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Clinical Trial
. 2021 Aug;596(7871):268-272.
doi: 10.1038/s41586-021-03681-2. Epub 2021 Jun 9.

Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans

Galit Alter #  1   2 , Jingyou Yu #  1 , Jinyan Liu #  1 , Abishek Chandrashekar #  1 , Erica N Borducchi #  1 , Lisa H Tostanoski #  1 , Katherine McMahan #  1 , Catherine Jacob-Dolan #  1   3 , David R Martinez  4 , Aiquan Chang  1   3 , Tochi Anioke  1 , Michelle Lifton  1 , Joseph Nkolola  1 , Kathryn E Stephenson  1 , Caroline Atyeo  2   3 , Sally Shin  2 , Paul Fields  5 , Ian Kaplan  5 , Harlan Robins  5 , Fatima Amanat  6 , Florian Krammer  6 , Ralph S Baric  4 , Mathieu Le Gars  7 , Jerald Sadoff  7 , Anne Marit de Groot  7 , Dirk Heerwegh  8 , Frank Struyf  8 , Macaya Douoguih  7 , Johan van Hoof  7 , Hanneke Schuitemaker  7 , Dan H Barouch  9   10   11
Affiliations
Clinical Trial

Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans

Galit Alter et al. Nature. 2021 Aug.

Abstract

The Ad26.COV2.S vaccine1-3 has demonstrated clinical efficacy against symptomatic COVID-19, including against the B.1.351 variant that is partially resistant to neutralizing antibodies1. However, the immunogenicity of this vaccine in humans against SARS-CoV-2 variants of concern remains unclear. Here we report humoral and cellular immune responses from 20 Ad26.COV2.S vaccinated individuals from the COV1001 phase I-IIa clinical trial2 against the original SARS-CoV-2 strain WA1/2020 as well as against the B.1.1.7, CAL.20C, P.1 and B.1.351 variants of concern. Ad26.COV2.S induced median pseudovirus neutralizing antibody titres that were 5.0-fold and 3.3-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020 on day 71 after vaccination. Median binding antibody titres were 2.9-fold and 2.7-fold lower against the B.1.351 and P.1 variants, respectively, as compared with WA1/2020. Antibody-dependent cellular phagocytosis, complement deposition and natural killer cell activation responses were largely preserved against the B.1.351 variant. CD8 and CD4 T cell responses, including central and effector memory responses, were comparable among the WA1/2020, B.1.1.7, B.1.351, P.1 and CAL.20C variants. These data show that neutralizing antibody responses induced by Ad26.COV2.S were reduced against the B.1.351 and P.1 variants, but functional non-neutralizing antibody responses and T cell responses were largely preserved against SARS-CoV-2 variants. These findings have implications for vaccine protection against SARS-CoV-2 variants of concern.

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Conflict of interest statement

D.H.B. is a co-inventor on related vaccine patents. M.L.G., J.S., A.M.G., D.H., F.S., M.D., J.V.H. and H.S. are employees of Janssen Pharmaceuticals and may be co-inventors on related vaccine patents. P.A.F, I.K. and H.R. are employees of Adaptive Biotechnologies. F.K. is a co-inventor on related serologic assay patents, and Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2.

