How to improve flu vaccines for older people

In Australia, influenza-associated mortality and hospitalisation rates are highest among older adults aged over 65 years.

It is estimated that each year, flu causes more than 3000 deaths and more than 13,500 hospitalisations among Australians aged over 50 years. Influenza can have a severe and long-term impact on older adults.  

In 2020, measures taken to suppress the Covid-19 pandemic – such as temporary lockdowns, mask-wearing, social distancing, enhanced personal hygiene, reduced travel and increased influenza vaccine uptake – reduced flu cases. This continued into 2021 with almost no influenza notifications seen.

In 2022, however, the lifting of these non-pharmaceutical interventions, coupled with the opening of external borders, led to an early intense influenza season with over 230,000 notifications in Australia, the third highest number on record.

In most years, older adults with flu are four to six times more likely to be hospitalised compared to younger adults. Hospitalisation in older adults due to acute respiratory illness, including influenza, can cause a decline in mobility and function.

Recovery following hospitalisation is also poor in these individuals, with a substantial proportion of older adults not returning to their prior baseline of health and functional status. This decline in mobility and function, and poor recovery following hospitalisation in older adults is associated with greater reliance on community care and increased risk of mortality.

In older adults, avoiding hospitalisation by preventing and managing acute respiratory illnesses (including influenza) is therefore important. 

Vaccination is one of the best defences against influenza.

Vaccinating older adults could reduce hospitalisations from influenza. Annual revaccination is recommended as immunity declines during the year after vaccination, and circulating strains of the influenza virus change from year to year.

When considering flu vaccination for older adults, it is important to note that the antibody response to flu vaccination diminishes with age.

Older adults experience an age-related decline in the immune system known as immunosenescence, impairing their ability to fight natural infections. This can lead to decreased immunogenicity (the ability of an antigen to provoke an immune response in the body) and reduced vaccine effectiveness in older adults. Therefore, vaccines that can address immunosenescence are required to provide adequate protection in older adults. 

Strategies to address immunosenescence for influenza vaccine

High-dose influenza vaccines (i.e., increasing the dose of antigen with the aim of improving antibody response to vaccination).

High-dose influenza vaccines contain three to four times the dose of each of the influenza antigens in comparison with standard-dose vaccines. Several studies have shown that this strategy induces higher antibody response in older adults.

In 2022, a high-dose influenza vaccine was available in Australia only on the private market and primarily for those aged 60 to 64 years. All adults 65 years and over are able to access an adjuvanted influenza vaccine on the National Immunisation Programme (NIP).

Adjuvanted influenza vaccines (i.e., adding agents [adjuvants] to vaccines, with the aim of
improving antibody response to vaccination).

Adjuvanted influenza vaccines contain MF59 adjuvant, an oil-in-water emulsion based on squalene, that acts by stimulating the recruitment of immune cells at the site of injection. This facilitates greater uptake, transportation and processing of the antigens, allowing for improved T-cell priming.

The addition of an adjuvant to influenza vaccine is thought to increase the magnitude of the antibody response based on a statistically significantly higher haemagglutination inhibition (HI) antibody titre against influenza A and B strains for adjuvanted trivalent vaccine recipients than non-adjuvanted vaccine recipients in a systematic review and meta-analysis. However, caution is required in interpreting these results because these HI antibodies have not been correlated with influenza virus protection.

Adjuvanted influenza vaccines are also believed to lead to a broader range of antibodies than standard dose non-adjuvanted vaccines because they were shown to induce higher HI antibody levels to a panel of A/H3N2 influenza strains that were related to, but distinct from the vaccine A/H3N2 strain. This may be important for protection in years when vaccine strains do not match circulating strains, though antibodies to a specific variant of influenza might not protect against either a new variant of the same type or subtype.

The most commonly reported adverse effect was injection site pain, with the majority of events being mild or moderate and resolved within three days.

Co-administration of influenza and Covid vaccines in 2023

In 2023, both flu and Covid-19 vaccinations are important for older adults.

There are no longer any recommendations to separate these two vaccines – they can be given in opposite arms on the same day. Giving both at the same time is “safe” and “does not affect an individual’s immune response to either vaccine”.

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