Researchers from AstraZeneca, the University of Oxford, and several collaborating institutions have published Phase II data showing that their COVID-19 vaccine candidate AZD1222—one of several leading vaccines in development against the virus—has similar immunogenicity across all age groups after the second “boost” dose, including older adults where the vaccine showed fewer adverse effects.

“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,” the researchers concluded in “Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomized, controlled, Phase II/III trial,” published Thursday in The Lancet.

While people in all age groups are at risk of contracting COVID-19, older people “face significant risk of developing severe illness,” according to the World Health Organization.

Oxford Vaccine group director Andrew J. Pollard, MBBS, PhD, the study’s chief investigator, and Maheshi Ramasamy, DPhil, investigator at the Oxford Vaccine Group, consultant physician, and the study’s corresponding author, co-led the team of researchers that carried out the Phase II trial (NCT04400838  and ISRCTN Registry No. ISRCTN15281137).

The study assessed AZD1222 in 560 participants—of which 160 were aged 18–55 years, 160 aged 56–69 years, and 240 aged 70 or over. Participants were split into 10 groups, where they received either AZD1222 at a low dose (2·2 × 10¹⁰ virus particles) or a standard dose (3·5–6·5 × 10¹⁰ virus particles)—or the meningococcal conjugate vaccine MenACWY, which served as the trial’s control. Participants who were over 55 years old were also split into groups and either given a single dose of vaccine, or two doses 28 days apart.

AZD1222 is based on an adenovirus vaccine vector and the COVID-19 spike protein. After vaccination, the surface spike protein of the coronavirus is produced, which primes the immune system to attack the coronavirus if it later infects the body.

AZD1222 is among 19 “Front Runner” leading candidates among the more than 300 COVID-19 therapeutics under study in GEN’s “COVID-19 Drug & Vaccine Candidate Tracker.”

Inducing immune responses

In the Phase II trial, AZD1222 induced immune responses in both parts of the immune system in all age groups, as well as at both the low and standard doses. Median anti-spike SARS-CoV-2 IgG responses observed 28 days after the boost dose were similar across the three age cohorts: 20,713 arbitrary units [AU]/mL in 39 18–55 year-olds; 16,170 AU/mL in 26 56–69 year-olds; and 17,561 AU/mL in 47 participants aged 70 or older.

The vaccine provoked a T-cell response within 14 days of the prime vaccination dose, as well as an antibody response within 28 days of the boost dose, having been shown to find and attack the virus when it was circulating in the blood or lymphatic system.

All but one of 209 participants receiving the boost dose showed neutralizing antibody responses 14 days after the boost dose. T-cell responses peaked at day 14 after a single standard dose of AZD1222, with 24 participants aged 18–55 years showing a median 1,187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells; 29 56–69 year-olds, 797 SFCs; and 48 participants aged 70 and older, 977 SFCs.

Neutralizing antibody titers after a boost dose were similar across all age groups. The microneutralization assay MNA80 at day 42 in the standard-dose groups yielded median results of 193 in 39 participants aged 18–55 years; 144 in 20 participants aged 56–69 years; and 161 in 47 participants aged ≥70 years.

“The robust antibody and T-cell responses seen in older people in our study are encouraging,” Ramasamy said in a statement. “We hope that this means our vaccine will help to protect some of the most vulnerable people in society, but further research will be needed before we can be sure.”

Researchers are seeking to confirm their Phase II findings through a global Phase III trial (NCT04516746) that had an estimated enrollment of 40,051 participants as of November 13, according to its page on The Phase III trial has resumed recruitment of U.S. patients last month following a pause triggered by a patient illness that AstraZeneca later said was not related to AZD1222. The trial is designed to assess the vaccine’s effectiveness in protecting against infection with SARS-CoV-2 in people that include older adults with underlying health conditions.

“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,” Pollard stated.

Fewer local, systemic symptoms

Adults 70 years of age and older showed fewer adverse effects than participants in the two younger adult groups. Local symptoms—which included temporary injection-site pain, tenderness, warmth, redness, swelling, induration, and itch—occurred in 88% of 18–55 year-olds (43 of 49 participants); 73% of 56–69 year-olds (22 of 30), and 61% of participants aged 70 or over (30 of 49).

Within seven days of injection, systemic symptoms—which included malaise, muscle ache, joint pain, fatigue, nausea, headache, chills, and self-reported or measured “objective” fever of 38°C (100.4° F) or higher occurred in 86% of 18–55 year-olds (42 of 49 participants), 77% of 56–69 year-olds (23 of 30), and 65% of people aged 70 or over (32 of 49).

“We were pleased to see that our vaccine was not only well tolerated in older adults; it also stimulated similar immune responses to those seen in younger volunteers,” Ramasamy said. “The next step will be to see if this translates into protection from the disease itself.”

Among participants aged 18–55 years, 100 were assigned to AZD1222, the other 60 to the meningococcal conjugate vaccine. Of those aged 56–69 years, 120 received the AstraZeneca-Oxford vaccine, the other 40 received control. And of the 240 participants aged 70 and older, 200 were randomized to AZD1222, the other 40 to control.

The co-authors acknowledged several limitations to their study:

  • Participants aged 70 and older had an average age of 73–74 years and few underlying health conditions, so may not be representative of the general older population. Larger studies are in progress to assess immunogenicity, safety, and efficacy in older adults with a wider range of comorbidities.
  • Nearly all participants of all ages were white, non-smokers, and may not be representative of the general population. However, people from a range of backgrounds, countries, and ethnicities are being included in the Phase III trial of AZD1222.

“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,” Melissa Andrew, MD, PhD, staff geriatrician and associate professor of geriatric medicine at Dalhousie University in Halifax, Nova Scotia, Canada, wrote in a commentary linked to the study. “Older adults (across the full spectrum of frailty) and those who care about them are eagerly awaiting this progress towards safe and effective COVID-19 vaccines.”

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