Durable antibody responses elicited by 1 dose of Ad26.COV2.S and substantial increase after boosting: 2 randomized clinical trials
Jerald Sadoff, Mathieu Le Gars, Boerries Brandenburg, Vicky Cárdenas, Georgi Shukarev, Nathalie Vaissiere, Dirk Heerwegh, Carla Truyers, Anne Marit de Groot, Mandy Jongeneelen, Krisztian Kaszas, Jeroen Tolboom, Gert Scheper, Jenny Hendriks, Javier Ruiz-Guiñazú, Frank Struyf, Johan Van Hoof, Macaya Douoguih, Hanneke Schuitemaker, Jerald Sadoff, Mathieu Le Gars, Boerries Brandenburg, Vicky Cárdenas, Georgi Shukarev, Nathalie Vaissiere, Dirk Heerwegh, Carla Truyers, Anne Marit de Groot, Mandy Jongeneelen, Krisztian Kaszas, Jeroen Tolboom, Gert Scheper, Jenny Hendriks, Javier Ruiz-Guiñazú, Frank Struyf, Johan Van Hoof, Macaya Douoguih, Hanneke Schuitemaker
Abstract
Background: Ad26.COV2.S is a well-tolerated and effective vaccine against COVID-19. We evaluated durability of anti-SARS-CoV-2 antibodies elicited by single-dose Ad26.COV2.S and the impact of boosting.
Methods: In randomized, double-blind, placebo-controlled, phase 1/2a and phase 2 trials, participants received single-dose Ad26.COV2.S (5 × 1010 viral particles [vp]) followed by booster doses of 5 × 1010 vp or 1.25 × 1010 vp. Neutralizing antibody levels were determined by a virus neutralization assay (VNA) approximately 8-9 months after dose 1. Binding and neutralizing antibody levels were evaluated by an enzyme-linked immunosorbent assay and pseudotyped VNA 6 months after dose 1 and 7 and 28 days after boosting.
Results: Data were analyzed from phase 1/2a participants enrolled from 22 July-18 December 2020 (Cohort 1a, 18-55 years [y], N = 25; Cohort 2a, 18-55y, N = 17; Cohort 3, ≥65y, N = 22), and phase 2 participants from 14 to 22 September 2020 (18-55y and ≥ 65y, N = 73). Single-dose Ad26.COV2.S elicited stable neutralizing antibodies for at least 8-9 months and stable binding antibodies for at least 6 months, irrespective of age. A 5 × 1010 vp 2-month booster dose increased binding antibodies by 4.9- to 6.2-fold 14 days post-boost versus 28 days after initial immunization. A 6-month booster elicited a steep and robust 9-fold increase in binding antibody levels 7 days post-boost. A 5.0-fold increase in neutralizing antibodies was observed by 28 days post-boost for the Beta variant. A 1.25 × 1010 vp 6-month booster elicited a 3.6-fold increase in binding antibody levels at 7 days post-boost versus pre-boost, with a similar magnitude of post-boost responses in both age groups.
Conclusions: Single-dose Ad26.COV2.S elicited durable antibody responses for at least 8 months and elicited immune memory. Booster-elicited binding and neutralizing antibody responses were rapid and robust, even with a quarter vaccine dose, and stronger with a longer interval since primary vaccination.
Trial registration: ClinicalTrials.gov Identifier: NCT04436276, NCT04535453.
Keywords: Ad26.COV2.S; Antibody; COVID-19; Enzyme-linked immunosorbent assay; Vaccine; Virus neutralization assay.
Conflict of interest statement
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors are employees of Janssen Pharmaceuticals, a Johnson & Johnson company, and may hold shares in Johnson & Johnson.
Copyright © 2022. Published by Elsevier Ltd.
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References
- Bos R., Rutten L., van der Lubbe J.E.M., Bakkers M.J.G., Hardenberg G., Wegmann F., et al. Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 spike immunogen induces potent humoral and cellular immune responses. NPJ Vaccines. 2020;5(1) doi: 10.1038/s41541-020-00243-x.
- Our World in Data. Statistics and research: coronavirus (COVID-19) vaccinations, ; [accessed 30 November 2021].
- FDA Briefing Document: Janssen Ad26.COV2.S Vaccine for the Prevention of COVID-19. Vaccines and Related Biological Products Advisory Committee. . [Accessed 27 October 2021].
