LONDON – Phase II data on Astrazeneca plc’s AZD-1222 COVID-19 vaccine show it prompts an equivalent immune response in healthy people aged 70, to that seen in people ages 18 to 55, despite the fact the elderly had fewer side effects from vaccination.

The findings, reported in The Lancet, overcome concerns that immuno-senescence would make for weaker responses in older adults.

AZD-1222 (previously ChAdOx1-nCoV-19), a chimpanzee adenovirus vectored vaccine, is the fifth COVID-19 vaccine for which data on the immune response in older adults has been published. Moderna Inc.’s mRNA vaccine also showed similar responses in young and old adults, while Pfizer Inc. and Biontech SE’s mRNA vaccine, Cansino Biologic Inc.’s single-dose human adenovirus vaccine and Sinopharm Group Co. Ltd.’s inactivated virus vaccine all recorded lower responses in older adults compared to younger people.

“It’s really important the vaccine works in people over 65,”said Sarah Gilbert, professor of virology and project leader at Oxford University. “The first data are really encouraging, showing we are getting very good immune responses, even in the over 70s. They look very similar to those in younger adults.”

The study, conducted at two sites at Oxford and Southampton, started by inoculating healthy participants, ages 18 to 55, later extending the age range to 56 to 69 and then 70-plus. “A really important finding is that it is much better tolerated as [participants] get older,” Gilbert told attendees of a briefing held to discuss the results.

Across all age groups, T cells against SARS-CoV-2 peaked – as expected – 14 days after the first dose, while antibody levels were greatest 28 days after the second injection. Volunteers are still being followed up and it is not known for how long those T-cell and antibody responses are maintained.

It also is unproven if the responses are protective. The phase III trial of AZD-1222 was one of the first to get off the ground, but began recruiting in the U.K. just as the infection level in the population was going down from the peak in April, meaning it was slow to accumulate confirmed cases of COVID-19.

Two other arms are running in Brazil and South Africa. With infections in the U.K. rising again since the beginning of September, Andrew Pollard, chief investigator, said the 53 confirmed cases of COVID-19 that must accrue for the interim analysis will be reached before the end of the year.

The phase II results for AZD-1222 are chasing a blizzard of positive data this week, with Pfizer reporting efficacy of 95% when it published headline results from its completed phase III, and Moderna saying it saw 95% efficacy in its phase III interim analysis. There also was other encouraging phase II data, with Sinovac Biotech Ltd. reporting that Coronavac, a COVID-19 vaccine based on an inactivated whole SARS-CoV-2 virus, is safe and induces an antibody response in healthy volunteers ages 18 to 59.

Pollard said the timing of the AZD-1222 phase II results hinged on submitting the paper for peer review before publication, and was not influenced by the announcement of any of the other vaccines data. “As academics, it’s a really important part of the process. We want to ensure our data is reviewed, because this [vaccine] could be used around the world,” he said.

Correlates of protection

In the AZD-1222 phase II, there were 160 people ages 18 to 55, 160 ages 56 to 69 and 240 ages 70 or over. They were split into 10 groups, which received either AZD-1222 at a low or standard dose, or a meningococcal conjugate vaccine as control. Participants older than 55 were also split into groups and either given a single dose of vaccine, or two doses 28 days apart.

Study recruitment occurred during a national lockdown in the U.K. when vulnerable individuals were advised to self-isolate. For that reason, the study includes only healthy participants and not those with co-morbidities, or who are frail. However, people in vulnerable groups are taking part in the phase III.

Participants ages 18 to 55 who received two standard doses of the COVID-19 vaccine and all participants 56 or older had their immune responses assessed on the day of vaccination, then one, two and four weeks after their first and second vaccinations. They will continue to be monitored for any serious adverse events for one year following final vaccination.

Maheshi Ramasamy, consultant physician and principal investigator, said there was concern the milder side-effect profile seen in older people would mean the immune response was weak. “Immuno-senescence is a real problem,” she said.” It’s a real challenge to boost the immune response in the elderly, so we are particularly encouraged to see good immune responses – but we don’t know why [this is happening].”

It is not known if the immune response in older people will remain strong over time. Gilbert said that in an earlier single-dose study she carried out using the chimpanzee adenoviral vector to deliver a flu vaccine, there was a good initial response, but it was not maintained at one year.

“We might need to boost more often in older people, but we are not thinking that would be more than once a year,” Gilbert said.

It is hoped the phase III results will show what the correlates of protection are. “We can then see at what point the reaction drops below what is protective: we don’t want to vaccinate more than we need,” said Gilbert.

While running slightly behind Moderna and Pfizer’s COVID-19 vaccines, Gilbert said AZD-1222 has the advantage that the manufacturing technology can be rolled out less expensively. Astrazeneca has partners around the world producing the vaccine at volume.

AZD-1222 also is more stable than mRNA vaccines and can be stored in regular vaccine fridges and could be delivered worldwide using existing cold chain infrastructure.

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