Could your previous infection against the flu protect you from the bird flu? Scientists find that immunity to 2009 H1N1 reduces the risk of serious H5N1 disease, even after close exposure.
Study: preexisting immunity of the H1N1 2009 pandemic virus reduces sensitivity to infection and H5N1 disease in ferrets. Image credit: Digicomphoto / Shutterstock
In a recent study published in the journal Translational scientific medicineA group of researchers has tested if the immunity caused by influenza Infections A Virus (IAV) Hemagglutinine 1 Neuraminidase 1 (H1N1) or Hemaggglutinine 3 Neuraminidase 2 (H3N2) (H5N1), including after direct contact with a dairy cow isolate.
Background
At the age of five, most people have already met the IAV, leaving an immune imprint that shapes their responses to subsequent exposures. Since 2020, the CLADE 2.3.4.4B H5N1 has swept the birds and has spread in mammals, including an unprecedented epidemic in dairy cows in the United States, affecting 989 herds in 17 states within a year and 41 infections confirmed by the laboratory among agricultural workers by June 2025.
Most human cases have been light, which aroused a key question: can the preexistence of immunity with seasonal strains blunt H5N1 disease? Understanding the answer is important for workers, clinicians and pandemic planners.
Additional research is necessary to clarify how printing and reactive cross antibodies support protection over time.
About the study
The researchers used a well -established ferret model because the ferrets summarize the key characteristics of pathogenesis and the transmission of human flu. They first induced preexisting immunity by infecting animals with the B / Brisbane / 60/2008 virus, the influenza B virus (IBV), A / PERTH / 16/2009 H3N2 IAV, or A / California / 07/2009 2009 H1N1 IAV.
In a separate experience, the ferrets received two sequential infections, 90 days apart, to test the effect of the imprint. Ninety days after the last seasonal infection, the animals were attractive intranasially with an infectious dose of tissue culture of 10% (TCID₅₀) of an H5N1 A / MINK / Spain / 2022 virus / 2022 very pathogenic or a pair hosted with a naive cage companion which had been inoculated with 10½ H5N1 to contact the model A / Dairy Actle / Texas / Texas / 2024 H5N1 Virus.
The nasal washes were collected every two days and titled on kids kidney cells from Madin-Darby; Body weight, clinical scores and survival have been monitored. The serum liaison antibodies of immunoglobulin G (IGG), neutralization and neuraminidase have been quantified by immuno-enzymatic trial (Elisa), microneutalization and lectin test linked to Enzyme (ELLA), respectively.
The predetermined human evaluation criteria have triggered euthanasia. Four ferrets were used by group; The experiences have not been randomized or blind. Statistical comparisons used variance analysis or non -parametric tests, if necessary, and survival was analyzed using the Cox Mantel test in the prism.
Study results
Pre -existing immunity imported, compared to immunologically naive or preimmune IBV ferrets, animals previously infected with the 2009 H1N1 Pandemic H1N1 IAV have significantly fewer viruses after a challenge with the A / MINK / Spain / 2022 H5N1 strain, maintained body weight, has not shown any clinical disease, and all survived.
H3N2 IAV seasonal immunity offered partial protection: the viral titles were intermediate, some animals lost significant weight, but all survived. Only pre-immune ferrets H1N1 have set up robust IGG responses to H1N1, and these antibodies neutralized H1N1 and inhibited the activity of the Neuraminidase of H5N1; They also showed a low and non -neutralizing cross -reactivity at H5 Hémagglutinin.
When the team overlapped infections to probe the immune footprint, the model maintains. It does not matter that H1N1 came first or second, any group which included the H1N1 2009 virus lost minimal or no H5N1 and has not developed a disease. On the other hand, the ferrets which have experienced two cycles of IBV infection, or the H3N2 sequence followed by IBV, lost high titles, lost at least 15% of body weight and up to half of the human evaluation criteria. Thus, the order counted less than the simple H1N1 in the history of infection.
Finally, in a direct contact experience modeling the high dose exhibitions observed during the dairy milking, the ferrets of naive donors infected with a H5N1 strain of dairy cow have transmitted the virus to 100% of naive cage companions, causing a universally lethal disease. Anterior H3N2 immunity did not prevent infection; Each contact virus is redirecting and half survived. The anterior H1N1 immunity considerably increased the bar: only half of the contacts had a low transitional loss in a single day, none has developed a clinical disease and all survived.
Together, these data show that immunity caused by infection to the H1N1 2009 virus reduces sensitivity, replication and disease caused by contemporary clade 2.3.4.4.4B H5N1 viruses in ferrets, while H3N2 immunity alone gives incomplete and variable protection.
Mechanically, exposure to H1N1 generated high reactive Neuraminidase N1 binding antibodies that inhibited H5N1 neuraminidases from the dairy cow and mink, plus low titles in group 1 of antibodies led by hemagglutinin which are not neutralized H5. Nucleoprotein antibodies, an indirect indicator of the responses to internal preserved antigens, were comparable between the H1N1 and H3N2 groups, which suggests that higher protection in reprimanded H1N1 animals probably reflected hemagglutinin or the cross -reactivity of neuraminidase rather than broader immunity to internal proteins. These immunological patterns reflect recent human serology against clade 2.3.4.4b H5N1, reported in independent studies.
Conclusions
To summarize the immunity, preexisting and elicited by the infection of the 2009 pandemic, H1N1 IAV acted as a strong barrier against clade 2.3.4.4b H5N1, replication and disease in ferrets, even after exposure to direct contact in high doses. IAV seasonal H3N2 immunity has attenuated but has not reliably prevented infection or disease. The order of previous infections (imprint) has not eroded the protection conferred by exposure to H1N1.
Although the authors recognize certain limits, such as infection intervals at 90 fixed days not reflecting human deadlines and the inability to assess cellular immunity, these results help to explain why the most recent H5N1 infections linked to dairy cows have been light and have affirmed that strategies of conception of vaccination, risk assessment and clinical policies and clinical policies and risks risk assessment.
