COVID-19 vaccine hope for older adults: following release of AstraZeneca, Pfizer, Moderna clinical trial data
Older adults are at a disproportionate risk of severe COVID-19 - as well as being more likely to be a greater burden on health systems if infected - meaning they will be among those first in line for a vaccine once approved. However, the immune system gradually deteriorates with age, meaning that immune responses from vaccines may be lessened in older adults.
While it can be difficult to compare results between different studies, data now published from leading COVID-19 candidates suggests these vaccines may be effective in older candidates. These vaccines – from AstraZeneca, Pfizer, Moderna and CanSino – have all now reached Phase 3 trials.
AstraZeneca's Phase 2 data
AstraZeneca has published data this week from its Phase 2/3 trial, finding its chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19 or AZD1222) produces a similar immune response across all age groups after the second dose.
The phase 2 component of the study had 560 participants with age ranges as follows: 160 aged 18-55 years, 160 aged 56-69 years, and 240 aged 70 or over. Participants received either the vaccine candidate at a low or standard dose; or a control vaccine (meningococcal conjugate vaccine). Participants aged over 55 years were also split into groups and either given a single dose of vaccine, or two doses 28 days apart.
“The ChAdOx1 nCoV-19 vaccine induced antibodies against the SARS-CoV-2 spike protein and receptor binding domain 28 days after a single low or standard dose across all age groups," reports the study.
The current data uses relatively small sample sizes; and while they may include older people these are not necessarily representative of the oldest generation as a whole (AstraZeneca notes that participants in the oldest age group had an average age of 73-74 years and few underlying health conditions, so may not be representative of the general older population, including those living in residential care settings or over 80 years of age).
Larger scale studies, however, are now underway to evaluate immunogenicity, safety and efficacy in older adults with a wider range of comorbidities.
"Following the booster dose of the vaccine, antibody levels increased at day 56 of the trial, irrespective of dose or participant age. The same was seen with levels of neutralising antibodies at day 42, two weeks after the booster vaccine dose. By 14 days after the boost dose, 208 of 209 (more than 99%) participants (selected from participants of all ages and doses) had neutralising antibody responses.
“T cell responses against the SARS-CoV-2 spike protein peaked 14 days after first vaccination, regardless of age and low or standard vaccine dose.”
The study found the vaccine is better tolerated in older people compared to younger adults, with fewer side effects.
Pfizer: Phase 3 data shows equivalent efficacy across all age groups
Pfizer says its mRNA candidate also has consistent efficacy across age groups. Having concluded its Phase 3 study this month, it found that efficacy in adults over 65 years of age was over 94% - practically equivalent to the figure of 95% across the total study of ages 12+.
Around 41% of trial participants in the 43,000-strong study are aged 56 – 85 years old. Although Pfizer has not released a further breakdown of how many people or how many of the 170 confirmed COVID-19 cases were in older age groups, it has been confident enough to state 94% efficacy for ages 65+.
As with AstraZeneca’s vaccine, older adults tended to report fewer and milder solicited adverse events following vaccination.
Moderna assessing 7,000 people aged 65+ in Phase 3 trial
Moderna’s Phase 1 trial also included 40 older adults (20 aged 56-70 years old; and 20 aged 71+); with two doses of either 25 μg or 100 μg of its mRNA COVID-19 vaccine candidate (mRNA-1273) administered 28 days apart.
Publishing the results of this trial in New England Journal of Medicine in September, it said: “Binding- and neutralizing-antibody responses [in these groups] appeared to be similar to those previously reported among vaccine recipients between the ages of 18 and 55 years and were above the median of a panel of controls who had donated convalescent serum. The vaccine elicited a strong CD4 cytokine response involving type 1 helper T cells.”
Moderna's Phase 3 COVE study for the mRNA vaccine candidate includes more than 7,000 Americans over the age of 65. Its interim analysis, released this week for the first 94 confirmed COVID-19 cases and reporting 94.5% efficacy overall, did not give any indication as to how the vaccine had fared in this population. However, its subsequent analyses should be in a place to do so.
CanSino: Vaccine gives better immune response than found in general population
CanoSino has been slightly more cautious in its efficacy results for older people: but does believe its non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine offers a certain level of protection.
In a study of Phase 2 data published in The Lancet in July, it found that patients aged 55 years or older were associated with 'relatively low antibody responses', and particularly in terms of neutralising antibodies to live virus, both when given a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL (compared to the rest of the study population totalling 508 people aged 18+).
However, it noted that immune responses were still ‘significantly higher’ than those seen in the same age group in the placebo population.