SARS-CoV-2 infection protects against rechallenge in rhesus macaques
Open accessAbstract
Immunity from reinfection: One of the many open questions about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is whether an individual who has cleared the virus can be infected a second time and get sick. Chandrashekar et al. and Deng et al. generated rhesus macaque models of SARS-CoV-2 infection and tested whether natural SARS-CoV-2 infection could result in immunity to viral rechallenge. They found that animals indeed developed immune responses that protected against a second infection. Although there are differences between SARS-CoV-2 infection in macaques and in humans, these findings have key implications for public health and economic initiatives if validated in human studies. Science , this issue p. 812 , p. 818
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Neutralizing antibody titres elicited by CV2CoV to viral variants exceeded the values previously reported as threshold titres for protection (50-100).
“Although our challenge virus in this study was SARS-CoV-2 WA1/2020, the neutralizing antibody titres elicited by CV2CoV to viral variants exceeded the values we previously reported as threshold titres for protection (50–100)17,19,22.”
From Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine (2022) · cites this paper as [17]
The Virology and immunology section reports neutralizing antibody titres of about 100 in infected rhesus macaques, which were subsequently protected against rechallenge. But the Discussion explicitly says the study could not determine immune correlates of protection; it does not establish 50–100 as a protective threshold. The cited paper also does not report CV2CoV titres against variants, which are results of the citing study rather than a finding attributed to this source. (LLM, conf=0.88)
Experimental — accuracy not yet measuredHumoral and cell-mediated immune responses have been associated with vaccine-induced protection against challenge or subsequent rechallenge after SARS-CoV-2 infection in a rhesus macaque model.
“Humoral and cell-mediated immune responses have been associated with vaccine-induced protection against challenge18 or subsequent rechallenge after SARS-CoV-2 infection in a rhesus macaque model.19”
From An mRNA Vaccine against SARS-CoV-2 — Preliminary Report (2020) · cites this paper as [19]
In macaques, primary SARS-CoV-2 infection protects against subsequent viral challenge for at least 28-35 days, with re-exposure boosting binding and neutralizing antibodies and IFNγ secretion by T cells.
“Initial studies in macaques showed that a primary infection with SARS-CoV-2 protects against subsequent viral challenge for at least 28–35 days, with re-exposure driving memory immune responses that included boosting of binding and neutralizing antibody levels as well as of IFNγ secretion by T cells46,47.”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [47]
In early rhesus macaque vaccine studies, spike-directed neutralizing antibody levels were the strongest correlate of protection.
“In early studies of SARS-CoV-2 vaccine candidates in a rhesus macaque model, the amount of NAbs directed at the S protein, which mediates cellular binding, emerged as the strongest correlate of protection10,30.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [30]
Preexisting immunity to SARS-CoV-2 is associated with protection against reinfection in humans and in nonhuman primates.
“Preexisting immunity to SARS-CoV-2 is associated with protection against reinfection in humans (9–11) and in nonhuman primates (12, 13).”
From mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection (2021) · cites this paper as [12]
In two nonhuman primate studies, animals previously infected with SARS-CoV-2 were protected against high-dose re-challenge one month later, and protection was associated with neutralizing antibodies.
“Animals infected with SARS-CoV-2 were protected from a high dose re-challenge with SARS-CoV-2 1 month later, and protection was associated with neutralizing antibodies”
From Adaptive immunity to SARS-CoV-2 and COVID-19 (2021) · cites this paper as Chandrashekar et al., 2020
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“A very recent study by SARSCoV-2-infected rhesus macaques show SARS-CoV-2 infection protects against rechallenge [134], indicating that immunologic approaches to the prevention and treatment of SARS-CoV-2 infection may be possible [134].”
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“This is consistent with non-human primate (NHP) studies where exposure to the live virus provided protection against reinfection without clinical illness, with corresponding neutralizing antibody responses (138, 139).”
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InfluentialSelf-citationResponses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets
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Self-citationCOVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases
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“Rhesus macaques have also been used in COVID-19 studies [30] where the therapeutic effects of adenovirus-vectored vaccine [31], DNA vaccine candidates expressing S protein [32], and remdesivir treatment [33] were confirmed.”
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“To overcome this limit, antibody titre can be used to predict protection against SARS-CoV-2, as already done for many viruses in humans and for SARS-CoV-2 in animal challenges [3, 4].”
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“Additionally, antibodies induced upon infection have been shown to protect from SARS58 CoV-2 reinfection in animal models (7-9).”
Animal and translational models of SARS-CoV-2 infection and COVID-19
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“Monkeys of the Americas, and some Tarsiers, Lemurs and Lorises, differed at signi fi cant contact residues, and protein modelling predicted these differences should greatly reduce the binding af fi nity of SARS-CoV-2 to ACE2, hence moderating susceptibility to infection.”
