Since early 2020, the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has impacted population health around the world. Coronavirus disease 2019 (COVID-19) caused by the virus is particularly severe in older individuals because they are more likely to have an impaired immune response1. Older adults have benefitted the most, in terms of reduced morbidity and mortality, from vaccination. At the same time, the vaccines rolled out so far are less efficacious in older individuals2. Writing in Nature Microbiology, Newman et al.3 report that they have analysed the neutralizing antibodies against SARS-CoV-2 and its variants in 70–89 year old adults vaccinated with BNT162b2 (Pfizer–BioNTech). They report that immunity to wild-type SARS-CoV-2 decreases between 3 and 20 weeks after the second dose, but a third booster dose increases antibody titres and provides cross-protection against Omicron BA.1 and BA.2 (Fig. 1).

Immune function declines with age in a process called immunosenescence1,2. Both the innate and the adaptive immune system show reduced function of natural killer cells and dendritic cells and reduced diversity and memory of T and B cells2. As a result, several infectious diseases have high morbidity and mortality in the older population. The top three diseases, except for COVID-19, that are preventable by vaccination are influenza, herpes zoster and pneumococcal disease2. Incidence rates of these diseases increase rapidly after the age of 65 years, with another fivefold increase after the age of 85 (ref. 2). Older adults may hence benefit the most from vaccinations. To further enhance the immune response in older individuals, higher doses of vaccines have been suggested2. There are several COVID-19 vaccines available, many of which have a reported efficacy above 90% in adults (>18 years)4. However, thus far, no age-specific recommendations other than additional booster doses have been recommended.

Fig. 1: Immunity against SARS-CoV-2 in the older population.
figure 1

SARS-CoV-2 vaccine–induced humoral immune responses wane over time and are generally reduced in older (80 to 89 years) as compared with younger (70 to 79 years) people. To maintain protection against emerging variants, booster vaccination is required to maximize antibody defences. The x axis shows time in months when designated variants of concern (VOCs) were dated and the approximate times for vaccinations of the older population, indicated with the syringes. The y axis shows the schematic level of immune response.

Newman et al.3 used a SARS-CoV-2 spike pseudotype–based microvirus neutralization assay to determine neutralizing titres in 37 older individuals from the United Kingdom. Participants were sampled two times after the second dose and a third time after a third dose, allowing for longitudinal follow up of immune function. They tested neutralization against several VOCs, including mutational profiles of B.1, Alpha, Beta, Delta, Theta and Omicron, and highlighted antigenically divergent variants (for example, C.1.2 and B.1.638). The antibody response for Beta and Omicron was lower than that for other variants, but immunity was rescued after a third dose when all sample titres were above detection level. Antibody levels in the 70–79-years-old group were generally higher across all assays as compared with the 80–89-years-old group, highlighting the age-related decline in immunity.

The study by Newman et al.3 confirmed the results presented earlier in Nature Microbiolgy by Romero-Olmedo et al.5. In their study, Romero-Olmedo and colleagues showed that older individuals (age range 80–97 years) have lower neutralizing titres against SARS-CoV-2 than younger individuals (age range 20–53 years) after one or two doses of BNT162b2. Some of the older individuals were low responders or non-responders and had antibody titres below the detection level, but were able to mount an antibody and T-cell immune response after a third dose. The reasons for being low responders or non-responders were investigated but remained unclear and could not be attributed to age, comorbidity or overall low immunity. Although the Romero-Olmedo study did not test as many SARS-CoV-2 variants as the Newman study, they also showed protection against the Delta variant, suggesting immunity across several VOCs with BNT162b2. It is clear that new variants will continue to emerge, warranting further booster shots.

For continued safe and efficacious vaccination of older adults, it is important to keep monitoring the spread of SARS-CoV-2 and its variants and to update health policies as our knowledge improves. Currently, other vaccines, such as protein-based vaccines, against SARS-CoV-2 are being tested. Results from a phase 1 clinical trial show higher and longer-lasting T-cell response than that induced by messenger RNA vaccines or natural immunity, even in older adults6. Moreover, different modes of vaccinations are studied, for example, needle-free approaches such as aerosol delivery of COVID-19 vaccines, which are safe and painless7. Ways to enhance the vaccine-induced immune response in older people could also hold promise1. A clinical trial showed a 20% induced antibody titre response after influenza vaccination in rapamycin-treated 65 year olds when compared with placebo8.

In summary, the article by Newman et al.1 provides additional needed evidence of vaccine-induced SARS-CoV-2 immunity in the oldest adults in the population. The authors present a comprehensive analysis of all the main mutations of the virus, including those in Omicron, and the neutralizing antibody responses to them. The focus on older adults is welcome because, while this group have borne the brunt of illness and lives lost, studies on older adults have so far been few in number. One limitation of both studies is that the results are based on only one mRNA vaccine (Pfizer–BioNTech). The study provides valuable insights into vaccine-induced immunity in the vulnerable group of older adults that will inform clinicians and public health authorities. However, more research is needed in older adults to characterize the immunity provided by different SARS-CoV-2 vaccines, including those with different routes of administration. Future studies may also be needed to provide evidence of strategies other than boosters, including potentiation of the immune response, to increase COVID-19 protection in older adults.