AstraZeneca's COVID-19 vaccine shows midphase promise in seniors

A phase 2 clinical trial has found AstraZeneca’s COVID-19 vaccine delivers similar immune responses in people aged over and under 70 years. The update, which suggests the vaccine is better tolerated by seniors, provides further evidence that prophylactics may work in the people most vulnerable to the coronavirus.

This week, Pfizer has reported 94% efficacy in people aged over 65 years, and Moderna has said the effectiveness of its vaccine is consistent across subgroups. The updates go some way toward quelling fears that vaccines will fail the population that most needs protecting from SARS-CoV-2.

AstraZeneca, which could be the next company to drop phase 3 data, added to the evidence on the use of COVID-19 vaccines in older adults in a paper published in The Lancet. The paper reported data on 560 people enrolled in the phase 2 portion of the phase 2/3 clinical trial of the ChAdOx1 nCoV-19 vaccine AstraZeneca is developing with the University of Oxford. 

Investigators gave the vaccine, also known as AZD1222, to 200 people aged 70 years and older. A further 40 people in that age group received the control vaccine, MenACWY. The clinical trial also randomized 160 people aged 18 to 55 years and 160 people aged 56 to 69 years to receive either the COVID-19 or control vaccines.

Immunogenicity was similar in all three groups. People of all ages experienced a specific antibody response to the SARS-CoV-2 spike protein and receptor-binding domain 28 days after getting the first vaccine dose. Antibody titers rose in all three cohorts after the booster shot. Neutralizing antibody responses were similar across age groups, as were spike-specific T-cell responses.

The immune responses in older adults are encouraging given the body of evidence that vaccines can trigger relatively weak responses in seniors. However, there are limitations to what can be concluded from the data. The paper lacks data on whether the immune responses confer protection against the coronavirus, and the older cohort may not be representative of the broader population of seniors.

With a median age of 73 to 74 years, the people in the older cohort are younger than many of the individuals likely to be first to receive COVID-19 vaccines. The U.K. vaccination schedule, for example, calls for people in care homes to be vaccinated first, followed by the over-80s and then the over-75s. 

People in the study cohort are also likely healthier than the average senior. As the trial took place amid a national lockdown, the protocol excluded individuals with substantial comorbidities or clinical frailty. The phase 3 trial, which an Oxford professor said will “definitely” read out by Christmas, has a more diverse population and will show whether the immune responses translate into fewer cases of symptomatic COVID-19.

For now, the signs in seniors are encouraging. As well as seeing similar immunogenicity across age groups, the phase 2 found the vaccine has a lower reactogenicity profile in older adults. In the 18-to-55 cohort, 8% of people reported severe fatigue after the first dose. Six percent of participants reported severe chills and “feverish” symptoms. 

There were no severe cases of those reactions in the over-70 group after the first dose and only one severe reaction of any kind, malaise. Nobody over 70 experienced a severe reaction after the boost dose. The only reaction to affect most older people after either dose was tenderness. That is in contrast to people in the younger cohort, most of whom reported some degree of tenderness, pain, muscle ache, fatigue or headache after the first dose. 

No participants in the trial had suspected unexpected serious adverse reactions. As the authors of The Lancet paper note, suspected unexpected serious adverse reactions have been seen in the phase 3 trial, leading to a delay to that study. The reactions will be reported in detail in a future paper.