Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine
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Abstract
ABSTRACT BACKGROUND The ongoing coronavirus disease (COVID)-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be controlled by an efficacious vaccine. Multiple vaccines are in development, but no efficacious vaccine is currently available. METHODS We designed a multi-center phase 1/2a randomized, double-blinded, placebo-controlled clinical study to assesses the safety, reactogenicity and immunogenicity of Ad26.COV2.S, a non-replicating adenovirus 26 based vector expressing the stabilized pre-fusion spike (S) protein of SARS-CoV-2. Ad26.COV2.S was administered at a dose level of 5×10 10 or 1×10 11 viral particles (vp) per vaccination, either as a single dose or as a two-dose schedule spaced by 56 days in healthy adults (18-55 years old; cohort 1a & 1b; n= 402 and healthy elderly ≥65 years old; cohort 3; n=394). Vaccine elicited S specific antibody levels were measured by ELISA and neutralizing titers were measured in a wild-type virus neutralization assay (wtVNA). CD4+ T-helper (Th)1 and Th2, and CD8+ immune responses were assessed by intracellular cytokine staining (ICS). RESULTS We here report interim analyses after the first dose of blinded safety data from cohorts 1a, 1b and 3 and group unblinded immunogenicity data from cohort 1a and 3. In cohorts 1 and 3 solicited local adverse events were observed in 58% and 27% of participants, respectively. Solicited systemic adverse events were reported in 64% and 36% of participants, respectively. Fevers occurred in both cohorts 1 and 3 in 19% (5% grade 3) and 4% (0% grade 3), respectively, were mostly mild or moderate, and resolved within 1 to 2 days after vaccination. The most frequent local adverse event (AE) was injection site pain and the most frequent solicited AEs were fatigue, headache and myalgia. After only a single dose, seroconversion rate in wtVNA (50% inhibitory concentration - IC50) at day 29 after immunization in cohort 1a already reached 92% with GMTs of 214 (95% CI: 177; 259) and 92% with GMTs of 243 (95% CI: 200; 295) for the 5×10 10 and 1×10 11 vp dose levels, respectively. A similar immunogenicity profile was observed in the first 15 participants in cohort 3, where 100% seroconversion (6/6) (GMTs of 196 [95%CI: 69; 560]) and 83% seroconversion (5/6) (GMTs of 127 [95% CI: <58; 327]) were observed for the 5×10 10 or 1×10 11 vp dose level, respectively. Seroconversion for S antibodies as measured by ELISA (ELISA Units/mL) was observed in 99% of cohort 1a participants (GMTs of 528 [95% CI: 442; 630) and 695 (95% CI: 596; 810]), for the 5×10 10 or 1×10 11 vp dose level, respectively, and in 100% (6/6 for both dose levels) of cohort 3 with GMTs of 507 (95% CI: 181; 1418) and 248 (95% CI: 122; 506), respectively. On day 14 post immunization, Th1 cytokine producing S-specific CD4+ T cell responses were measured in 80% and 83% of a subset of participants in cohort 1a and 3, respectively, with no or very low Th2 responses, indicative of a Th1-skewed phenotype in both cohorts. CD8+ T cell responses were also robust in both cohort 1a and 3, for both dose levels. CONCLUSIONS The safety profile and immunogenicity after only a single dose are supportive for further clinical development of Ad26.COV2.S at a dose level of 5×10 10 vp, as a potentially protective vaccine against COVID-19. Trial registration number NCT04436276
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Licensed SARS-CoV-2 vaccines have shown up to 95% efficacy against laboratory-confirmed infection during the first months after vaccination.
“Currently licensed vaccines have shown efficacies of up to 95% in preventing laboratory-confirmed infection over the first few months after vaccination61–63”
From Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection (2021) · cites this paper as [63]
Robust CD4+ and CD8+ T cell memory is induced after COVID-19, and multiple COVID-19 vaccines elicit CD4+ and CD8+ T cell responses.
“Robust CD4+ and CD8+ T cell memory is induced after COVID-19,22,39, 40, 41 and multiple COVID-19 vaccines elicit CD4+ and CD8+ T cell responses.26,42, 43, 44, 45”
From Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals (2021) · cites this paper as [43]
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- Authors
- Sadoff, J., Le Gars, M., Shukarev, G., Heerwegh, D., Truyers, C., de Groot, A. M., Stoop, J., Tete, S., Van Damme, W., Leroux-Roels, I., Berghmans, P.-J., Kimmel, M., Van Damme, P., de Hoon, J., Smith, W., Stephenson, K. E., De Rosa, S. C., Cohen, K. W., McElrath, M. J., Cormier, E., Scheper, G., Barouch, D. H., Hendriks, J., Struyf, F., Douoguih, M., Van Hoof, J., & Schuitemaker, H.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- From Janssen Vaccines and Prevention, Leiden, the Netherlands (J. Sadoff, M.L.G., G. Shukarev, A.M.G., J. Stoop, S.T., E.C., G. Scheper, J. Hendriks, M.D., J.V.H., H.S.); Janssen Research and Development, Beerse (D.H., C.T., F.S.), Janssen Clinical Pharmacology Unit, Merksem (W.V.D.), the Center for Vaccinology, Ghent University, Gent (I.L.-R.), SGS Life Sciences (P.-J.B.) and the Center for the Evaluation of Vaccination, University of Antwerp (P.V.D.), Antwerp, and the Center for Clinical Pharmacology, University Hospitals Leuven, Leuven (J. de Hoon) — all in Belgium; Optimal Research, Melbourne, FL (M.K.); the Alliance for Multispecialty Research, Knoxville, TN (W.S.); the Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston (K.E.S., D.H.B.); and the Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle (S.C.D.R., K.W.C., M.J.M.).
- Corresponding author
- Schuitemaker, Hanneke
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2021-05-13
- Volume
- 384
- Issue
- 19
- Pages
- 1824-1835
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC7821985
- OpenAlex
- W3119345685
- Cited by
- 1,208
- References
- 15
- Citations by year
- 2026: 19 · 2025: 59 · 2024: 52 · 2023: 142 · 2022: 346 · 2021: 553 · 2020: 36
- FWCI
- 86.62
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Biomedical Advanced Research and Development Authority of the Department of Health and Human Services (HHS0100201700018C)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- COVID-19 vaccines, SARS-CoV-2 spike protein, adenovirus vector vaccine, vaccine safety, reactogenicity, neutralizing antibodies, T cell response, CD4+ T cells, CD8+ T cells, vaccine dose comparison, immunogenicity, fatigue, headache
- MeSH terms
- Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines, Ad26COVS1, Adolescent, Adult, Antibodies, Viral, Double-Blind Method, Humans, Male, Middle Aged, Cohort Studies, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, CD4 Lymphocyte Count, Young Adult, Antibodies, Neutralizing
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