Author Correction: Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses

Barrett, Jordan R.; Belij‐Rammerstorfer, Sandra; Dold, Christina; Ewer, Katie; Folegatti, Pedro M.; Gilbride, Ciaran; Halkerston, Rachel; Hill, Jennifer; Jenkin, Daniel; Stockdale, Lisa; Verheul, Marije K.; Aley, Parvinder K.; Angus, Brian; Bellamy, Duncan; Berrie, Eleanor; Bibi, Sagida; Bittaye, Mustapha; Cavell, Breeze E.; Clutterbuck, Elizabeth A.; Edwards, Nick J.; Flaxman, Amy; Fuskova, Michelle; Gorringe, Andrew; Hallis, Bassam; Kerridge, Simon; Lawrie, Alison M.; Linder, Aline; Liu, Xinxue; Madhavan, Meera; Makinson, Rebecca; Mellors, Jack; Minassian, Angela M.; Moore, Maria; Farooq, Yama G; Plested, Emma; Poulton, Ian; Ramasamy, Maheshi; Robinson, Hannah; Rollier, Christine S.; Song, Rinn; Snape, Matthew D; Tarrant, Richard; Taylor, Stephen; Thomas, Kelly M.; Voysey, Merryn; Watson, Marion E. E.; Wright, Daniel; Douglas, Alexander D.; Green, Catherine; Avs., Hill; Lambe, Teresa; Gilbert, Sarah C.; Pollard, Andrew J.; Aboagye, Jeremy; Alderson, Jennifer; Ali, Aabidah; Allen, Elizabeth; Allen, Lauren; Anslow, Rachel; Arancibia‐Cárcamo, Carolina V.; Arbe-Barnes, Edward H.; Baker, Megan; Baker, Philip; Baker, Natalie; Baleanu, Ioana; Barnes, Eleanor; Bates, Louise; Batten, Alexander; Beadon, Kirsten; Beckley, Rebecca; Beveridge, Amy; Bewley, Kevin R.; Bijker, Else M.; Blackwell, Luke; Blundell, Caitlin L.; Bolam, Emma; Boland, Elena; Borthwick, Nicola; Boyd, Amy; Brenner, Tanja; Brown, Philip N.; Brown-O’Sullivan, Charlie; Brunt, Emily; Burbage, Jamie; Buttigieg, Karen; Byard, Nicholas; Puig, Ingrid Cabrera; Camara, Susana; Cao, Michelangelo; Cappuccini, Federica; Carr, Melanie; Carroll, Miles W.; Chadwick, Jim; Chelysheva, Irina; Cho, Jee-Sun; Cifuentes, Liliana; Clark, Elizabeth; Colin-Jones, Rachel; Conlon, Christopher P.; Coombes, Naomi; Cooper, Rachel; Crocker, Wendy E. M.; Cunningham, Christina J.; Damratoski, Brad E.; Datoo, M; Datta, Chandrabali; Davies, H. Dele; Demissie, Tesfaye; Maso, Claudio Di; DiTirro, Danielle; Dong, Tao; Donnellan, Francesca R.; Douglas, Naomi; Downing, Charlotte; Drake, Jonathan; Drake-Brockman, Rachael; Drury, Ruth; Dunachie, Susanna; Muhanna, Omar El; Elias, Sean C.; Elmore, Michael J.; Emary, Katherine R. W.; English, Marcus Rex; Felle, Sally; Feng, Shuo; Silva, Carla Ferreira Da; Field, Samantha; Fisher, Richard; Ford, Karen; Fowler, Jamie; Francis, Emma; Frater, John; Furze, Julie; Galian-Rubio, Pablo; Garlant, Harriet; Godwin, Kerry; Gorini, Giacomo; Gracie, Lara; Gupta, Gaurav; Hamilton, Elizabeth; Hamlyn, Joseph; Hanumunthadu, Brama; Harris, Stephanie A.; Harrison, Daisy; Hart, Thomas C.; Hawkins, Sophia; Henry, John