- Sadoff J., Gray G., Vandebosch A., Cárdenas V., Shukarev G., Grinsztejn B., et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med. 2021;384(23):2187–2201.
- Barouch D.H., Stephenson K.E., Sadoff J., Yu J., Chang A., Gebre M., et al. Durable humoral and cellular immune responses 8 months after Ad26.COV2.S vaccination. N Engl J Med. 2021;385(10):951–953.
- Jongeneelen M., Kaszas K., Veldman D., Huizingh J., van der Vlugt R., Schouten T., et al. Ad26.COV2.S elicited neutralizing activity against Delta and other SARS-CoV-2 variants of concern. bioRxiv. 2021 doi: 10.1101/2021.07.01.450707. Preprint.
- Pfizer-BioNTech. Fact sheet for healthcare providers administering vaccine (vaccination providers). Emergency use authorization (EUA) of the Pfizer-Biontech COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19), ; 2021 [accessed 27 October 2021].
- Moderna. Fact sheet for healthcare providers administering vaccine (vaccination providers). Emergency use authorization (EUA) of the Moderna COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19), ; 2021 [accessed 27 October 2021].
- Sadoff J., Le Gars M., Cardenas V., Shukarev G., Vaissiere N., Heerwegh D., et al. Durability of antibody responses elicited by a single dose of Ad26.COV2.S and substantial increase following late boosting. medRxiv. 2021 doi: 10.1101/2021.08.25.21262569. Preprint.
- Solforosi L., Kuipers H., Jongeneelen M., Rosendahl Huber S.K., van der Lubbe J.E.M., Dekking L., et al. Immunogenicity and efficacy of one and two doses of Ad26.COV2.S COVID vaccine in adult and aged NHP. J Exp Med. 2021;218(7):e20202756. doi: 10.1084/jem.20202756.
- Juraszek J., Rutten L., Blokland S., Bouchier P., Voorzaat R., Ritschel T., et al. Stabilizing the closed SARS-CoV-2 spike trimer. Nat Commun. 2021;12(1) doi: 10.1038/s41467-020-20321-x.
- Sadoff J., Le Gars M., Shukarev G., Heerwegh D., Truyers C., de Groot A.M., et al. Interim results of a phase 1–2a trial of Ad26.COV2.S Covid-19 vaccine. N Engl J Med. 2021;384(19):1824–1835.
- Grannis S.J., Rowley E.A., Ong T.C., Stenehjem E., Klein N.P., DeSilva M.B., et al. Interim estimates of COVID-19 vaccine effectiveness against COVID-19–associated emergency department or urgent care clinic encounters and hospitalizations among adults during SARS-CoV-2 B.1.617.2 (Delta) variant predominance — nine states, June–August 2021. MMWR Morb Mortal Wkly Rep. 2021;70(37):1291–1293.
- Polinski J.M., Weckstein A.R., Batech M., Kabelac C., Kamath T., Harvey R., et al. Effectiveness of the single-dose Ad26.COV2.S COVID vaccine. medRxiv. 2021 doi: 10.1101/2021.09.10.21263385. Preprint.
- Bekker L.G., Garrett N., Goga A., Fairall L., Reddy T., Yende-Zuma N., et al. Effectiveness of the Ad26.COV2.S vaccine in health-care workers in South Africa (the Sisonke study): results from a single-arm, open-label, phase 3B, implementation study. Lancet. 2022;399:1141–1153.
- de Gier B., Kooijman M., Kemmeren J., de Keizer N., Dongelmans D., van Iersel S.C.J.L., et al. COVID-19 vaccine effectiveness against hospitalizations and ICU admissions in the Netherlands, April-August 2021. medRxiv. 2021 doi: 10.1101/2021.09.15.21263613. Preprint.
- Rosenberg E.S., Dorabawila V., Easton D., Bauer U.E., Kumar J., Hoen R., et al. Covid-19 vaccine effectiveness in New York State. N Engl J Med. 2022;386(2):116–127.
- Khoury D.S., Cromer D., Reynaldi A., Schlub T.E., Wheatley A.K., Juno J.A., et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021;27(7):1205–1211.
- Earle K.A., Ambrosino D.M., Fiore-Gartland A., Goldblatt D., Gilbert P.B., Siber G.R., et al. Evidence for antibody as a protective correlate for COVID-19 vaccines. Vaccine. 2021;39(32):4423–4428.
