A third dose of COVID-19 vaccination triggers vital long-term protection for immunocompromised patients, a new study led by Monash University has found.
Because the immune systems of people with inborn errors of immunity (IEI) don’t function like everyone else’s, it was unclear until now how well COVID-19 vaccinations protected them.
In this Australian-first study, published in the Journal of Allergy and Clinical Immunology, scientists have identified that even IEI patients who usually fail to produce the usual neutralising antibodies used to measure vaccine success benefited from three COVID-19 vaccine doses.
This group had an additional third dose of vaccine included in their primary regimen, compared to the two-dose primary regimen and optional boosters for the rest of the population.
IEI are inherited disorders, otherwise known as primary immunodeficiencies, where the immune system doesn’t work properly, making it harder to fight infections like COVID-19.
Lead author Dr Emily Edwards, Group Leader of the Primary Immunodeficiencies Group at the Monash School of Translational Medicine and Honorary Senior Research Fellow at the Burnet Institute, said the findings offer important hope for people with immune-compromising conditions.
“People who are immunocompromised face up to four times higher risk of hospitalisation and significantly greater risk of severe COVD-19 disease,” Dr Edwards said.
“But because their immune systems don’t work like everyone else’s, it was unclear until now how well COVID-19 vaccines protect them.
“This kind of research is critical to ensure we can deliver the personalised treatment regimes they require to reach immunity levels as close as possible to the rest of the community.”
The study, which examined the immune responses of 25 adults with IEI and compared their COVID-19 vaccination responses to 29 healthy adults, found that IEI patients developed at least one form of adaptive immune memory after vaccination, including antibodies, memory B- or T-cells, both of which are involved in immune functions.
Even among patients who produced no detectable neutralising antibodies, most still generated memory B- or T-cell responses, indicating hidden layers of protection that standard blood tests measuring vaccine responses miss.
Dr Edwards said the study also challenges long-held assumptions about vaccine failure in immunocompromised people, and underscores the importance of tailored vaccination strategies
“We need to look beyond antibody tests alone, to assess vaccine effectiveness,” Dr Edwards said.
“In addition to measuring antibody responses, the traditional gold standard for vaccine efficacy, we also analysed the immune memory, which underpin long-term immune protection and rapid responses to future infections.
“Our research emphasises that vaccine boosters remain critical for people with immune disorders, to increase their lower protection levels.”
The study was led by scientists at Monash University in collaboration with the Burnet Institute, Alfred Hospital, the Monash Medical Centre and other national partners in the PROPHECY consortium (funded by the Medical Research Future Fund) and the JMF Center for Primary Immunodeficiencies in Melbourne.
Read the research paper: https://doi.org/10.1101/2025.11.09.25339598
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