Single-Shot Ad26 Vaccine Protects Against SARS-CoV-2 in Rhesus Macaques
Open accessAbstract
A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic 1-8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques (Macaca mulatta) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes 9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials.
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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 [16]
Following challenge, anamnestic binding and neutralizing antibody responses were observed in all CVnCoV-vaccinated animals and in a subset of CV2CoV-vaccinated animals.
“Following challenge, we observed anamnestic binding and neutralizing antibody responses in all CVnCoV-vaccinated animals and in a subset of the CV2CoV-vaccinated animals16 (Extended Data Fig. 6).”
From Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine (2022) · cites this paper as [16]
The Methods (Animals and study design) list Ad26 vaccine groups, not CVnCoV or CV2CoV. The Immune Responses in Vaccinated Animals Following Challenge section reports increased neutralizing antibodies in most Ad26-vaccinated animals but no anamnestic neutralizing response in the Ad26-S.PP group. Searches for CVnCoV and CV2CoV found no passage addressing responses in those groups; the Ad26 findings do not establish or contradict the claim about different vaccines. (LLM, conf=0.78)
Experimental — accuracy not yet measuredNon-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 [31]
Antibody-dependent complement deposition and antibody-dependent natural killer cell activation are associated with protection from challenge in animal models.
“Antibody-dependent complement deposition and antibody-dependent natural killer cell activation are associated with protection from challenge in animal models.51”
Neutralizing antibodies dominate protection against initial infection.
“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 [13]
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Vanshylla, K., Di Cristanziano, V., Kleipass, F., Dewald, F., Schommers, P., Gieselmann, L., Gruell, H., Schlotz, M., Ercanoglu, M. S., Stumpf, R., et al. (2021) · Cell Host & Microbe · doi:10.1016/j.chom.2021.04.015 · Cited by 153 · see citing works
Rauch, S., Roth, N., Schwendt, K., Fotin-Mleczek, M., Mueller, S. O., & Petsch, B. (2021) · npj Vaccines · doi:10.1038/s41541-021-00311-w · Cited by 165 · see citing works
Adenovirus vector-based vaccine for infectious diseases
Sakurai, F., Tachibana, M., & Mizuguchi, H. (2022) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2021.100432 · Cited by 148 · see citing works
N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2
McCallum, M., Marco, A. D., Lempp, F., Tortorici, M. A., Pinto, D., Walls, A. C., Beltramello, M., Chen, A., Liu, Z., Zatta, F., et al. (2021) · doi:10.1101/2021.01.14.426475 · Cited by 901 · see citing works
CD8 T cells contribute to vaccine protection against SARS-CoV-2 in macaques
Liu, J., Yu, J., McMahan, K., Jacob-Dolan, C., He, X., Giffin, V., Wu, C., Sciacca, M., Powers, O., Nampanya, F., et al. (2022) · Science Immunology · doi:10.1126/sciimmunol.abq7647 · Cited by 132 · see citing works
Self-citationSpencer, A. J., McKay, P. F., Belij-Rammerstorfer, S., Ulaszewska, M., Bissett, C. D., Hu, K., Samnuan, K., Blakney, A. K., Wright, D., Sharpe, H. R., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23173-1 · Cited by 125 · see citing works
Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine
Gebre, M. S., Rauch, S., Roth, N., Yu, J., Chandrashekar, A., Mercado, N. B., He, X., Liu, J., McMahan, K., Martinot, A., et al. (2022) · Nature · doi:10.1038/s41586-021-04231-6 · Cited by 127 · see citing works
Self-citationApproaches and Challenges in SARS-CoV-2 Vaccine Development
Dagotto, G., Yu, J., & Barouch, D. H. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.08.002 · Cited by 103 · see citing works
Self-citationWarp Speed for Coronavirus Disease 2019 (COVID-19) Vaccines: Why Are Children Stuck in Neutral?