- Authors
- Chandrashekar, A., Liu, J., Martinot, A. J., McMahan, K., Mercado, N. B., Peter, L., Tostanoski, L. H., Yu, J., Maliga, Z., Nekorchuk, M., Busman-Sahay, K., Terry, M., Wrijil, L. M., Ducat, S., Martinez, D. R., Atyeo, C., Fischinger, S., Burke, J. S., Slein, M. D., Pessaint, L., Van Ry, A., Greenhouse, J., Taylor, T., Blade, K., Cook, A., Finneyfrock, B., Brown, R., Teow, E., Velasco, J., Zahn, R., Wegmann, F., Abbink, P., Bondzie, E. A., Dagotto, G., Gebre, M. S., He, X., Jacob-Dolan, C., Kordana, N., Li, Z., Lifton, M. A., Mahrokhian, S. H., Maxfield, L. F., Nityanandam, R., Nkolola, J. P., Schmidt, A. G., Miller, A. D., Baric, R. S., Alter, G., Sorger, P. K., Estes, J. D., Andersen, H., Lewis, M. G., & Barouch, D. H.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Tufts University (US)
- Harvard University (US)
- Oregon Health & Science University (US)
- Oregon Health & Sciences University, Beaverton, OR 97006, USA.
- University of North Carolina at Chapel Hill (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Bioqual (US)
- Bioqual, Rockville, MD 20852, USA.
- Janssen (Netherlands) (NL)
- Cornell University (US)
- Corresponding author
- Chandrashekar, Abishek
- Liu, Jinyan
- Martinot, Amanda J.
- McMahan, Katherine
- Mercado, Noe B.
- Peter, Lauren
- Tostanoski, Lisa H.
- Yu, Jingyou
- Barouch, Dan H.
- ORCID
- Chandrashekar, Abishek
- Liu, Jinyan
- Martinot, Amanda J.
- McMahan, Katherine
- Mercado, Noe B.
- Peter, Lauren
- Tostanoski, Lisa H.
- Yu, Jingyou
- Maliga, Zoltan
- Busman-Sahay, Kathleen
- Terry, Margaret
- Wrijil, Linda M.
- Ducat, Sarah
- Martinez, David R.
- Atyeo, Caroline
- Fischinger, Stephanie
- Burke, John S.
- Slein, Matthew D.
- Pessaint, Laurent
- Van Ry, Alex
- Greenhouse, Jack
- Taylor, Tammy
- Blade, Kelvin
- Cook, Anthony
- Finneyfrock, Brad
- Brown, Renita
- Zahn, Roland
- Wegmann, Frank
- Abbink, Peter
- Bondzie, Esther A.
- Dagotto, Gabriel
- Gebre, Makda S.
- He, Xuan
- Jacob-Dolan, Catherine
- Kordana, Nicole
- Li, Zhenfeng
- Lifton, Michelle A.
- Mahrokhian, Shant H.
- Maxfield, Lori F.
- Nityanandam, Ramya
- Nkolola, Joseph P.
- Schmidt, Aaron G.
- Miller, Andrew D.
- Baric, Ralph S.
- Alter, Galit
- Sorger, Peter K.
- Estes, Jacob D.
- Andersen, Hanne
- Lewis, Mark G.
- Barouch, Dan H.
- Venue
- Science
- Published
- 2020-08-14
- Volume
- 369
- Issue
- 6505
- Pages
- 812-817
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7243369
- OpenAlex
- W3026558549
- Cited by
- 816
- References
- 25
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 28 · 2023: 55 · 2022: 153 · 2021: 320 · 2020: 236
- FWCI
- 25.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (OD024917, AI129797, AI124377, AI128751, AI126603, AI135098, AI007151, AI146779, 272201700036I-0-759301900131-1, AI100625, AI110700, AI132178, AI149644, AI108197, CA225088, OD011092, OD025002, AI007387)
- Bill and Melinda Gates Foundation (INV-006131)
- Janssen Research and Development (N/A)
- Beth Israel Deaconess Medical Center (N/A)
- Ragon Institute of MGH, MIT and Harvard (N/A)
- Mark and Lisa Schwartz Foundation (N/A)
- Massachusetts Consortium on Pathogen Readiness (N/A)
- Burroughs Wellcome Fund (N/A)
- Emergent Ventures, Mercatus Center (N/A)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, reinfection, immunoprotection, rhesus monkeys, natural infection, immunity, animal models
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Animals, Antibodies, Viral, Bronchoalveolar Lavage Fluid, Disease Models, Animal, Female, Immunity, Cellular, Immunologic Memory, Lung, Macaca mulatta, Male, Nasal Mucosa, Pneumonia, Viral, Recurrence, Virus Replication, Lung Diseases, Interstitial, Coronavirus Infections, Viral Load, Immunity, Humoral, Antibodies, Neutralizing, Pandemics, Spike Glycoprotein, Coronavirus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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