- Gilbert P.B., Montefiori D.C., McDermott A., Fong Y., Benkeser D.C., Deng W., et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy trial. medRxiv. 2021 doi: 10.1101/2021.08.09.21261290. Preprint.
- Moderna. Fact sheet for healthcare providers administering vaccine (vaccination providers): emergency use authorization (EUA) of the Moderna COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19). ; [accessed 31 January 2022]
- Alter G., Yu J., Liu J., Chandrashekar A., Borducchi E.N., Tostanoski L.H., et al. Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans. Nature. 2021;596(7871):268–272.
- Pegu A., O’Connell S.E., Schmidt S.D., O’Dell S., Talana C.A., Lai L., et al. Durability of mRNA-1273 vaccine–induced antibodies against SARS-CoV-2 variants. Science. 2021;373(6561):1372–1377.
- Widge A.T., Rouphael N.G., Jackson L.A., Anderson E.J., Roberts P.C., Makhene M., et al. Durability of responses after SARS-CoV-2 mRNA-1273 vaccination. N Engl J Med. 2021;384(1):80–82.
- Collier A.-RY., Yu J., McMahan K., Liu J., Chandrashekar A., Maron J.S., et al. Differential kinetics of immune responses elicited by Covid-19 vaccines. N Engl J Med. 2021;385(21):2010–2012.
- Pfizer. BNT162b2 [Comirnaty (COVID-19 vaccine, mRNA)]: evaluation of a booster dose (third dose). Vaccines and related biological products advisory committee briefing document 2021. ; [accessed 27 October 2021]
- Stephenson K.E., Wegmann F., Tomaka F., Walsh S.R., Tan C.S., Lavreys L., et al. Comparison of shortened mosaic HIV-1 vaccine schedules: a randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HPX1002) and a preclinical study in rhesus monkeys (NHP 17–22) Lancet HIV. 2020;7(6):e410–e421.
- Salisch N.C., Stephenson K.E., Williams K., Cox F., van der Fits L., Heerwegh D., et al. A double-blind, randomized, placebo-controlled phase 1 study of Ad26.ZIKV.001, an Ad26-vectored anti–Zika virus vaccine. Ann Intern Med. 2021;174(5):585–594.
- Iketani S., Liu L., Nair M.S., Mohri H., Wang M., Huang Y., et al. A third COVID-19 vaccine shot markedly boosts neutralizing antibody potency and breadth. medRxiv. 2021 doi: 10.1101/2021.08.11.21261670. Preprint.
- Atmar R.L., Lyke K.E., Deming M.E., Jackson L.A., Branche A.R., El Sahly H.M., et al. Heterologous SARS-CoV-2 booster vaccinations – preliminary report. medRxiv. 2021 doi: 10.1101/2021.10.10.21264827. Preprint.
- Pollard A.J., Launay O., Lelievre J.-D., Lacabaratz C., Grande S., Goldstein N., et al. Safety and immunogenicity of a two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Europe (EBOVAC2): a randomised, observer-blind, participant-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2021;21(4):493–506.
- See I., Su J.R., Lale A., Woo E.J., Guh A.Y., Shimabukuro T.T., et al. US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021. JAMA. 2021;325(24):2448–2456.
- Shay D.K., Gee J., Su J.R., Myers T.R., Marquez P., Liu R., et al. Safety monitoring of the Janssen (Johnson & Johnson) COVID-19 vaccine — United States, March–April 2021. MMWR Morb Mortal Wkly Rep. 2021;70:680–684. doi: 10.15585/mmwr.mm7018e2.
- Bhuyan P., Medin J., da Silva H.G., Yadavalli M., Shankar N.K., Mullerova H., et al. Very rare thrombosis with thrombocytopenia after second AZD1222 dose: a global safety database analysis. Lancet. 2021;398(10300):577–578.
- Mbaeyi S., Oliver S.E., Collins J.P., Godfrey M., Goswami N.D., Hadler S.C., et al. The Advisory Committee on Immunization Practices’ interim recommendations for additional primary and booster doses of COVID-19 vaccines — United States, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(44):1545–1552.
- US Food and Drug Administration. Fact sheet for healthcare providers administering vaccine (vaccination providers): emergency use authorization (EUA) of the Janssen COVID-19 vaccine to prevent coronavirus disease 2019 (COVID-19), ; 2021 [accessed 20 September 2021].
Source: PubMed