Prior Immunity to the 2009 H1N1 Pandemic Virus Protects Against Lethal Cattle H5N1 Virus Infection in Ferrets

Figure 1. Role of prior H1N1 immunity on mortality and replication of cattle H5N1 in ferrets. Two groups of ferrets were infected with A/dairy cattle/Texas/24008749001/2024; group 1 had been infected with A/CA/07/09 H1N1pdm09 98 days priors (n=5) and group 2 were immunologically naïve (n=5). A) Study schematic B) Mortality of ferrets in each group (n=2 per group) C) Clinical signs on various days, n=5 on days 1-3 and n=2 on days 4 until end of the study D) Nasal wash titers in both groups E) Viral load in the ferret tissues within the animals.

University of Pennsylvania CEIRR (Penn-CEIRR) researchers at the Center for Vaccine Research at the University of Pittsburgh Valerie Le Sage, Ph.D. and Seema Lakdawala, Ph.D., along with collaborators studying the lethal bovine H5N1 outbreak found that prior immunity to the virus protected against the disease in ferrets.

Goal: Human infections of the cattle H5N1 virus occur in the presence of prior human seasonal immunity. However, the replication and pathogenesis of the virus in animal models is done in the absence of prior influenza immunity.

Approach: To address this gap, ferrets with or without prior H1N1pdm09 immunity were intranasally inoculated with the dairy cattle H5N1 virus (clade 2.3.4.4b) at a dose of 10⁴ TCID₅₀/mL and sacrificed on day 3 (n=3) for assessment of viral load (Figure 1a). Two additional animals were followed out to day 14 to examine mortality.

Results: All animals with prior H1N1 immunity survived challenge with the lethal H5N1 virus (Figure 1b). Assessment of clinical signs such as weight loss and playfulness revealed very modest clinical signs in all five animals with prior immunity compared to those that were immunologically naive (Figure 1c). Viral load in the nasal washes for all animals (n=5 days 1-3; n=2 days 4-8) was significantly lower in H1N1-immune ferrets compared to animals without prior immunity (Figure 1d). Infection with cattle H5N1 produced a systemic infection in ferrets without prior immunity as observed with virus detection in the liver, heart, spleen, and intestine (Figure 1e). However, only respiratory infection was observed in ferrets with prior H1N1 immunity (Figure 1e).

Conclusion: Taken together, these data suggest that immunity with prior human seasonal viruses can reduce the severity of disease from the highly pathogenic avian influenza (HPAI) cattle H5N1 virus and may explain why the human cases have been less severe during the current outbreak.

This article is part of a manuscript that was submitted for publication but has not been certified by peer review. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.