Quantification of heterosubtypic immunity between avian influenza subtypes H3N8 and H4N6 in multiple avian host species

Abstract

Low-pathogenicity avian influenza virus (LPAIV) can lead to epizootics that cause economic losses in poultry or the emergence of human-infectious strains. LPAIVs experience a complex immunity landscape as they are endemic in numerous host species, and many antigenically distinct strains cocirculate. Prevention and control of emergence of detrimental strains requires an understanding of infection/transmission characteristics of the various subtypes in different hosts, including interactions between subtypes. In order to develop analytical frameworks for examining control efficacy, quantification of heterosubtypic immunity interactions is fundamental. However, these data are scarce, especially for wild avian subtypes in natural hosts. Consequently, in this study, three host species (mallards, quail and pheasants) were infected with two LPAIV subtypes isolated from wild birds: H3N8 and H4N6. The recovered hosts were also reinfected with the alternate subtype to measure the effects of heterosubtypic immunity. Oropharyngeal and cloacal swabs were collected and viral RNA load was quantified by real-time RT-PCR. For secondary infections in recovered hosts, peak viral load was up to four orders of magnitude lower and shedding length was up to 4 days shorter. However, both the magnitude and presence of heterosubtypic immunity varied across specific host species/subtype combinations. Using a mathematical model of virus replication, the variation in virus replication dynamics due to host individuals was quantified. It was found that accounting for individual heterogeneity is important for drawing accurate conclusions about treatment effects. These results are relevant for developing epidemiological models to inform control practices and for analysing virus replication data.

Adaptive Heterosubtypic Immunity to Low Pathogenic Avian Influenza Viruses in Experimentally Infected Mallards

“…Our findings are in agreement with previous experimental studies that reported partial cross-protective immunity conferred by primary H3N8 inoculation against H4N6 virus challenge in mallards [20]. Our data also support results from a longitudinal field study where re-infections with phylogenetically related HA subtypes were rare in mallards, and cross-protection between subtypes within the H1 and H3 clades lasted for at least 30 days [21].…”

“…Seasonal patterns of IAV prevalence among wild birds have been described; however, factors and mechanisms that drive diversity and prevalence of IAV subtypes such as the effects of homo- and heterosubtypic immunity remain unclear [14, 15]. Previous studies have demonstrated the induction of homosubtypic and partial heterosubtypic immunity in mallards [16–20], and this has been supported further by field observations [21]. At the same time, additional studies are needed to understand better the effect of reinfections with common and less frequently detected subtypes of LPAIV on the ecology of influenza in the wild bird reservoir.…”

Transmission of H6N2 wild bird-origin influenza A virus among multiple bird species in a stacked-cage setting

“…Therefore, this study clearly showed individual heterogeneity in shedding responses within hosts, similar to what has been observed previously in other species [8]. In addition, the infected mallard in the high-density stack only shed virus for a short duration and aside from a single day, only by the oral route.…”

Long-term variation in influenza A virus prevalence and subtype diversity in migratory mallards in northern Europe

“…B 281: 20140098 strain (homosubtypic immunity) [40,41]. In addition, the development of partial protection against other strains, defined as heterosubtypic or cross-protective immunity, may also occur [40,[42][43][44][45]. This seems to be true for sentinel mallards in nature [46].…”