DNA vaccine protection against SARS-CoV-2 in rhesus macaques
Open accessAbstract
Prototype DNA vaccines for SARS-CoV-2: The development of a vaccine to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent biomedical need. Yu et al. designed a series of prototype DNA vaccines against the SARS-CoV-2 spike protein, which is used by the virus to bind and invade human cells. Analysis of the vaccine candidates in rhesus macaques showed that animals developed protective humoral and cellular immune responses when challenged with the virus. Neutralizing antibody titers were also observed at levels similar to those seen in humans who have recovered from SARS-CoV-2 infection. Science , this issue p. 806
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In rhesus macaques immunized with DNA vaccine candidates, titers between 1:60 and 1:200 correlated with complete protection from disease.
“titers between 1:60 and 1:200 correlated with complete protection from disease.”
From An <i>Alphavirus</i> -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates (2020) · cites this paper as [53]
The Immune correlates of vaccine-induced protection section reports higher neutralizing-antibody titers in completely protected than partially protected vaccinated macaques; it defines complete protection as no detectable sgmRNA after challenge. The paper does not identify titers of 1:60 to 1:200 as a range associated with complete protection. The titers of 74 and 170 reported in Construction and immunogenicity are group medians, not protection thresholds (pages not specified in our copy). (LLM, conf=0.88)
Experimental — accuracy not yet measuredLION/repRNA-CoV2S elicited modest but detectable T cell responses in macaques, consistent with previous studies of SARS-CoV-2 S-targeted DNA and live viral vector vaccines tested in nonhuman primates.
“Our findings demonstrate that LION/repRNA-CoV2S elicited modest but detectable T cell responses in macaques (Fig. 5), an outcome that is consistent with previous studies of SARS-CoV-2 S-targeted DNA and live viral vector vaccines tested in nonhuman primates (53, 58).”
From An <i>Alphavirus</i> -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates (2020) · cites this paper as [53]
Binding and neutralizing antibody titres are important correlates of protection for these SARS-CoV-2 vaccines in non-human primates.
“Consistent with prior observations from our laboratory and others15,16,22, these findings suggest that binding and neutralizing antibody titres are important correlates of protection for these SARS-CoV-2 vaccines in non-human primates.”
From Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine (2022) · cites this paper as [15]
In rhesus macaques given DNA vaccine candidates expressing different forms of the SARS-CoV-2 spike protein, post-vaccination neutralizing antibody titers were correlated with protection against SARS-CoV-2 challenge.
“In rhesus macaques given DNA vaccine candidates expressing different forms of the SARS-CoV-2 spike protein, post-vaccination neutralizing antibody titers were correlated with protection against SARS-CoV-2 challenge.17”
From An mRNA Vaccine against SARS-CoV-2 — Preliminary Report (2020) · cites this paper as [17]
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 [10]
Non-neutralizing antibodies may protect through Fc-mediated functions such as phagocytosis, cellular cytotoxicity, and natural killer cell activation.
“Non-NAbs can also have an important role in protection, however, via Fc-mediated effector functions including antibody-dependent phagocytosis, antibody-dependent cellular cytotoxicity and antibody-dependent natural killer cell activation10,25,31.”
From Immunological mechanisms of vaccine-induced protection against COVID-19 in humans (2021) · cites this paper as [10]
High levels of neutralising antibodies against the SARS-CoV-2 spike protein provide substantial protection against reinfection, as supported by data from common human coronaviruses, non-human primate models, and vaccine studies.
“High concentrations of neutralising antibodies targeting the SARS-CoV-2 spike protein offer considerable protection against SARS-CoV-2 reinfection, supported by data from common human coronaviruses and non-human primate models and vaccine studies.”
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Self-citationCOVID-19 vaccines: The status and perspectives in delivery points of view
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Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality
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Self-citationImmune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates
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Self-citationSARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma
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Prospects for a safe COVID-19 vaccine
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Cross-reactive memory T cells and herd immunity to SARS-CoV-2
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Responses to acute infection with SARS-CoV-2 in the lungs of rhesus macaques, baboons and marmosets
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“As a result, SARS-CoV-2 S is the focus of nucleic acid, vectored, and protein subunit vaccines currently being developed and deployed (Corbett et al., 2020a, 2020b; Jackson et al., 2020; Mercado et al., 2020; Polack et al., 2020; Tostanoski et al., 2020; Yu et al., 2020).”
Self-citationA novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2
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Measuring immunity to SARS-CoV-2 infection: comparing assays and animal models
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Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
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Self-citationSARS-CoV-2 neutralizing antibody responses are more robust in patients with severe disease
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Self-citationCorrelates of protection from SARS-CoV-2 infection
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Approaches and Challenges in SARS-CoV-2 Vaccine Development
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Self-citationRecombinant vaccines for COVID-19
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Warp Speed for Coronavirus Disease 2019 (COVID-19) Vaccines: Why Are Children Stuck in Neutral?