Figures

Fig. 1
Fig. 1. Neutralizing and binding antibody responses to SARS-CoV-2 variants.
a, SARS-CoV-2 psVNA responses against WA1/2020, D614G, B.1.1.7, CAL.20C, P.1 and B.1.351 (a), RBD-specific binding antibodies by ELISA against WA1/2020, B.1.1.7, P.1 and B.1.351 (b) and RBD-specific and spike (S)-specific binding antibodies by ECLA against WA1/2020, B.1.1.7, P.1 and B.1.351 (Meso Scale Discovery panel 7) (c) on days 57 and 71. Red bars reflect median responses. Dotted lines reflect the lower limits of quantification. Filled squares denote placebo–placebo; filled circles denote high dose–placebo; open circles denote high dose–high dose; filled triangles denote low dose–placebo; and open triangles denote low dose–low dose. n = 25 independent samples (5 placebo recipients, 20 Ad26.COV2.S vaccine recipients).
Fig. 2
Fig. 2. Systems serology to SARS-CoV-2 variants.
a, Spike-specific ADCP, ADNP, ADCD and ADNKA responses against WA1/2020 (D614G), B.1.1.7 and B.1.351 on day 71. Red bars reflect median responses. Dotted lines reflect median of placebo recipients. Filled circles denote high dose–placebo; open circles denote high dose–high dose; filled triangles denote low dose–placebo; and open triangles denote low dose–low dose. b, Nightingale plots show the median levels of WA1/2020 (D614G), B.1.1.7, B.1.351 spike-specific isotype (IgM, IgA, IgG1, IgG2 and IgG3) (red) and FcγR2a, FcγR2b and FcγR3a (blue) binding. n = 20 independent samples from Ad26.COV2.S vaccine recipients.
Fig. 3
Fig. 3. Cellular immune responses to SARS-CoV-2 variants.
a, Spike-specific pooled peptide IFNγ ELISPOT responses against WA1/2020, B.1.351, B.1.1.7, P.1 and CAL.20C. n = 25 independent samples (5 placebo recipients, 20 Ad26.COV2.S vaccine recipients). PBMC, peripheral blood mononuclear cells. b, Spike-specific pooled peptide IFNγ CD4+ and CD8+ T cell responses by ICS assays against WA1/2020, B.1.351, B.1.1.7, P.1 and CAL.20C. SFC, spot-forming cells. Responses are shown on days 57 and 85. Red bars reflect median responses. Dotted lines reflect lower limits of quantification. Filled squares denote placebo–placebo; filled circles denote high dose–placebo; open circles denote high dose–high dose; filled triangles denote low dose–placebo; and open triangles denote low dose–low dose. n = 20 independent samples from Ad26.COV2.S vaccine recipients.
Fig. 4
Fig. 4. TCRβ repertoire analysis.
a, Spike and non-spike T cell breadth by TCRβ sequencing on day 63. P values were determined by two-sided Wilcoxon rank-sum tests. Red bars reflect median responses. b, Breadth of spike-specific CD8+ and CD4+ T cell responses. Filled squares denote placebo–placebo; filled circles denote high dose–placebo; open circles denote high dose–high dose; filled triangles denote low dose–placebo; open triangles denote low dose–low dose; and plus signs denote convalescent samples. In the box-and-whisker plots, the middle line reflects the median, the box reflects the 25th–75th percentiles and the whiskers extend the full range up to 1.5× the interquartile range, with outlier points marked individually. n = 32 independent samples (8 SARS-CoV-2 convalescent individuals, 5 placebo recipients, 19 Ad26.COV2.S vaccine recipients).
Extended Data Fig. 1
Extended Data Fig. 1. Live virus neutralizing antibody responses to SARS-CoV-2 variants.
SARS-CoV-2 live virus neutralizing antibody responses against WA1/2020, B.1.1.7 and B.1.351. Red bars reflect median responses. Dotted lines reflect lower limits of quantitation. Filled squares, placebo–placebo; filled circles, high dose–placebo; open circles, high dose–high dose; filled triangles, low dose–placebo; open triangles, low dose–low dose. n = 25 independent samples (5 placebo recipients, 20 Ad26.COV2.S vaccine recipients).
Extended Data Fig. 2
Extended Data Fig. 2. RBD-specific functional antibody responses to SARS-CoV-2 variants.
Top, RBD-specific ADCP, ADNP and ADCD against WA1/2020 (D614G), B.1.1.7 and B.1.351. LD, low dose; HD, high dose; PL, placebo on day 71. Filled circles, high dose–placebo; open circles, high dose–high dose; filled triangles, low dose–placebo; open triangles, low dose–low dose. Bottom, RBD-specific isotype (IgG1, IgG3, IgA, IgM) (red) and FcγR2a, FcγR2b, FcγR3a (blue) binding against WA1/2020 (D614G), B.1.1.7, B.1.351 on day 71. n = 20 independent samples from Ad26.COV2.S vaccine recipients.
