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

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

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.

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. Neutralizing and binding antibody responses… — **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. 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. Cellular immune responses to SARS-CoV-2… — **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. 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. Live virus neutralizing… — **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. RBD-specific functional antibody… — **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. Representative gating for… — **Extended Data Fig. 3. Representative gating for ICS assays.**
Sample gating plots are shown.

Extended Data Fig. 4. Ratio of variants… — **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. Central and effector… — **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. Central and effector… — **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. Polyfunctional CD8 +… — **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. CD8 + TCRβ… — **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. CD4 + TCRβ… — **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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Source: PubMed

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

Abstract

Conflict of interest statement

Figures

References

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