Researchers at the University of Oxford have today published in Preprints with The Lancet an analysis of further data from the ongoing trials of the vaccine.
In this, they reveal that the vaccine efficacy is higher at longer prime-boost intervals, and that a single dose of the vaccine is 76% effective from 22- to up to 90-days post vaccination.
In this preprint, which is currently under review at The Lancet, they report on an analysis of additional data to include information from the trial up to the 7th December 2020, which includes a further 201 cases of primary symptomatic COVID-19 (332 cases from 131 reported in previously).
They report that the effect of dosing interval on efficacy is pronounced, with vaccine efficacy rising from 54.9% with an interval of less than six weeks to 82.4% when spaced 12 or more weeks apart.
They also detail that a single standard dose of the vaccine is 76% effective at protecting from primary symptomatic COVID-19 for the first 90 days post vaccination, once the immune system has built this protection 22 days after the vaccination, with the protection showing little evidence of waning in this period.
Professor Andrew Pollard, Chief Investigator of the Oxford Vaccine Trial, and co-author, said:
“These new data provide an important verification of the interim data that was used by more than 25 regulators including the MHRA and EMA to grant the vaccine emergency use authorisation.
“It also supports the policy recommendation made by the Joint Committee on Vaccination and Immunisation (JCVI) for a 12-week prime-boost interval, as they look for the optimal approach to roll out, and reassures us that people are protected from 22 days after a single dose of the vaccine.”
The exploratory analyses presented in this preprint suggest that it is the dosing interval and not the dosing level which has a great impact on the efficacy of the vaccine. This is in line with previous research supporting greater efficacy with longer prime-boost intervals done with other vaccines such as influenza, Ebola and malaria.
They also hope to report data regarding the new variants in the coming days, and expect the findings to be broadly similar to those already reported by fellow vaccine developers.
The vast majority of COVID-19 candidate vaccines are designed to target the SARS-CoV-2 spike (S) protein, but the precise vaccine-mediated immune correlates of protection remain to be determined.
Two recent reports from the Oxford COVID-19 vaccine team detail the immune outcomes observed in a phase I/II trial of their ChAdOx1 nCoV-19 vaccine, in which volunteers received a single standard dose or various two-dose regimens.
The ChAdOx1 nCoV-19 vaccine comprises a non-replicating chimpanzee adenovirus vector (ChAdOx1) that is genetically modified to express the full-length S protein of SARS-CoV-2. Trial participants were healthy adults aged between 18 and 55 years, with the paper by Ewer et al. describing the immune responses seen in 88 individuals who received either a single dose of ChAdOx1 nCoV-19 or a control vaccine.
The paper by Barrett et al. details immune responses in 52 volunteers who were vaccinated with a standard dose of ChAdOx1 nCoV-19 and then received a standard dose (n = 20) or half-dose (n = 32) booster 56 days later. Previously published data on trial participants who received two standard doses 28 days apart were also included for comparison.
A key finding in the single-dose paper is that a sole vaccination induced S-protein-reactive CD4+ T and CD8+ T cells with a T helper 1 (TH1)-type cytokine bias as well as CD8+ T cells with a cytotoxic phenotype.
This is important as TH1-type immunity is thought to mediate protective antiviral immunity whereas TH2-type responses have been linked with potentially adverse vaccine effects. Robust B cell activation and proliferation were also observed after a single dose and anti-S protein IgG (predominantly the TH1-associated IgG1 and IgG3 isotypes) were detected by day 14 and maintained at day 56.
Notably, these antibodies showed neutralizing activity against SARS-CoV-2 and their avidity for the S protein increased between days 28 and 56. A single vaccination also induced S protein-specific IgM and IgA. No sex-specific or age-related differences in vaccine responses were observed.
The two-dose paper shows that a second vaccination enhances the titres of anti-S antibodies and their neutralizing activity and further promotes TH1-type T cell responses. Moreover, the booster dose enhances the functional capacity of anti-S antibodies to support antibody-dependent phagocytosis, complement deposition and natural killer cell activation, which have been linked with protective immunity in preclinical studies and with better survival of hospitalized patients with COVID-19.
Boosting with a half dose was found to be less effective than a standard dose boost, but giving a second standard dose at day 56 had a similar immune-enhancing effect to a second standard dose given at day 28.
Importantly, the second dose of the vaccine was shown to be safe and, in fact, better tolerated than the prime dose. This contrasts to what has been observed for booster shots with other COVID-19 vaccines.
a two-dose regimen for the vaccine is more effective at promoting immunity to SARS-CoV-2 and also likely to be well tolerated … the booster dose should still be effective if delivered at 8 weeks
The authors conclude that a two-dose regimen for the vaccine is more effective at promoting immunity to SARS-CoV-2 and also likely to be well tolerated. Moreover, these data suggest that the booster dose should still be effective if delivered at 8 weeks after the initial vaccination.
Original articles
- Barrett JR, et al. Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses. Nat. Med. 2020 doi: 10.1038/s41591-020-01179-4. [PubMed] [CrossRef] [Google Scholar]
- Ewer KJ, et al. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat. Med. 2020 doi: 10.1038/s41591-020-01194-5. [PubMed] [CrossRef] [Google Scholar]
More information: COVID Vaccine Trial, Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine. Available at SSRN: ssrn.com/abstract=3777268
