Why do some people develop better protection after vaccination than others?

Genetic predisposition is the most important explanation for the variation in how well people respond to vaccines. The so-called HLA system, the set of proteins your body uses to recognise vaccine substances and present them to the immune system, differs from person to person. Certain variants of this system are associated with a weaker response. This means some people are naturally less amenable to protection through vaccination, regardless of which vaccine is used.

The state of your immune system just before vaccination also plays a role. Research into the BCG vaccine showed that people with a relatively quiet immune system benefited more from it than people whose system was already active. Genetic and environmental influences on which genes are switched on or off predicted that difference. Universally benefiting from a vaccine is therefore not a given: the starting position matters.

Age is a third factor. Older people respond on average less strongly to vaccines than younger adults, and they also vary much more among themselves. This makes it harder to give standard recommendations: group averages mask the fact that one person at an advanced age still responds well while another barely responds at all.

Certain diseases and medications substantially suppress the vaccine response. People with multiple sclerosis who use rituximab or fingolimod produced far fewer antibodies after COVID-19 vaccination than MS patients on other medications. Coeliac disease is also associated with a poorer antibody response to the hepatitis B vaccine, while the response to other vaccines in children with this condition largely remains comparable to that of healthy children. COPD likewise leads to a less reliable flu vaccine effect, although the evidence for this is more limited.

On the positive side: people who had previously had COVID-19 and were subsequently vaccinated responded more strongly than those who had only been vaccinated. This so-called hybrid immunity produced higher antibody levels and stronger T-cell responses. Vaccines containing adjuvants, substances that additionally activate the immune system, can also boost the response in people with a less favourable predisposition, although individual differences remain.