Anderson, E. J., Campbell, J. D., Creech, C. B., Frenck, R., Kamidani, S., Munoz, F. M., Nachman, S., & Spearman, P. (2021) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa1425 · Cited by 89 · see citing works
Discrete SARS-CoV-2 antibody titers track with functional humoral stability
Bartsch, Y. C., Fischinger, S., Siddiqui, S. M., Chen, Z., Yu, J., Gebre, M., Atyeo, C., Gorman, M. J., Zhu, A. L., Kang, J., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21336-8 · Cited by 82 · see citing works
Self-citationImmunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models
Kalnin, K. V., Plitnik, T., Kishko, M., Zhang, J., Zhang, D., Beauvais, A., Anosova, N. G., Tibbitts, T., DiNapoli, J., Ulinski, G., et al. (2021) · npj Vaccines · doi:10.1038/s41541-021-00324-5 · Cited by 82 · see citing works
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Low-dose Ad26.COV2.S protection against SARS-CoV-2 challenge in rhesus macaques
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Self-citationShooting at a Moving Target—Effectiveness and Emerging Challenges for SARS-CoV-2 Vaccine Development
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Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates
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Self-citation
- Authors
- Mercado, N. B., Zahn, R., Wegmann, F., Loos, C., Chandrashekar, A., Yu, J., Liu, J., Peter, L., McMahan, K., Tostanoski, L. H., He, X., Martinez, D. R., Rutten, L., Bos, R., van Manen, D., Vellinga, J., Custers, J., Langedijk, J. P., Kwaks, T., Bakkers, M. J. G., Zuijdgeest, D., Rosendahl Huber, S. K., Atyeo, C., Fischinger, S., Burke, J. S., Feldman, J., Hauser, B. M., Caradonna, T. M., Bondzie, E. A., Dagotto, G., Gebre, M. S., Hoffman, E., Jacob-Dolan, C., Kirilova, M., Li, Z., Lin, Z., Mahrokhian, S. H., Maxfield, L. F., Nampanya, F., Nityanandam, R., Nkolola, J. P., Patel, S., Ventura, J. D., Verrington, K., Wan, H., Pessaint, L., Van Ry, A., Blade, K., Strasbaugh, A., Cabus, M., Brown, R., Cook, A., Zouantchangadou, S., Teow, E., Andersen, H., Lewis, M. G., Cai, Y., Chen, B., Schmidt, A. G., Reeves, R. K., Baric, R. S., Lauffenburger, D. A., Alter, G., Stoffels, P., Mammen, M., Van Hoof, J., Schuitemaker, H., & Barouch, D. H.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Janssen (Netherlands) (NL)
- Ragon Institute of MGH, MIT and Harvard (US)
- University of North Carolina at Chapel Hill (US)
- Harvard University (US)
- Bioqual (US)
- Boston Children's Hospital (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Barouch, Dan H.
- ORCID
- Mercado, Noe B.
- Zahn, Roland
- Wegmann, Frank
- Loos, Carolin
- Chandrashekar, Abishek
- Yu, Jingyou
- Liu, Jinyan
- Peter, Lauren
- McMahan, Katherine
- Tostanoski, Lisa H.
- He, Xuan
- Martinez, David R.
- Rutten, Lucy
- Custers, Jerome
- Langedijk, Johannes P.
- Kwaks, Ted
- Bakkers, Mark J. G.
- Zuijdgeest, David
- Atyeo, Caroline
- Fischinger, Stephanie
- Burke, John S.
- Feldman, Jared
- Hauser, Blake M.
- Caradonna, Timothy M.
- Bondzie, Esther A.
- Dagotto, Gabriel
- Gebre, Makda S.
- Hoffman, Emily
- Jacob-Dolan, Catherine
- Li, Zhenfeng
- Lin, Zijin
- Mahrokhian, Shant H.
- Maxfield, Lori F.
- Nampanya, Felix
- Nityanandam, Ramya
- Nkolola, Joseph P.
- Patel, Shivani
- Ventura, John D.
- Verrington, Kaylee
- Wan, Huahua
- Pessaint, Laurent
- Van Ry, Alex
- Blade, Kelvin
- Strasbaugh, Amanda
- Brown, Renita
- Cook, Anthony
- Andersen, Hanne
- Lewis, Mark G.
- Cai, Yongfei
- Chen, Bing
- Schmidt, Aaron G.
- Reeves, R. Keith
- Baric, Ralph S.
- Lauffenburger, Douglas A.
- Alter, Galit
- Schuitemaker, Hanneke
- Barouch, Dan H.
- Venue
- Nature
- Published
- 2020-07-30
- Volume
- 586
- Issue
- 7830
- Pages
- 583-588
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7581548
- OpenAlex
- W3045734160
- Cited by
- 789
- References
- 33
- Citations by year
- 2026: 8 · 2025: 34 · 2024: 32 · 2023: 65 · 2022: 171 · 2021: 378 · 2020: 99
- FWCI
- 23.78
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-01-19)
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services
- Wellcome Trust
- Ragon Institute of MGH, MIT and Harvard
- Massachusetts Consortium on Pathogen Readiness
- National Institutes of Health (5r01ai132178-05, 1f32ai152296-01a1, R01OD024917, AI 108197, AI100625, 272201700036I-0-759301900131-1, AI100625, AI110700, AI132178, AI149644, AI108197, AI110700, AI149644, AI132178, AI128751)
- Biomedical Advanced Research and Development Authority (HHS0100201700018C)
- National Institute of General Medical Sciences (T32GM008313, T32GM007753)
- National Institute of Allergy and Infectious Diseases (R01AI108197, R01-AI132178, R01AI129797, R01AI147884, UM1AI124377, U01AI149644, UM1AI126603, U19AI100625, R01AI146779, U19AI128751, F32 AI152296, R01AI110700, T32AI007387, T32AI007151)
- 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 › Genetics › Virus-based gene therapy research
- Keywords
- SARS-CoV-2, COVID-19 vaccines, spike protein, rhesus monkeys, neutralizing antibodies, vaccine immunogenicity, vaccine efficacy, non-human primates, intranasal challenge, intratracheal challenge, Ad26.COV2-S
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Animals, Disease Models, Animal, Female, Immunity, Cellular, Macaca mulatta, Male, Pneumonia, Viral, Vaccination, Viral Vaccines, Coronavirus Infections, Viral Load, Immunity, Humoral, Pandemics
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