COVID-19 vaccines as effective in older adults
With more trial data on COVID-19 vaccine pouring in, reports for at least two leading COVID-19 vaccine candidates, the mRNA-1273 vaccine and the adenovirus-vectored ChAdOx1 nCoV-19 vaccine, have indicated that they may also be effective in older individuals — a population known to be at a heightened risk of severe COVID-19 illness.
“Immune responses from vaccines are often lessened in older adults because the immune system gradually deteriorates with age, which also leaves older adults more susceptible to infections. As a result, it is crucial that COVID-19 vaccines are tested in this group who are also a priority group for immunization,” said Professor Andrew Pollard, University of Oxford, UK, lead author of the COV002 study on ChAdOx1 nCoV-19 vaccine.
In the phase II/III COV002 trial, 560 adults aged ≥18 years were randomized to receive intramuscular injection of ChAdOx1 nCoV-19 vaccine at two different doses, and in a one-dose or two-dose regimen. [Lancet 2020;doi:10.1016/S0140-6736(20)32466-1]
After a single standard dose vaccination, ChAdOx1 nCoV-19 induced both arms of the immune responses — antibody and T-cell responses — across all age groups, including those 70 years and older.
Furthermore, antibody responses were boosted with the second vaccination, levels of which were maintained through 28 days after the booster shot. These responses were similar, regardless of age, in terms of neutralizing antibody titres (p=0.40) and anti-spike SARS-CoV-2 IgG responses (p=0.68).
“Immunogenicity was similar across age groups after a boost vaccination,” the researchers pointed out. “By 14 days after the boost dose, [more than 99 percent] of 209 boosted participants had neutralizing antibody responses.”
T-cell response peaked within 14 days, even with just a single vaccination.
“If these responses correlate with protection in humans, these findings are encouraging because older individuals are at disproportionate risk of severe COVID-19 and so any vaccine adopted for use against SARS-CoV-2 must be effective in older adults,” said Pollard and co-authors.
Similarly, immune response induction in older adults was also observed with mRNA-1273 vaccination in another phase I expansion study on 40 older adults, stratified according to age 56–70 years or ≥71 years. All participants received two doses of the vaccine, given 28 days apart. [N Engl J Med 2020;doi:10.1056/NEJMoa2028436]
Again, mRNA-1273 vaccination induced both antibody and T-cell responses in all participants in the expansion study — which the investigators noted were similar to those observed among younger participants aged between 18–55 years in the original cohort.
“The data also suggest that a second dose of vaccine is needed to achieve neutralizing antibodies in participants after the age of 56 years, and titres rapidly increased by 7 days after the booster vaccination,” said the investigators.
As immunogenic, but less reactogenic
In the COV002 trial, the researchers found that the ChAdOx1 nCoV-19 vaccine was better tolerated in older participants than younger adults, with both local and systemic reactions occurring less frequently in older adults (aged ≥56 years).
These reactions included headache, injection-site pain, muscle ache, and fever, and were similar in nature to what has been reported previously. “Most of the reported local and systemic adverse events were mild to moderate in severity,” according to the researchers.
Among the participants who received two standard doses of ChAdOx1 nCoV-19, local reactions occurred at a rate of 88 percent in the 18–55 years subgroup, compared with 73 percent in the 56–69 years subgroup and 61 percent in the subgroup aged ≥70 years, after the first vaccination.
For systemic reactions, the rates were 86 percent in the18–55 years subgroup, compared with 77 percent in the 56–69 years subgroup and 65 percent in those aged ≥70 years.
“Fewer adverse events were reported after the boost vaccination than after the prime vaccination and reactogenicity reduced with increasing age. The lower dose of vaccine was less reactogenic than the standard dose of vaccine across all age groups,” observed Pollard and co-authors.
The mRNA-1273 vaccine also showed an acceptable safety profile, with most of the local and systemic adverse events being mild to moderate and of short duration in nature. The most common events included headache, fatigue, myalgia, chills, and injection site pain.
“Such adverse events were dose-dependent and were more common after the second immunization,” the investigators reported. “We did not observe systematic differences in the reactogenicity profile between this older cohort and participants between the ages of 18 and 55 years.”
While the COV002 study answers some of the critical considerations for COVID-19 vaccines as outlined by the WHO — including immunogenicity in at-risk group such as older adults and safety — “questions remain about effectiveness and length of protection, and we need to confirm our results in older adults with underlying conditions to ensure that our vaccine protects those most at risk of severe COVID-19 disease,” said study co-investigator Professor Sarah Gilbert, University of Oxford, UK.
“It is encouraging that more studies in older adult populations are underway and will hopefully bring opportunities to implement nuanced analyses of how underlying health status and frailty affect vaccine safety, reactogenicity, immunogenicity, and efficacy in older adults in real-world settings,” echoed Drs Melissa Andrew and Janet McElhaney from Dalhousie University, Halifax and Health Sciences North Research Institute, Sudbury, Canada, respectively, in a linked commentary. [Lancet 2020;doi:10.1016/S0140-6736(20)32481-8]