissue.
Mock or repRNA-vaccinated hamsters were challenged with 1000 tissue-culture infectious dose 50 assay (TCID50) of the indicated SARS-CoV2 strains via the IN route. At day 4 post-infection (PI), …
Figure 7
Replicating RNA (repRNA) vaccination significantly protects against lung pathology in hamsters.
Mock or repRNA-vaccinated hamsters were challenged with 1000 tissue-culture infectious dose 50 assay (TCID50) of the indicated SARS-CoV2 strains via the IN route. At day 4 post-infection (PI), …
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Figure 7—source data 1
Source data for Figure 7.
- https://cdn.elifesciences.org/articles/75537/elife-75537-fig7-data1-v2.xlsx
Tables
Table 1
Fraction of hamster samples with any detectable infectious virus.
| Challenge | RNA | Oral swabs | Lung tissue | |
|---|---|---|---|---|
| D2 | D4 | D4 | ||
| A.1 | Mock | 6/6 | 6/6 | 6/6 |
| A.1 (604) | 6/6 | 2/6 | 1/6 | |
| B.1.351 (671) | 6/6 | 6/6 | 1/6 | |
| B.1.17 (673) | 3/6 | 0/6 | 0/6 | |
| B.1.351 | Mock | 5/5 | 5/5 | 5/5 |
| A.1 (604) | 6/6 | 2/6 | 0/6 | |
| B.1.351 (671) | 2/6 | 2/6 | 0/6 | |
| B.1.17 (673) | 3/6 | 2/6 | 0/6 | |
| B.1.1.7 | Mock | 6/6 | 6/6 | 6/6 |
| A.1 (604) | 6/6 | 2/6 | 0/6 | |
| B.1.351 (671) | 2/6 | 3/6 | 0/6 | |
| B.1.17 (673) | 1/6 | 3/6 | 0/6 | |
Additional files
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Supplementary file 1
Complete histological and immunohistochemistry (IHC) findings.
- https://cdn.elifesciences.org/articles/75537/elife-75537-supp1-v2.xlsx
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Transparent reporting form
- https://cdn.elifesciences.org/articles/75537/elife-75537-transrepform1-v2.docx