A.; Hodges, Gina; Hodgson, Susanne H.; Hou, Mimi M.; Howe, Elizabeth; Howell, Nicola; Huang, Ben; Humphries, Holly E.; Iveson, Poppy; Jackson, Susan; Jackson, Frederic; Jauregui, Sam; Jeffery, Katie; Jones, Elizabeth; Jones, Kathryn L.; Kailath, Reshma; Keen, Jade; Kelly, Sarah; Kelly, Dearbhla M.; Kelly, Elizabeth J.; Kerr, David; Khan, Liaquat; Khozoee, Baktash; Killen, Annabel; Kinch, Jasmin; King, Thomas; King, Lloyd; Kingham-Page, Lucy; Klenerman, Paul; Knight, Julian C.; Knott, Daniel; Koleva, Stanislava; Larkworthy, Colin W.; Larwood, Jessica P. J.; Lees, Emily A.; Lelliott, Alice; Leung, Stephanie; Li, Yuanyuan; Lias, Amelia M.; Lipworth, Samuel; Liu, Shuchang; Loew, Lisa; Ramon, Raquel Lopez; Mallett, Garry; Mansatta, Kushal; Marchevsky, N; Marinou, Spyridoula; Marlow, Emma; Marshall, Julia; Matthews, Philippa C.; McEwan, J; McGlashan, Joanna; McInroy, Lorna; Meddaugh, Gretchen; Mentzer, Alexander J.; Mirtorabi, Neginsadat; Morey, Ella; Morgans, Roisin; Morris, Susan; Morrison, Hazel; Morshead, Gertraud; Morter, Richard; Moya, Nathifa; Mukhopadhyay, Ekta; Muller, Jilly; Munro, Claire; Murphy, Sarah; Mweu, Philomena; Noé, Andrés; Nugent, Fay L.; Nuthall, Elizabeth; O’Brien, Katie M.; O’Connor, Daniel; O’Donnell, Denise; Oguti, Blanché; Olchawski, Vicki; Oliveria, Catarina; O’Reilly, Peter; Osborne, P; Owino, Nelly; Parker, Kaye; Parracho, Helena; Patrick-Smith, Maia; Peng, Yanchun; Penn, Elizabeth J.; Álvarez, Marco Polo Peralta; Perring, James; Petropoulos, Christos J.; Pfafferott, Katja; Pipini, Dimitra; Phillips, Daniel J.; Proud, Pamela C.; Provstgaard-Morys, Samuel; Pulido, David; Radia, Kajal; Rajapaksa, Durga; Lopez, Fernando Ramos; Ratcliffe, Helen; Rawlinson, Thomas A.; Pabon, Emilia Reyes; Rhead, Sarah; Ritchie, Adam; Roberts, Hannah; Roche, Sophie; Rudiansyah, Indra; Salvador, Stephannie; Sanders, Helen; Sanders, Katherine; Satti, Iman; Schmid, Annina; Schofield, Ella; Screaton, Gavin; Sedik, Cynthia; Shaik, Imam H.; Sharpe, Hannah; Shea, Adam; Silk, Sarah E.; Silva-Reyes, Laura; Skelly, Donal; Smith, Catherine C.; Smith, David J.; Spencer, Alexandra J.; Stafford, E. E.; Szigeti, Anna; Tahiri-Alaoui, Abdessamad; Tanner, Rachel; Taylor, Iona J.; Taylor, Keja; Naudé, Rebecca te Water; Themistocleous, Andreas C.; Themistocleous, Andreas; Thomas, Merin; Thomas, Tonia M.; Thompson, Amber; Tinh, Lan; Tomić, Adriana; Tonks, Susan; Towner, James; Tran, Nguyen; Tree, Julia A.; Truby, Adam; Turner, Cheryl; Turner, Nicola; Ulaszewska, Marta; Varughese, Rachel; Vichos, Iason; Walker, Laura; Wand, Matthew E.; White, Caroline; White, Rachel; Williams, Paul V.; Worth, Andrew; Wrin, Terri; Yao, Xin; Zizi, Dalila

