H5N1 Establishes Productive Infection in Alpacas After Intranasal Challenge
A controlled challenge study shows HPAI H5N1 clade 2.3.4.4b can infect alpacas and replicate beyond a purely incidental exposure event. In six healthy male alpacas, intranasal inoculation with genotype B3.13 produced mild clinical illness, detectable nasal shedding, and evidence of localized tissue infection in the upper respiratory tract. The findings matter because camelids had already surfaced in field reports as naturally infected hosts, yet their true susceptibility and tissue tropism were still uncertain.
The illness pattern was subtle rather than dramatic. Body temperature rose slightly, and food intake fell for up to 3 days after infection. Even so, viral RNA appeared in nasal swabs, infectious virus was recovered, and histologic methods confirmed virus in the nasopharyngeal tonsil and nasal conchae at 4 days postinfection. In a host species that can look clinically quiet while carrying a replicating avian influenza virus, mild signs do not equal biologic triviality.
Upper Airway Replication Dominated the Early Phase
Investigators used six alpacas, 12 to 24 months old, housed in two groups before intranasal inoculation with genotype B3.13 virus isolate A/Cattle/Texas/063224-24-1/2024. The viral dose was delivered to each nostril by nebulizer. Animals were monitored daily, and nasal and rectal swabs were collected repeatedly after inoculation, while subsets were euthanized at 4 days and 20 days postinfection to map organ distribution and serologic response.
The biologic signal concentrated in the nose rather than the lower respiratory tract or internal organs. Viral RNA and infectious virus were found in nasal swabs, and tissue assays localized infection to the nasopharyngeal tonsil and nasal conchae at 4 days postinfection. No comparable spread to the trachea, lungs, liver, kidney, or spleen is described in the core findings. In influenza biology, that pattern suggests the virus can establish a productive foothold in mucosal epithelium without necessarily driving immediately systemic disease in this host.
The route of infection is clinically relevant. Intranasal exposure approximates the kind of mucosal contamination that could occur in a contaminated farm environment, especially where shared water, feed, or respiratory secretions create repeated contact between species. Upper airway localization also helps explain why an infected animal can remain only mildly ill while still contributing to environmental contamination and potential onward spread.
Field Outbreak Clues Matched the Experimental Signal
The experimental work follows a 2024 farm outbreak in which alpacas shared pasture and water with infected poultry and ducks. On that premises, H5N1 was confirmed in alpacas carrying the same B3.13 genotype identified in infected poultry and dairy cattle. Only female alpacas were clinically affected in the field event, and several abortions occurred, including one fetus later found to have H5N1 in brain tissue. Ten surviving female alpacas seroconverted, and viral genome was also detected in alpaca milk, pointing to acute infection of the udder.
Those field observations made the species question impossible to ignore. Alpacas are not obvious sentinel animals for influenza surveillance, yet the natural outbreak showed they could be infected under real-world exposure pressure. The experimental study now closes part of that gap by demonstrating that productive infection is not a one-off anomaly tied only to a contaminated farm. The virus can replicate in alpacas after direct inoculation, and the upper airway appears to be a plausible primary site of early replication.
Serology Confirmed Host Response After Infection
Serologic testing was built into the study design with two H5 antibody assays, including an in-house clade 2.3.4.4b-adapted H5 nanoluciferase-based ELISA and a commercial H5 antibody competition assay. Those tests were used to track whether infected alpacas mounted an immune response after challenge. The presence of serologic conversion supports the conclusion that the animals did not merely carry input virus transiently in the nose; they developed evidence of host recognition after infection.
That matters for two reasons. First, it confirms biological exposure at a level sufficient to trigger adaptive immunity. Second, it helps distinguish true infection from surface contamination, which is a constant issue in high-exposure livestock settings. A serologic response after challenge strengthens the inference that alpacas can support the full sequence of infection, replication, and immune activation.
Why Camelid Susceptibility Matters for Surveillance
The broader context is the continuing expansion of clade 2.3.4.4b across birds and mammals. Since its spread from Europe to North America in 2021, the virus has diversified through reassortment and has been detected in wild birds, domestic poultry, dairy cattle, goats, domestic cats, rodents, and other mammals. Human infections have also occurred in the United States, most often linked to infected dairy cattle or poultry, with conjunctivitis, fever, and respiratory symptoms reported in a substantial fraction of cases.
Against that backdrop, alpacas are not just another incidental host. They are livestock animals with close human contact, farm-to-farm movement, and the capacity to share space with other susceptible species. A mammalian host that can be infected productively, shed virus from the upper airway, and seroconvert becomes relevant to on-farm biosecurity in a way that extends beyond species curiosity. In practical terms, camelid surveillance should not be dismissed when H5N1 is moving through mixed-animal operations.
The study also indicates how much of influenza pathogenesis is still governed by tissue entry and local replication kinetics rather than dramatic systemic disease. In this case, the virus established itself where inhaled pathogens usually begin, in the mucosa of the upper respiratory tract. That pattern is consistent with the idea that host range expansion may begin with limited, anatomically constrained replication before broader adaptation emerges.
What the Alpaca Model Adds to H5N1 Risk Assessment
The core result is straightforward: alpacas are susceptible to H5N1 infection, and the virus can produce infectious shedding and localized upper airway infection after nasal exposure. The illness was mild, but mild disease does not eliminate transmission risk, especially in settings where many animals share air, feed, and water. The detection of virus only in the nasopharyngeal tonsil and nasal conchae at 4 days postinfection suggests early mucosal tropism rather than extensive visceral dissemination.
Because the study used only six animals and focused on a single genotype, it cannot define the full clinical spectrum across ages, sexes, exposure routes, or viral lineages. It also does not establish whether alpacas can transmit efficiently to other animals. Those questions remain open and deserve follow-up challenge and field studies, especially as clade 2.3.4.4b continues to evolve in livestock and wildlife.