Past Flu Exposure May Reduce Severity of H5N1 Bird Flu, Study Finds

Using a ferret model, researchers observed that ferrets previously infected with H1N1 flu were protected against severe illness and death when exposed to the H5N1 strain currently spreading among wild birds, poultry, and dairy cows. In contrast, ferrets without prior immunity experienced more severe symptoms and fatal outcomes.

"All human flu pandemics emerge in the context of pre-existing immunity," said lead author Valerie Le Sage, Ph.D., research assistant professor of microbiology and molecular genetics at the University of Pittsburgh. "Our model isn’t perfect because the human immune response is complicated. But if we are using ferrets as surrogates for humans, it is very important to do so in the context of prior immunity."

Despite its high fatality rate in poultry, foxes, mink, and marine mammals, the ongoing H5N1 outbreak in dairy cows has not led to widespread severe disease. The researchers aimed to understand whether prior exposure to flu viruses, particularly H1N1, plays a role in reducing the impact of H5N1 infections.

Ferrets, which closely mimic human flu symptoms, were studied in controlled environments. Among those infected with H5N1, only ferrets that had prior H1N1 immunity survived.

These animals had lower fevers, less weight loss, and faster viral clearance from their nasal passages, limiting the infection to the respiratory tract. In contrast, ferrets with no pre-existing immunity experienced systemic infections, with the virus spreading to the heart, liver, and spleen.

While the study indicates that prior H1N1 infection can reduce disease severity, it does not mean that seasonal flu vaccination against H1N1 will provide similar protection. The researchers noted that antibodies produced against H1N1 do not neutralize H5N1, meaning that prior immunity does not prevent infection but may lessen its impact.

"The study findings suggest that pre-existing immunity against H1N1 from prior infections will not protect someone from getting infected with H5N1, but it can make the infection less severe," said senior author Seema Lakdawala, Ph.D., professor of microbiology and immunology at Emory University’s School of Medicine. "However, young kids whose immune system has not yet been exposed to a lot of viruses, people who are immunocompromised, or those with other underlying health conditions can still get seriously ill."

She added that further studies are needed to determine whether vaccination can provide similar protection, emphasizing that immune responses from infection and vaccination differ.

The study also found that while H1N1-exposed ferrets showed the same level of lung tissue damage as naïve ferrets, they exhibited significantly fewer clinical symptoms, suggesting that the immune response played a role in limiting disease progression.

Moreover, the H5N1 virus in naïve ferrets spread beyond the respiratory tract, affecting the heart, liver, and spleen, whereas in previously infected ferrets, the virus was mostly contained in the lungs and nasal passages.

Despite these findings, the researchers caution that seasonal flu vaccination against H1N1 is unlikely to provide the same level of protection, as antibodies generated from infection and vaccination function differently.

The U.S. Centers for Disease Control and Prevention (CDC) continues to recommend annual flu vaccination to protect against seasonal flu viruses, though there is currently no recommendation for vaccination against H5N1. The study underscores the need for pandemic risk assessments to consider pre-existing immunity when evaluating emerging flu threats.

"Further study into whether vaccination can provide the same level of protection is still needed. Immune responses generated by infection are different from those generated by vaccination," Lakdawala added.

As researchers continue investigating immunity’s role in flu severity, this study highlights the complex relationship between past flu exposure and future disease outcomes, shaping how public health officials approach pandemic preparedness.