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Discrete SARS-CoV-2 antibody titers track with functional humoral stability
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Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models
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Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques
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Self-citationImmunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates
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Self-citation
- Authors
- Yu, J., Tostanoski, L. H., Peter, L., Mercado, N. B., McMahan, K., Mahrokhian, S. H., Nkolola, J. P., Liu, J., Li, Z., Chandrashekar, A., Martinez, D. R., Loos, C., Atyeo, C., Fischinger, S., Burke, J. S., Slein, M. D., Chen, Y., Zuiani, A., Lelis, F. J. N., Travers, M., Habibi, S., Pessaint, L., Van Ry, A., Blade, K., Brown, R., Cook, A., Finneyfrock, B., Dodson, A., Teow, E., Velasco, J., Zahn, R., Wegmann, F., Bondzie, E. A., Dagotto, G., Gebre, M. S., He, X., Jacob-Dolan, C., Kirilova, M., Kordana, N., Lin, Z., Maxfield, L. F., Nampanya, F., Nityanandam, R., Ventura, J. D., Wan, H., Cai, Y., Chen, B., Schmidt, A. G., Wesemann, D. R., Baric, R. S., Alter, G., Andersen, H., Lewis, M. G., & Barouch, D. H.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- University of North Carolina at Chapel Hill (US)
- Ragon Institute of MGH, MIT and Harvard (US)
- Brigham and Women's Hospital (US)
- Bioqual (US)
- Bioqual, Rockville, MD 20852, USA.
- Janssen (Netherlands) (NL)
- Boston Children's Hospital (US)
- Corresponding author
- Yu, Jingyou
- Tostanoski, Lisa H.
- Peter, Lauren
- Mercado, Noe B.
- McMahan, Katherine
- Mahrokhian, Shant H.
- Nkolola, Joseph P.
- Liu, Jinyan
- Li, Zhenfeng
- Chandrashekar, Abishek
- Barouch, Dan H.
- ORCID
- Yu, Jingyou
- Tostanoski, Lisa H.
- Peter, Lauren
- Mercado, Noe B.
- McMahan, Katherine
- Mahrokhian, Shant H.
- Nkolola, Joseph P.
- Liu, Jinyan
- Li, Zhenfeng
- Chandrashekar, Abishek
- Martinez, David R.
- Loos, Carolin
- Atyeo, Caroline
- Fischinger, Stephanie
- Burke, John S.
- Slein, Matthew D.
- Chen, Yuezhou
- Zuiani, Adam
- Lelis, Felipe J. N.
- Travers, Meghan
- Habibi, Shaghayegh
- Pessaint, Laurent
- Van Ry, Alex
- Blade, Kelvin
- Brown, Renita
- Cook, Anthony
- Finneyfrock, Brad
- Dodson, Alan
- Zahn, Roland
- Wegmann, Frank
- Bondzie, Esther A.
- Dagotto, Gabriel
- Gebre, Makda S.
- He, Xuan
- Jacob-Dolan, Catherine
- Kordana, Nicole
- Lin, Zijin
- Maxfield, Lori F.
- Nampanya, Felix
- Nityanandam, Ramya
- Ventura, John D.
- Wan, Huahua
- Cai, Yongfei
- Chen, Bing
- Schmidt, Aaron G.
- Wesemann, Duane R.
- Baric, Ralph S.
- Alter, Galit
- Andersen, Hanne
- Lewis, Mark G.
- Barouch, Dan H.
- Venue
- Science
- Published
- 2020-08-14
- Volume
- 369
- Issue
- 6505
- Pages
- 806-811
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7243363
- OpenAlex
- W3027204812
- Cited by
- 997
- References
- 29
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 42 · 2023: 68 · 2022: 187 · 2021: 408 · 2020: 254
- FWCI
- 30.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion, cc-by)
- UNC Libraries
- Funders
- National Institutes of Health (OD024917, AI129797, AI124377, AI128751, AI126603, AI007151, AI146779, AI121394, AI139538, 272201700036I-0-759301900131-1, AI100625, AI110700, AI132178, AI149644, AI108197)
- Burroughs Wellcome Fund
- Beth Israel Deaconess Medical Center
- Ragon Institute of MGH, MIT, and Harvard
- Mark and Lisa Schwartz Foundation
- Massachusetts Consortium on Pathogen Readiness
- Janssen Vaccines and Prevention BV
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- DNA vaccine, SARS-CoV-2, COVID-19 vaccines, spike protein, rhesus monkeys, neutralizing antibodies, humoral immune response, cell-mediated immunity, vaccine protection
- MeSH terms
- Immunogenicity, Vaccine, Protein Domains, Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Adjuvants, Immunologic, Animals, Antibodies, Viral, Bronchoalveolar Lavage Fluid, Disease Models, Animal, Female, Humans, Immunity, Cellular, Immunization, Secondary, Immunologic Memory, Macaca mulatta, Male, Nasal Mucosa, Pneumonia, Viral, Vaccination, Viral Vaccines, Coronavirus Infections, Vaccines, DNA, Viral Load, Mutant Proteins, Immunity, Humoral, Antibodies, Neutralizing, Pandemics, Spike Glycoprotein, Coronavirus
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