Efficacy and Safety of COVID-19 Vaccines in Older People

Roy L. Soiza; Chiara Scicluna; Emma C. Thomson

Disclosures

Age Ageing. 2021;50(2):279-283. 

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Genetically Modified Organism (Virus Vector) Vaccines

The vaccines developed by both the University of Oxford/AstraZeneca (ChAdOx1) and Janssen (Ad26.COV2); frequently referred to as the Johnson & Johnson vaccine, particularly in the US media), rely on the genetic modification of adenoviruses that are inactivated due to deletion of the E1 gene, which is replaced with the spike gene. The Janssen Ad26.COV2 vaccine is based on a human adenovirus while the Oxford vaccine is based on a chimpanzee (ChAdOx1) adenovirus, both of which are replication defective. The choice of a chimpanzee adenovirus in the Oxford design was to reduce the impact of human adenovirus antibodies acquired through natural exposure to human adenoviruses over time—a factor likely to be more important in older patients. Spike protein is expressed on the virus particle surface, triggering both antibody and T cell responses that may be protective against COVID-19. Use of genetically modified organisms as vaccines dates back to the early 1980s[6] and has the advantage that the safety of the adenovirus vector at low doses is well established and likely to be transferable to new vaccines, although the vector has never been used in large numbers of older people with frailty. Janssen's phase II trial included just 15 participants aged 65 and over, with rates of adverse events lower (36%) than in younger people (64%).[7] More robust Phase II safety data have been published for the AstraZeneca vaccine, including 200 people aged 70 or over without severe comorbidities or frailty.[8] The vaccine was safe and well tolerated, with neutralising antibodies developing in almost 100% of participants at 28 days follow-up across all age groups. There were no serious or unexpected adverse events and, consistent with the findings for the Janssen study, the incidence of mild and moderate severity adverse events in the immediate post-vaccination period was lower in the older age groups. Both the AstraZeneca and Janssen vaccines are currently undergoing Phase III testing in the UK as part of international trials. Early results from the AstraZeneca vaccine suggested the vaccine averaged 70% efficacy overall. Of note, adenovirus vectored vaccines have also been developed and tested in China (Cansino Biological) and Russia (Gamileya Research Institute). Cansino's vaccine elicited neutralising antibody and T-cell mediated responses in a dose-dependent manner with lower levels in those aged over 55. Gamileya reported in a press release its Sputnik vaccine was 92% effective, but this analysis was based on only 20 positive cases and no age breakdown for the trial has been provided to date.

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