Durable Humoral and Cellular Immune Responses 8 Months after Ad26.COV2.S Vaccination

Barouch, Dan H.; Stephenson, Kathryn E.; Sadoff, Jerald C.; Yu, Jingyou; Chang, Aiquan; Gebre, Makda S.; McMahan, Katherine; Liu, Jinyan; Chandrashekar, Abishek; Patel, Shivani; Gars, Mathieu Le; Groot, Anne Marit de; Heerwegh, Dirk; Struyf, Frank; Douoguih, Macaya; Hoof, Johan Van; Schuitemaker, Hanneke

doi:10.1056/nejmc2108829

Cited by 211 publications

(228 citation statements)

References 5 publications

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“…Reports of neutralizing antibody levels in vaccinated individuals [7,[35][36][37][38] and their effectiveness against various variants are emerging [39]. Recent data [35] suggests that there might be a time-dependent improvement in the neutralizing efficacy of antibodies against variants, which might be due to the expansion and evolution of antibodies in the germinal centers. However, most of the vaccines seem to elicit lower neutralizing antibody titers against the B.1.351 SA variant (beta variant).…”

Section: Discussionmentioning

confidence: 99%

“…In the literature, PBNA has been shown to correlate well with other assays measuring the neutralization antibodies, including the plaque reduction neutralization test [ 33 ], the microneutralization assay, and the ELISA assay [ 34 ]. Reports of neutralizing antibody levels in vaccinated individuals [ 7 , 35 , 36 , 37 , 38 ] and their effectiveness against various variants are emerging [ 39 ]. Recent data [ 35 ] suggests that there might be a time-dependent improvement in the neutralizing efficacy of antibodies against variants, which might be due to the expansion and evolution of antibodies in the germinal centers.…”

Section: Discussionmentioning

confidence: 99%

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SARS-CoV-2 Spike Pseudoviruses: A Useful Tool to Study Virus Entry and Address Emerging Neutralization Escape Phenotypes

et al. 2021

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SARS-CoV-2 genetic variants are emerging around the globe. Unfortunately, several SARS-CoV-2 variants, especially variants of concern (VOCs), are less susceptible to neutralization by the convalescent and post-vaccination sera, raising concerns of increased disease transmissibility and severity. Recent data suggests that SARS-CoV-2 neutralizing antibody levels are a reliable correlate of vaccine-mediated protection. However, currently used BSL3-based virus micro-neutralization (MN) assays are more laborious, time-consuming, and expensive, underscoring the need for BSL2-based, cost-effective neutralization assays against SARS-CoV-2 variants. In light of this unmet need, we have developed a BSL-2 pseudovirus-based neutralization assay (PBNA) in cells expressing the human angiotensin-converting enzyme-2 (hACE2) receptor for SARS-CoV-2. The assay is reproducible (R2 = 0.96), demonstrates a good dynamic range and high sensitivity. Our data suggest that the biological Anti-SARS-CoV-2 research reagents such as NIBSC 20/130 show lower neutralization against B.1.351 SA (South Africa) and B.1.1.7 UK (United Kingdom) VOC, whereas a commercially available monoclonal antibody MM43 retains activity against both these variants. SARS-CoV-2 spike PBNAs for VOCs would be useful tools to measure the neutralization ability of candidate vaccines in both preclinical models and clinical trials and would further help develop effective prophylactic countermeasures against emerging neutralization escape phenotypes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Spike Pseudoviruses: A Useful Tool to Study Virus Entry and Address Emerging Neutralization Escape Phenotypes

et al. 2021

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“…Vaccination with Ad26.COV2.S triggers neutralizing responses that gradually increase in magnitude and breadth, and potent Fc effector functions and T cell activity, both of which retain activity against variants of concern (Moore et al, 2021;Barouch et al, 2021;Stephenson et al, 2021;Alter et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

