Most of us assume that once you're vaccinated against something, you're protected. A recent case report is a reminder that it's not always that simple.
A 72 year old man in the Netherlands developed acute Hepatitis B despite being fully vaccinated and despite having a strong antibody response after vaccination. What makes this case particularly striking is that his immunity was well documented. He had received all three doses of the Hepatitis B vaccine back in 2003, and his antibody levels were well above the protective threshold at the time. Even when he fell ill, his antibodies were still detectable.
So how did the virus get through?
The answer lies in a mutation. Genomic testing identified a specific change in the virus called the D144A mutation in a region of the Hepatitis B surface antigen that vaccine induced antibodies are designed to target. Essentially, the virus had mutated just enough that the antibodies couldn't recognise and neutralise it effectively. This is what doctors call "vaccine escape."
The patient had no obvious risk factors - no new sexual contacts, no blood transfusions, no tattoos or other blood exposure. The infection appeared to come out of nowhere.
What were the symptoms?
Interestingly, the man initially came in with what seemed like heartburn. But a clinical examination revealed an enlarged liver, and blood tests told a different story severely elevated liver enzymes, high bilirubin, and Hepatitis B virus DNA detected in his blood, all pointing to acute Hepatitis B infection.
The good news
He recovered on his own without any treatment. Within days, the virus levels in his blood began dropping, and by three months, his liver tests and surface antigen levels had fully normalised. Doctors noted that his vaccination may actually have prevented the infection from becoming chronic which is the more dangerous, long-term form of the disease.
How rare is this?
Quite rare, but worth tracking. Dutch surveillance data spanning 2004 to 2024 looked at over 2,400 sequenced Hepatitis B samples and found that vaccine escape variants accounted for just 3.5% of cases. The specific D144A mutation was found in only four other strains over the entire 20-year period.
What this means for doctors and patients?
The key takeaway from this case is that Hepatitis B should not be automatically ruled out just because a patient is vaccinated. Vaccine escape is uncommon, but it does happen. Doctors are being urged to keep HBV in mind when a vaccinated patient presents with unexplained liver symptoms and researchers are calling for continued genomic surveillance to catch any emerging strains before they become a wider concern.