Extended Data Fig. 3
Extended Data Fig. 3. Representative gating for ICS assays.
Sample gating plots are shown.
Extended Data Fig. 4
Extended Data Fig. 4. Ratio of variants versus WA1/2020 CD8+ T cell responses.
Ratio of spike-specific pooled peptide IFNγ CD8+ T cell responses by ICS assays against B.1.351, B.1.1.7 and P.1 versus WA1/2020 on days 57 and 85. Red bars reflect median responses. Filled circles, high dose–placebo; open circles, high dose–high dose; filled triangles, low dose–placebo; open triangles, low dose–low dose. n = 20 independent samples from Ad26.COV2.S vaccine recipients.
Extended Data Fig. 5
Extended Data Fig. 5. Central and effector memory CD8+ T cell responses to SARS-CoV-2 variants.
Spike-specific pooled peptide IFNγ central memory CD27+CD45RA− and effector memory CD27−CD45RA− CD8+ T cell responses by ICS assays against WA1/2020, B.1.351, B.1.1.7, P.1 and CAL.20C on days 57 and 85. Red bars reflect median responses. Dotted lines reflect lower limits of quantification. Filled circles, high dose–placebo; open circles, high dose–high dose; filled triangles, low dose–placebo; open triangles, low dose–low dose. n = 20 independent samples from Ad26.COV2.S vaccine recipients.
Extended Data Fig. 6
Extended Data Fig. 6. Central and effector memory CD4+ T cell responses to SARS-CoV-2 variants.
Spike-specific pooled peptide IFNγ central memory CD27+CD45RA− and effector memory CD27−CD45RA− CD4+ T cell responses by ICS assays against WA1/2020, B.1.351, B.1.1.7, P.1 and CAL.20C on days 57 and 85. Red bars reflect median responses. Dotted lines reflect lower limits of quantification. Filled circles, high dose–placebo; open circles, high dose–high dose; filled triangles, low dose–placebo; open triangles, low dose–low dose. n = 20 independent samples from Ad26.COV2.S vaccine recipients.
Extended Data Fig. 7
Extended Data Fig. 7. Polyfunctional CD8+ and CD4+ T cell responses.
WA1/2020 spike-specific pooled peptide monofunctional and multifunctional IFNγ, IL-2 and TNF CD8+ and CD4+ T cell responses by ICS assays on days 57 and 85. Red bars reflect median responses. Dotted lines reflect lower limits of quantification. Filled circles, high dose–placebo; open circles, high dose–high dose; filled triangles, low dose–placebo; open triangles, low dose–low dose. n = 20 independent samples from Ad26.COV2.S vaccine recipients.
Extended Data Fig. 8
Extended Data Fig. 8. CD8+ TCRβ repertoire analysis.
CD8+ T cell breadth and depth by TCRβ sequencing on day 57. Red bars reflect median responses. Filled squares, placebo–placebo; filled circles, high dose–placebo; open circles, high dose–high dose; filled triangles, low dose–placebo; open triangles, low dose–low dose; plus signs, convalescent samples. n = 32 independent samples (8 SARS-CoV-2 convalescent individuals, 5 placebo recipients, 19 Ad26.COV2.S vaccine recipients).
Extended Data Fig. 9
Extended Data Fig. 9. CD4+ TCRβ repertoire analysis.
CD4+ T cell breadth and depth by TCRβ sequencing on day 57. Red bars reflect median responses. Filled squares, placebo–placebo; filled circles, high dose–placebo; open circles, high dose–high dose; filled triangles, low dose–placebo; open triangles, low dose–low dose; plus signs, convalescent samples. n = 32 independent samples (8 SARS-CoV-2 convalescent individuals, 5 placebo recipients, 19 Ad26.COV2.S vaccine recipients).
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References

    1. Sadoff, J. et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N. Engl. J. Med. 10.1056/NEJMoa2101544 (2021). - PMC - PubMed
    1. Stephenson KE, et al. Immunogenicity of the Ad26.COV2.S Vaccine for COVID-19. J. Am. Med. Assoc. 2021;325:1535–1544. doi: 10.1001/jama.2021.3645. - DOI - PMC - PubMed
    1. Mercado NB, et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature. 2020;586:583–588. doi: 10.1038/s41586-020-2607-. - DOI - PMC - PubMed
    1. Wang P, et al. Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature. 2021;593:130–135. doi: 10.1038/s41586-021-03398-2. - DOI - PubMed
    1. Wibmer CK, et al. SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nat. Med. 2021;27:622–625. doi: 10.1038/s41591-021-01285-x. - DOI - PubMed

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