Keeton

Richardson

Moyo-Gwete

et al. 2021

Preprint

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The Johnson and Johnson Ad26.COV2.S single dose vaccine, designed as an emergency response to the pandemic, represents an attractive option for the scale-up of COVID-19 vaccination in resource-limited countries. We examined the effect of prior infection with ancestral (D614G) or Beta variants on Ad26.COV2.S immunogenicity approximately 28 days post-vaccination. We compared healthcare workers who were SARS-CoV-2 naive (n=20), to those infected during the first wave prior to the emergence of Beta (n=20), and those infected in the second wave (n=20), when Beta was the dominant variant. We demonstrate that a priming exposure from infection significantly increased the magnitude of spike binding antibodies, neutralizing antibodies and antibody-dependent cellular cytotoxicity activity (ADCC) against D614G, Beta and Delta variants. The magnitude of antibody boosting was similar in both waves, despite the longer time interval between wave 1 infection and vaccination (7 months), compared to wave 2 (2 months). ADCC and binding cross-reactivity was similar in both waves. However, neutralization cross-reactivity varied by wave, showing that the antibody repertoire was shaped by the spike sequence of the infecting variant. Robust CD4 and CD8 T cell responses to spike of similar or higher magnitude as those elicited by infection were induced after vaccination. In contrast to antibody responses, prior infection was not required for the generation of high magnitude T cell responses, and T cell recognition of the Beta variant was fully preserved. Therefore, Ad26.COV2.S vaccination following prior infection, even >6 months previously, may result in substantially enhanced protection against COVID-19, of particular relevance in settings of high SARS-CoV-2 seroprevalence. Furthermore, the dominant impact of the infecting variant on neutralization breadth after vaccination has important implications for the design of second-generation vaccines based on variants of concern.

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“…The vaccine has to be injected IMintramuscularly and the cloned AdV will attach to myocytes, fibroblasts, dendritic cells, macrophages and further cells near the injection site as antigen-presenting cells [ 29 ]. The cloned virus induces a strong immune response [ 36 ] especially after the second boost injection of the vaccine with a broad T-cell immune response and production of IgG antibodies [ 37 ] that are distributed by the lymphogenic and haematogenic route. In blood AdV will attach to all cells, including erythrocytes [ 38 ] and platelets, heparan, heparan sulfate, glycosaminoglycan [ 29 ], and activate platelets [ 34 ], form complexes, that might attach to endothelial cells and induce cytokine release [ 5 , 31 ].…”

mentioning

confidence: 99%

Cerebral venous thrombosis after COVID-19 vaccination: is the risk of thrombosis increased by intravascular application of the vaccine?

Gürtler

Seitz²,

Schramm

2021

Infection

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Keywords Venous thrombosis • SARS-CoV-2 vaccination • Adenovirus vector • PF4 antibody • ThrombocytopeniaCurrently, an unprecedented campaign of vaccination against COVID-19 is carried out worldwide, involving many millions of people. Pre-licensing clinical studies of new vaccines can include only a limited number of subjects; therefore rigorous pharmacovigilance is warranted to detect rare side effects.The surveillance of the recombinant adenovirus-based COVID-19 vaccine ChAdOx1-S (Oxford, Astra-Zeneca) which contains chimpanzee adenovirus (AdV) encoding the SARS-CoV-2 spike glycoprotein, revealed rare thromboses with concurrent thrombocytopenia, including venous thromboses in unusual sites such as cerebral venous sinus thrombosis (CVST), intestinal venous and arterial thromboses [1]. Soon thereafter, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) reported also a signal concerning thromboembolic events with thrombocytopenia after vaccination with the Ad26.COV2-S COVID-19 vaccine (Johnson & Jonhnson) [2], which contains the cloned SARS-CoV-2 spike glycoprotein in AdV type 26. Both above-mentioned vaccines are abbreviated in the following as AdV-S. The above described thrombotic complications after AdV-S have in the meantime Rainer Seitz retired from Paul-Ehrlich-Institute.

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Durable Humoral and Cellular Immune Responses 8 Months after Ad26.COV2.S Vaccination

Cited by 211 publications

References 5 publications

SARS-CoV-2 Spike Pseudoviruses: A Useful Tool to Study Virus Entry and Address Emerging Neutralization Escape Phenotypes

SARS-CoV-2 Spike Pseudoviruses: A Useful Tool to Study Virus Entry and Address Emerging Neutralization Escape Phenotypes

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

Cerebral venous thrombosis after COVID-19 vaccination: is the risk of thrombosis increased by intravascular application of the vaccine?

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