doi:10.1038/s41591-021-01372-z

Cited by 11 publications

(14 citation statements)

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“…In line with previous studies, the second dose of AZD1222 substantially enhanced the initial antibody response in our cohort ( 19 , 36 , 44 ). Because the formation of antibodies is physiologically supported by specific T cells, we assumed a correlation between T cell response and antibody formation.…”

Section: Discussionsupporting

confidence: 93%

“…This discrepancy could be either explained by the inability of the Abbott and sVNT assays to distinguish such small changes in antibody concentration or the possibility that the Roche assay detects not only quantitative but also qualitative changes of the antibodies formed. Because previous studies failed to demonstrate a continuous increase in antibody levels for AZD1222 later than 3 weeks after vaccination, the Roche total antibody sandwich assay may also be sensitive to qualitative changes in nascent antibodies (e.g., antibody maturation), in contrast to the Abbott IgG-specific assay ( 12 , 36 ). This hypothesis is also supported by the observation that in direct comparison with the sVNT, the Roche assay underestimated inhibitory capacities at week 3 ( Fig.…”

Section: Discussionmentioning

confidence: 99%

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The Comparability of Anti-Spike SARS-CoV-2 Antibody Tests is Time-Dependent: a Prospective Observational Study

et al. 2022

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This work showed that the comparability of apparently standardized SARS-CoV-2 antibody assays (Roche, Abbott; both given in BAU/mL) after vaccination depends on the time of blood withdrawal. Initially (3 weeks after the first dose AZD1222), there were 3 times higher values in the Abbott assay, but this relationship inversed before boosting (11 weeks after the first dose) with Roche 2 times greater than Abbott.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

The Comparability of Anti-Spike SARS-CoV-2 Antibody Tests is Time-Dependent: a Prospective Observational Study

et al. 2022

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“…For both vaccines, the gene coding for the SARS-CoV-2 spike protein is introduced into an adenovirus vector. The main difference between these two vector vaccines is that Sputnik-V uses two different vectors, the rAd26 for priming and Ad5 in the booster dose ( 27 ), while AstraZeneca includes the spike protein gene in the ChAdOx1 viral vector ( 28 , 29 ).…”

Section: Discussionmentioning

confidence: 99%

Comparison of IgA, IgG, and Neutralizing Antibody Responses Following Immunization With Moderna, BioNTech, AstraZeneca, Sputnik-V, Johnson and Johnson, and Sinopharm’s COVID-19 Vaccines

et al. 2022

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In an ongoing multinational trial, we obtained blood samples from 365 volunteers vaccinated with mRNA vaccines (Moderna, BioNTech), viral DNA-vectored vaccines (AstraZeneca, Sputnik-V, and Johnson and Johnson), or the attenuated virus vaccine from Sinopharm. After collecting reactogenicity data, the expression of S-Protein binding IgG and IgA was analyzed using an automated sandwich ELISA system. Serum neutralizing potentials were then investigated using an ACE-2-RBD neutralizing assay. Moderna’s vaccine induced the highest amounts of SARS-CoV-2 specific neutralizing antibodies compared to the other groups. In contrast, Sinopharm and Johnson and Johnson’s vaccinees presented the lowest SARS-CoV-2-specific antibody titers. Interestingly, moderate to high negative correlations between age and virus-specific IgG expression were observed in the Johnson and Johnson (ρ =-0.3936) and Sinopharm (ρ =-0.6977) groups according to Spearman’s rank correlation analysis. A negative correlation was seen between age and IgA expression in the Sputnik-V group (ρ =-0.3917). The analysis of virus neutralization potentials in age categories demonstrated that no significant neutralization potential was observed in older vaccinees (61and 80 years old) in the Sputnik-V Johnson and Johnson and Sinopharm vaccinees’ groups. In contrast, neutralization potentials in sera of Moderna, BioNTech, and AstraZeneca vaccinees were statistically comparable in all age categories. Furthermore, while the AstraZeneca vaccine alone induced moderate IgG and IgA expression, the combination with Moderna or BioNTech mRNA vaccines induced significantly higher antibody levels than a double dose of AstraZeneca and similar IgG expression and neutralization potential compared to Moderna or BioNTech vaccines used alone. These results suggest that mRNA vaccines are the most immunogenic after two doses. DNA vectored vaccines from AstraZeneca and Sputnik-V presented lower but significant antibody expression and virus neutralizing properties after two doses. The lowest antibody and neutralization potential were observed in the Sinopharm or Johnson and Johnson vaccinees. Especially elderly over 60 presented no significant increase in neutralizing antibodies after vaccination. The data also indicate that heterologous vaccination strategies combining the AstraZeneca DNA vectored vaccines and mRNA vaccines are more effective in the induction of neutralizing antibodies compared to their homologous counterparts.

