Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2
Open accessPreprint — published as 10.1126/sciimmunol.abl4509 · Paper page
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 160 million infections and more than 3 million deaths worldwide. While effective vaccines are currently being deployed, the adaptive immune determinants which promote viral clearance and confer protection remain poorly defined. Using mouse models of SARS-CoV-2, we demonstrate that both humoral and cellular adaptive immunity contributes to viral clearance in the setting of primary infection. Furthermore, we find that either convalescent mice, or mice that receive mRNA vaccination are protected from both homologous infection and infection with a variant of concern, B.1.351. Additionally, we find this protection to be largely mediated by antibody response and not cellular immunity. These results highlight the in vivo protective capacity of antibodies generated to both vaccine and natural infection. One-Sentence Summary: Defining the roles of humoral and cellular adaptive immunity in viral clearance and protection from SARS-CoV-2 and a variant of concern.
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Neutralizing antibodies are a likely correlate of protection against SARS-CoV-2 infection.
“Neutralizing antibodies are a likely correlate of protection against SARS-CoV-2 infection, as suggested by vaccine efficacy studies, preclinical studies in mice and non-human primates, and data from the early use of convalescent plasma in elderly patients 4,5,10,13,14,18,23 .”
From Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2 (2021) · cites this paper as [5]
T cells might limit disease progression when neutralizing antibody titres are low.
“Although it is increasingly recognized that neutralizing antibodies dominate protection against initial infection 4,13 , T cells might limit disease progression 5 when neutralizing antibody titres are low 14 .”
From Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2 (2021) · cites this paper as [5]
There is increasing evidence that neutralizing responses are a correlate of protection.
“There is increasing evidence that neutralizing responses are a correlate of protection [4][5][6] .”
From Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2 (2021) · cites this paper as [5]
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Montoya, B., Melo‐Silva, C. R., Tang, L., Kafle, S., Lidskiy, P., Bajusz, C., Vadovics, M., Muramatsu, H., Ábrahám, E., Lipinszki, Z., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.04.019 · Cited by 12 · see citing works
- Authors
- Israelow, B., Mao, T., Klein, J., Song, E., Menasche, B., Omer, S. B., & Iwasaki, A.
- Affiliations
- Yale University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Iwasaki, Akiko
- Venue
- Science Immunology
- Publisher
- openRxiv
- Published
- 2021-05-19
- Volume
- 6
- Issue
- 64
- Pages
- eabl4509-eabl4509
- ISSN
- 2470-9468 (ISSN-L)
- PMC
- PMC9047536
- OpenAlex
- W3197127917
- Cited by
- 189
- References
- 52
- Citations by year
- 2026: 9 · 2025: 23 · 2024: 26 · 2023: 43 · 2022: 67 · 2021: 21
- FWCI
- 13.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Science Immunology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Yale University
- National Institutes of Health (UL1TR001863)
- National Cancer Institute (F30CA239444)
- National Institute of General Medical Sciences (T32GM007205)
- National Institute of Allergy and Infectious Diseases (R01AI157488, K08AI163493, T32AI007019, T32AI007517)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- SARS-CoV-2, adaptive immunity, viral clearance, humoral immunity, cell-mediated immunity, antibody response, mRNA vaccination, B.1.351 variant, Omicron variant, COVID-19 protection, mouse model
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