Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial
Fecha
2020Autor
Folegatti, Pedro M
J Ewer, Katie
Aley, Parvinder K
Angus, Brian
Becker, Stephan
Belij-Rammerstorfer, Sandra
Bellamy, Duncan
Bibi, Sagida
Bittaye, Mustapha
Clutterbuck, Elizabeth A
Dold, Christina
Faust, Saul N
Finn, Adam
Flaxman, Amy L
Hallis, Bassam
Heath, Paul
Jenkin, Daniel
Lazarus, Rajeka
Makinson, Rebecca
Minassian, Angela M
Pollock, Katrina M
Ramasamy, Maheshi
Robinson, Hannah
Snape, Matthew
Tarrant, Richard
Voysey, Merryn
Green, Catherine
Douglas, Alexander D
Hill, Adrian V S
Lambe, Teresa
Gilbert, Sarah C
Pollard, Andrew J
Documentos PDF
Resumen
Background The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by
vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that
expresses the spike protein of SARS-CoV-2.
Methods We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee
adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal
conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed
SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose
of 5×10¹⁰ viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites
allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised,
unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered
28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised
total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2
neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80,
and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo
interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of
symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events.
Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after
vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune
responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606.
Findings Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either
ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1
nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and
many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache,
and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19
group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood
mononuclear cells, IQR 493–1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU],
96–317; n=127), and were boosted following a second dose (639 EU, 360–792; n=10). Neutralising antibody responses
against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in
35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of
nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly
with antibody levels measured by ELISA (R²=0·67 by Marburg VN; p<0·001).
Interpretation ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody
responses. These results, together with the induction of both humoral and cellular immune responses, support largescale evaluation of this candidate vaccine in an ongoing phase 3 programme.
Funding UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health
Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland’s NIHR Clinical
Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen.
Palabras clave
ChAdOx1 nCoV-19 vaccine; CoV-19; VaccineEnlace al recurso
https://doi.org/10.1016/Colecciones
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