South African study data were used to evaluate the safety of the vaccine in the results just published, but not its efficacy [which refers to the percentage reduction of disease].
"As there were very few Covid-19 cases that occurred in South Africa at least 14 days after volunteers had received their second dose of vaccine, data from South Africa was not included in the pooled efficacy analysis," says Professor Shabir Madhi, Executive Director of the Vaccines and Infectious Diseases Analytics Research Unit (VIDA) at Wits University, who leads the trial in South Africa and who is a joint first author of the paper.
"The results being reported today herald a milestone in the development of Covid-19 vaccines, with the results now having gone through rigorous scientific peer review and being available for interrogation by the general scientific community and the public," he says.
In the paper, University of Oxford and AstraZeneca researchers present a pooled analysis of Phase 3 trials of a vaccine against SARS-CoV-2 across two different dose regimens, resulting in an average efficacy of 70.4%.
The efficacy data are based on 11,636 volunteers across the UK and Brazil, and combined across three groups of people vaccinated - two groups who received a standard dose prime vaccination followed by a standard dose booster vaccination, and one group (in the UK only) who received a low dose prime vaccination followed by a standard dose vaccination.
"The vaccine is also being evaluated in the study amongst 2100 South Africans, who are still being followed up for Covid-19 illness before an analysis can be done in South Africa on the efficacy of the vaccine," says Madhi.
The peer reviewed data further revealed that no hospitalisations or severe disease was observed in the vaccinated groups.
"This Covid-19 vaccine has the greatest prospect of being deployed in low- and middle-income countries in the immediate future compared to the mRNA Covid-19 vaccines," says Madhi. "In addition to its modest cold-storage requirements compared to mRNA vaccines, the Oxford vaccine is also likely to be more available, as it is easier to scale-up in manufacturing capacity, and will likely be the most affordable of the three Covid-19 vaccines for which the safety and efficacy has now been reported."
Professor Andrew Pollard, Director of the Oxford Vaccine Group and Chief Investigator of the Oxford Vaccine Trial, said: "Today, we have published the interim analysis of the phase 3 trial and show that this new vaccine has a good safety record and efficacy against the coronavirus. We are hugely grateful to our trial volunteers for working with us over the past eight months to bring us to this milestone."
The pooled analysis in the study shows that the overall vaccine efficacy at least 14 days after the second dose was 70.4%; the standard dose / standard dose sub-groups showing 62.1% efficacy, and with the low dose / standard dose sub-group demonstrating 90.0% efficacy. No hospitalisations or severe disease were observed in the vaccinated groups.
The authors further report on an extensive safety database from volunteers in the UK, Brazil and South Africa accompanying the efficacy findings; of 24,103 trial volunteers, and 73,480 'person-months' of safety follow up, only three from 170 reported serious adverse events were possibly related to the vaccine.
Of these, one was considered 'possibly related' to the ChAdOx1 nCoV-19 vaccine, one occurred in the control group, and a further case of severe fever in the vaccinated group was considered to be an expected vaccine-related event.
Two updates to the trial protocol are reported by the authors in this publication; the move from the originally planned single dose study to a two-dose study following early immunogenicity results, and the addition of a low dose / standard dose protocol following the observation of difference in the results of quantification methods between delivery of batches of the vaccine.
Of the 11,636 volunteers in the UK and Brazil included in this initial analysis of efficacy, the majority are in the 18-55 age range (UK 87% and Brazil 90%), with those aged 56 or older contributing 12%. As only five cases included in the primary analysis occurred in those who were more than 55 years old, the vaccine efficacy in older age groups could not be assessed but will be determined in future analyses after more cases have accrued in this age range.
The researchers also investigated the potential for the vaccine to prevent asymptomatic disease, through the use of weekly swabbing by UK trial volunteers. These data indicate that the low dose / standard dose vaccine may provide a protection against asymptomatic infection, but stress that these data are at an early phase, with too high a level of uncertainty to be certain that this vaccine will protect against asymptomatic infection.
Further analysis is ongoing into these data, and will be provided to the regulators to enable them to best decide on dose protocols, should this vaccine be granted emergency use authorisation.
Madhi says, "It is essential that the South Africa government is pro-active in pursuing all options to ensure early access - at an affordable price - for large quantities of Covid-19 vaccine to be made available in South Africa, with immunization ideally starting before a widespread resurgence of Covid-19, which I anticipate will be more prevalent in the first quarter of 2021."
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Journal
The Lancet