AstraZeneca/Oxford vaccine shows promise for older adults

About Liz Seegert

Liz Seegert (@lseegert), is AHCJ’s topic editor on aging. Her work has appeared in, Journal of Active Aging, Cancer Today, Kaiser Health News, the Connecticut Health I-Team and other outlets. She is a senior fellow at the Center for Health Policy and Media Engagement at George Washington University and co-produces the HealthCetera podcast.

Transmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient.

Photo: NIAID via FlickrTransmission electron micrograph of SARS-CoV-2 virus particles, isolated from a patient.

There’s good news for older adults from a new phase2/phase 3 trial of the COVID-19 vaccine under development by Oxford University and AstraZeneca. Researchers found that the partners’ ChAdOx1 nCoV-19 vaccine provides a similar immune response across age groups following a boost dose and appears to be better tolerated in older adults than in younger adults, according to a study published last week in The Lancet.

Because coronavirus vaccine research is on a global fast track, running phase 2 and 3 trials at the same time may be allowed if carefully designed. In the phase 2 component of AstraZeneca’s single-blind, randomized, controlled trial of healthy adults age 18 years and older who were stratified by age and dose group, nearly 100% of participants (ages 18 to >70) developed antibodies against SARS-CoV-2 — including older adults without serious comorbidities. Also, no severe local symptoms were reported by recipients of the experimental vaccine.

The Lancet study was published on Nov. 18. This morning (Nov. 23), AstraZeneca announced interim phase 3 data indicating that ChAdOx1 nCoV-19 overall appeared to reduce the risk of symptomatic Covid-19 by an average of 70.4%, according to the website Stat. The initial headline from The New York Times highlighted a different figure from the announcement, noting that the vaccine appeared to be up to 90% effective under one of the dosing regimens. The announcement is similar to earlier non-peer-reviewed press releases from Pfizer and Moderna about their vaccine candidates, which AHCJ’s Medical Studies Core Topic Leader Tara Haelle has cautioned about.

Getting back to the Lancet study: It’s important to note in your coverage why some vaccines don’t result in a sufficient immune response in older adults. It’s typically due to the gradual aging of the immune system or immunosenescence. The flu vaccine is a good example, with a high dose or adjuvanted version of the standard dose often needed to boost the immune response in people over 65. Immunosenescence is a major reason older adults should be well represented in clinical trials, as I recently discussed.

For the ChAdOx1 nCoV-19 study, investigators recruited 560 generally healthy adults, 18 and older, between May 30 and Aug. 8. Participants were sorted into three age subgroups: 18-55, 56-69, and 70 or older. The study objectives were to assess the safety of immune-provoking response of a single-dose or a two-dose schedule in adults older than 55 years. Participants were randomly assigned to receive either ChAdOx1 nCoV-19 or a control vaccine known as MenACWY, which helps prevent meningococcal disease.

Methods and results

Those receiving ChAdOx1 nCoV-19 were given either a one or two-dose regimen (28 days apart) and received either a low- or standard-dose vaccine. Interestingly, participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. It’s not clear from the study why those administering the vaccines were not blinded as well.

Both low-dose and standard-dose participants showed similar anti-spike antibody titers by day 28 after their prime vaccination. But 28 days after the boost vaccination, similar antibody titers were seen across all two-dose groups, regardless of age or vaccine dose. Also, a clear effect was seen of the boost vaccination on antibody titers at day 56 that was considered unrelated to the dose regimen or age group.

Few serious adverse reactions

Investigators found that local and systemic reactions were more common in those given both the low- and standard-dose ChAdOx1 nCoV-19 than in those given the control vaccine — primarily injection-site pain and tenderness within the first 48 hours after vaccination. Fatigue, headache, feverishness and myalgia were the most commonly reported systemic adverse reactions. Incidence was higher in the 18-55 group than in the 56 to 69 or 70-plus subgroups. In nearly all cases, symptoms were mild to moderate.

Other SARS-CoV-2 vaccine investigations have shown either reduced immunogenicity in an older age group or have not yet been tested in an older population. In the case of Pfizer’s vaccine or Moderna’s vaccine, extensive data has yet to be published.

Phase 3 studies of ChAdOx1 nCoV-19 are ongoing in the U.K., Brazil, and the U.S. to assess vaccine efficacy and safety. If similar safety and immune response in older adults compared with younger adults is confirmed, it could support this vaccine’s use in this older age group.

A reminder: don’t confuse efficacy with effectiveness. This article from The New York Times’ Carl Zimmer does a good job explaining the differences between the terms. As Haelle has reminded me in the past, generating an immune response is not the same as preventing infection or stopping someone from getting COVID-19 or transmitting it to others.

It’s possible that a vaccinated person could contract COVID, not feel sick, but still shed the virus and infect others. The Lancet study only looked at whether the vaccine produced antibodies and how antibodies in older people compared to those in the younger group.

It’s also important to remember that vaccines don’t prevent disease — vaccinations do. So far. This vaccine seems reasonably well tolerated and efficacious across age groups, but its effectiveness is still to be determined.

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