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“…To date, vaccination is considered the key strategy for ending the pandemic. 3 Approved vaccines among others include the adenovirus-based ChAdOx1 nCoV-19 (Vaxzevria, AstraZeneca) and mRNA-based BNT162b2 (Comirnaty, BioNTech/Pfizer), which induce humoral and cellular immunological responses 4 , 5 , 6 , 7 (and preprint: 8 ), showed high efficacy in clinical trials, 9 , 10 and potent protection from COVID-19 in real-world settings. 11 , 12 However, the occurrence of rare thrombotic events with thrombocytopenia after ChAdOx1 nCoV-19 vaccinations, especially in individuals younger than 60 years, associated with the generation of auto-platelet factor 4 antibodies, halted vaccination of this group with ChAdOx1 nCoV-19 in some countries.…”

Section: Introductionmentioning

confidence: 99%

Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants

et al. 2022

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Background Heterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited. Methods To evaluate the reactogenicity and humoral as well as cellular immune responses towards most prevalent SARS-CoV-2 variants after a heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, we analysed a cohort of 26 clinic employees aged 25-46 (median 30.5) years who received a ChAdOx1 nCoV-19 prime followed by a BNT162b2 boost after an 8-week interval. Serological data were compared to a cohort which received homologous BNT162b2 vaccination with a 3-week interval (14 individuals aged 25-65, median 42). Findings Self-reported solicited symptoms after ChAdOx1 nCoV-19 prime were in line with previous reports and more severe than after the BNT162b2 boost. Antibody titres increased significantly over time resulting in strong neutralization titres two weeks after the BNT162b2 boost and subsequently slightly decreased over the course of 17 weeks. At the latest time point measured, all analysed sera retained neutralizing activity against the currently dominant Delta (B.1.617.2) variant. Two weeks post boost, neutralizing activity against the Alpha (B.1.1.7) and immune-evading Beta (B.1.351) variant was ∼4-fold higher than in individuals receiving homologous BNT162b2 vaccination. No difference was observed in neutralization of Kappa (B.1.617.1). In addition, heterologous vaccination induced CD4 + and CD8 + T cells reactive to SARS-CoV-2 spike peptides of all analysed variants; Wuhan-Hu-1, Alpha, Beta, Gamma (P.1), and Delta. Interpretation In conclusion, heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination is not associated with serious adverse events and induces potent humoral and cellular immune responses. The Alpha, Beta, Delta, and Kappa variants of spike are potently neutralized by sera from all participants and reactive T cells recognize spike peptides of all tested variants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations and also offers protection against current variants of concern. Funding This project has received funding from the European Union's Horizon 2020 research and innovation programme, the German Research Foundation, the BMBF, the Robert Koch Institute (RKI), the Baden-Württemberg Stiftung, the county of Lower Saxony, the Ministry for Science, Research and the Arts of Baden-Württemberg, Germany, and the National Institutes of Health.

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Author Correction: Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses

Cited by 11 publications

References 0 publications

The Comparability of Anti-Spike SARS-CoV-2 Antibody Tests is Time-Dependent: a Prospective Observational Study

The Comparability of Anti-Spike SARS-CoV-2 Antibody Tests is Time-Dependent: a Prospective Observational Study

Comparison of IgA, IgG, and Neutralizing Antibody Responses Following Immunization With Moderna, BioNTech, AstraZeneca, Sputnik-V, Johnson and Johnson, and Sinopharm’s COVID-19 Vaccines

Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants

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