tetano
Editor, Senior Moderator
Nat Med
. 2020 Dec 17.
doi: 10.1038/s41591-020-01194-5. Online ahead of print.
T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial
Katie J Ewer[SUP] 1 [/SUP], Jordan R Barrett[SUP] 2 [/SUP], Sandra Belij-Rammerstorfer[SUP] 2 [/SUP], Hannah Sharpe[SUP] 2 [/SUP], Rebecca Makinson[SUP] 2 [/SUP], Richard Morter[SUP] 2 [/SUP], Amy Flaxman[SUP] 2 [/SUP], Daniel Wright[SUP] 2 [/SUP], Duncan Bellamy[SUP] 2 [/SUP], Mustapha Bittaye[SUP] 2 [/SUP], Christina Dold[SUP] 3 [/SUP], Nicholas M Provine[SUP] 4 [/SUP], Jeremy Aboagye[SUP] 2 [/SUP], Jamie Fowler[SUP] 2 [/SUP], Sarah E Silk[SUP] 2 [/SUP], Jennifer Alderson[SUP] 5 [/SUP], Parvinder K Aley[SUP] 3 [/SUP], Brian Angus[SUP] 4 [/SUP], Eleanor Berrie[SUP] 6 [/SUP], Sagida Bibi[SUP] 3 [/SUP], Paola Cicconi[SUP] 3 [/SUP], Elizabeth A Clutterbuck[SUP] 3 [/SUP], Irina Chelysheva[SUP] 3 [/SUP], Pedro M Folegatti[SUP] 2 [/SUP], Michelle Fuskova[SUP] 2 [/SUP], Catherine M Green[SUP] 6 [/SUP], Daniel Jenkin[SUP] 2 [/SUP], Simon Kerridge[SUP] 3 [/SUP], Alison Lawrie[SUP] 2 [/SUP], Angela M Minassian[SUP] 2 [/SUP], Maria Moore[SUP] 3 [/SUP], Yama Mujadidi[SUP] 3 [/SUP], Emma Plested[SUP] 3 [/SUP], Ian Poulton[SUP] 2 [/SUP], Maheshi N Ramasamy[SUP] 3 [/SUP], Hannah Robinson[SUP] 3 [/SUP], Rinn Song[SUP] 3 [/SUP], Matthew D Snape[SUP] 3 [/SUP], Richard Tarrant[SUP] 6 [/SUP], Merryn Voysey[SUP] 3 [/SUP], Marion E E Watson[SUP] 2 [/SUP], Alexander D Douglas[SUP] 2 [/SUP], Adrian V S Hill[SUP] 2 [/SUP], Sarah C Gilbert[SUP] 2 [/SUP], Andrew J Pollard[SUP] 3 [/SUP], Teresa Lambe[SUP] 7 [/SUP], Oxford COVID Vaccine Trial Group
Collaborators, Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed[SUP]1[/SUP]. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses[SUP]2[/SUP] and might reduce the potential for disease enhancement[SUP]3[/SUP]. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection[SUP]4[/SUP]. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. [SUP]5,6[/SUP]). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)[SUP]7[/SUP] given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18-55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4[SUP]+[/SUP] T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8[SUP]+[/SUP] T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.
. 2020 Dec 17.
doi: 10.1038/s41591-020-01194-5. Online ahead of print.
T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial
Katie J Ewer[SUP] 1 [/SUP], Jordan R Barrett[SUP] 2 [/SUP], Sandra Belij-Rammerstorfer[SUP] 2 [/SUP], Hannah Sharpe[SUP] 2 [/SUP], Rebecca Makinson[SUP] 2 [/SUP], Richard Morter[SUP] 2 [/SUP], Amy Flaxman[SUP] 2 [/SUP], Daniel Wright[SUP] 2 [/SUP], Duncan Bellamy[SUP] 2 [/SUP], Mustapha Bittaye[SUP] 2 [/SUP], Christina Dold[SUP] 3 [/SUP], Nicholas M Provine[SUP] 4 [/SUP], Jeremy Aboagye[SUP] 2 [/SUP], Jamie Fowler[SUP] 2 [/SUP], Sarah E Silk[SUP] 2 [/SUP], Jennifer Alderson[SUP] 5 [/SUP], Parvinder K Aley[SUP] 3 [/SUP], Brian Angus[SUP] 4 [/SUP], Eleanor Berrie[SUP] 6 [/SUP], Sagida Bibi[SUP] 3 [/SUP], Paola Cicconi[SUP] 3 [/SUP], Elizabeth A Clutterbuck[SUP] 3 [/SUP], Irina Chelysheva[SUP] 3 [/SUP], Pedro M Folegatti[SUP] 2 [/SUP], Michelle Fuskova[SUP] 2 [/SUP], Catherine M Green[SUP] 6 [/SUP], Daniel Jenkin[SUP] 2 [/SUP], Simon Kerridge[SUP] 3 [/SUP], Alison Lawrie[SUP] 2 [/SUP], Angela M Minassian[SUP] 2 [/SUP], Maria Moore[SUP] 3 [/SUP], Yama Mujadidi[SUP] 3 [/SUP], Emma Plested[SUP] 3 [/SUP], Ian Poulton[SUP] 2 [/SUP], Maheshi N Ramasamy[SUP] 3 [/SUP], Hannah Robinson[SUP] 3 [/SUP], Rinn Song[SUP] 3 [/SUP], Matthew D Snape[SUP] 3 [/SUP], Richard Tarrant[SUP] 6 [/SUP], Merryn Voysey[SUP] 3 [/SUP], Marion E E Watson[SUP] 2 [/SUP], Alexander D Douglas[SUP] 2 [/SUP], Adrian V S Hill[SUP] 2 [/SUP], Sarah C Gilbert[SUP] 2 [/SUP], Andrew J Pollard[SUP] 3 [/SUP], Teresa Lambe[SUP] 7 [/SUP], Oxford COVID Vaccine Trial Group
Collaborators, Affiliations
- PMID: 33335323
- DOI: 10.1038/s41591-020-01194-5
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed[SUP]1[/SUP]. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses[SUP]2[/SUP] and might reduce the potential for disease enhancement[SUP]3[/SUP]. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection[SUP]4[/SUP]. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. [SUP]5,6[/SUP]). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)[SUP]7[/SUP] given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18-55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4[SUP]+[/SUP] T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8[SUP]+[/SUP] T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.