Biology subjects

Hurt, A.

Publications and source records attributed to Hurt, A..

5 recordsLinked to original sources

bioRxiv2025

Memory T and B cells with recognition of avian influenza hemagglutinins are poorly responsive to existing seasonal influenza vaccines

Immunisation remains the most cost-effective mechanism to combat global influenza infection and is widely employed against seasonal influenza viruses. Zoonotic transmission of avian influenza A viruses represents a significant threat to human health given the lack of population level immunity, which could translate into an influenza pandemic. Therefore, there is a need to better understand pre-existing human immunity against avian influenza strains. as highlighted by the recent rapid, global spread of avian H5Nx clade 2.3.4.4b variants. Here, we sought to quantify the frequencies and specificities of B cells recognising avian hemagglutinin (HA) within unexposed adults, and to characterise the ability of seasonal immunisation to boost cross-reactive immune responses to H5Nx strains, including from clade 2.3.4.4b. Low but detectable serum antibody titres against H5 and H7 avian influenza HA were observed in donors. The frequency of memory B cells with cross-reactive recognition of H5 and H7 HA was low and 2-5 fold lower than populations of seasonal H1N1 and H3N2 HA-specific B cells. Boosting of B cell responses against H5Nx clade 2.3.4.4b HA following seasonal immunisation were sporadic with only 3 out of 19 individuals showing an increased population of probe-positive cells. Cross-reactive B cells generally expressed immunoglobulins drawn from variable heavy chain genes associated with recognition of the HA stem (VH6-1, VH1-69, VH1-18). CD4+ T cell responses towards H5 HA were also weakly boosted with little to no increase in circulating T follicular helper cell populations. These findings highlight the need for avian influenza-specific vaccine products to bolster immunity in human populations, with consideration for use in pre-pandemic preparedness to expand baseline frequencies of avian influenza-specific memory B and T lymphocytes.

immunology↗

bioRxiv2019

Sustained virome diversity in Antarctic penguins and their ticks: geographical connectedness and no evidence for low pathogen pressure

Despite its isolation and extreme climate, Antarctica is home to diverse fauna and associated microorganisms. It has been proposed that the most iconic Antarctic animal, the penguin, experiences low pathogen pressure, accounting for their disease susceptibility in foreign environments. However, there is a limited understanding of virome diversity in Antarctic species, the extent of in situ virus evolution, or how it relates to that in other geographic regions. To test the idea that penguins have limited microbial diversity we determined the viromes of three species of penguins and their ticks sampled on the Antarctic peninsula. Using total RNA-Sequencing we identified 107 viral species, comprising likely penguin associated viruses (n = 13), penguin diet and microbiome associated viruses (n = 82) and tick viruses (n = 8), two of which may have the potential to infect penguins. Notably, the level of virome diversity revealed in penguins is comparable to that seen in Australian waterbirds, including many of the same viral families. These data therefore reject the theory that penguins are subject to lower pathogen pressure. The repeated detection of specific viruses in Antarctic penguins also suggests that rather than being simply spill-over hosts, these animals may act as key virus reservoirs.

microbiology↗

bioRxiv2019

Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin

A longstanding question is how influenza evolves to escape human immunity, which is polyclonal and can target many distinct epitopes on the virus. Here we map how all amino-acid mutations to influenzas major surface protein affect viral neutralization by polyclonal human sera. The serum of some individuals is so focused that it selects single mutations that reduce viral neutralization by over an order of magnitude. However, different viral mutations escape the sera of different individuals. This individual-to-individual variation in viral escape mutations is not present among ferrets, which are frequently used as a model in influenza studies. Our results show how different single mutations help influenza escape the immunity of different members of the human population, a phenomenon that could shape viral evolution and disease susceptibility.

microbiology↗

bioRxiv2019

Virome heterogeneity and connectivity in waterfowl and shorebird communities

Models of host-microbe dynamics typically assume a single-host population infected by a single pathogen. In reality, many hosts form multi-species aggregations and may be infected with an assemblage of pathogens. We used a meta-transcriptomic approach to characterize the viromes of nine avian species in the Anseriformes (ducks) and Charadriiformes (shorebirds). This revealed the presence of 27 viral species, of which 24 were novel, including double-stranded RNA viruses (Picobirnaviridae and Reoviridae), single-stranded RNA viruses (Astroviridae, Caliciviridae, Picornaviridae), a retro-transcribing DNA virus (Hepadnaviridae), and a single-stranded DNA virus (Parvoviridae). These viruses comprise multi-host generalist viruses and those that are host-specific, indicative of both virome connectivity and heterogeneity. Virome connectivity was apparent in two well described multi-host virus species (avian coronavirus and influenza A virus) and a novel Rotavirus species that were shared among some Anseriform species, while heterogeneity was reflected in the absence of viruses shared between Anseriformes and Charadriiformes. Notably, within avian host families there was no significant relationship between either host taxonomy or foraging ecology and virome composition, although Anseriform species positive for influenza A virus harboured more additional viruses than those negative for influenza virus. Overall, we demonstrate complex virome structures across host species that co-exist in multi-species aggregations.

ecology↗

bioRxiv2018

Baloxavir Marboxil Susceptibility of Influenza Viruses from the Asia-Pacific, 2012-2018.

Baloxavir Marboxil (BXM) is an influenza polymerase inhibitor antiviral that binds to the endonuclease region in the PA subunit of influenza A and B viruses. To establish the baseline susceptibility of viruses circulating prior to licensure of BXM and to monitor for susceptibility post-BXM use, a cell culture-based focus reduction assay was developed to determine the susceptibility of 286 circulating seasonal influenza viruses, A(H1N1)pdm09, A(H3N2), B (Yamagata/Victoria) lineage viruses, including neuraminidase inhibitor (NAI) resistant viruses, to Baloxavir Acid (BXA), the active metabolic form of BXM. BXA was effective against all influenza subtypes tested with mean EC50 values (minimum-maximum) of 0.7 {+/-} 0.5 nM (0.1-2.1 nM), 1.2 {+/-} 0.6 nM (0.1-2.4), 7.2 {+/-} 3.5 nM (0.7-14.8), and 5.8 {+/-} 4.5 nM (1.8-15.5) obtained for A(H1N1)pdm09, A(H3N2), B(Victoria lineage), and B(Yamagata lineage) influenza viruses, respectively. Using reverse genetics, amino acid substitutions known to alter BXA susceptibility were introduced into the PA protein resulting in EC50 fold change increases that ranged from 2 to 65. Our study demonstrates that currently circulating viruses are susceptible to BXA and that the newly developed focus reduction assay is well suited to susceptibility monitoring in reference laboratories.

microbiology↗