Biology subjects

Schwab, L. S. U.

Publications and source records attributed to Schwab, L. S. U..

3 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↗

bioRxiv2023

Dissemination of influenza B virus to the lower respiratory tract of mice is restricted by the interferon response

The global burden of disease caused by Influenza B virus (IBV) is substantial, however IBVs remain overlooked. Understanding host-pathogen interactions as well as establishing physiologically relevant models of infection are important for the development and assessment of therapeutics and vaccines against IBV. Here, we assessed an upper respiratory tract (URT)-restricted model of mouse IBV infection, comparing it to the conventional administration of virus to the total respiratory tract (TRT). We found that URT infections with different strains of IBV resulted in limited dissemination of IBV to the lungs. Infection of the URT did not result in weight loss or systemic inflammation even at high inoculum doses and despite robust viral replication in the nose. Dissemination of IBV to the lung was enhanced in mice lacking functional type I IFN receptor (IFNAR2) but not IFN{gamma}. Conversely, in mice expressing the IFN-inducible gene Mx1 we found reduced IBV replication in the lung and reduced dissemination of IBV from the URT to the lung. Both URT and TRT inoculation with IBV resulted in seroconversion against IBV. However, priming at the TRT conferred superior protection from a heterologous lethal IBV challenge compared to URT priming, as determined by improved survival rates and reduced viral replication throughout the respiratory tract. Overall, our study establishes a URT-restricted IBV infection model, highlights the critical role of IFNs in limiting dissemination of IBV to the lungs but also demonstrates that the lack of viral replication in the lung may impact protection from subsequent infections. ImportanceOur study investigated how IBV spreads from the nose to the lung of mice, the impact this has on disease and protection from re-infection. We found that when applied to the nose only, IBV does not spread very efficiently to the lungs in a process controlled by the interferon response. Priming immunity at the nose only was less protective from re-infection than priming immunity at both the nose and lung. These insights can guide the development of potential therapies targeting the interferon response as well as of intranasal vaccines against IBV.

immunology↗

bioRxiv2023

Differential cross-reactivity to the influenza B virus haemagglutinin underpins lineage-specific susceptibility between birth cohorts

Influenza exposures early in life are believed to shape future susceptibility to influenza infections by imprinting immunological biases that engender differential cross-reactivity to future influenza viruses, but direct serological evidence linked to susceptibility is limited. We analysed hemagglutination-inhibition titres in 1451 cross-sectional samples collected between 1992-2020, from individuals born between 1917-2008, against influenza B virus (IBV) isolates from 1940-2021, including future isolates that circulated after sample collection. We demonstrate that immunological biases are conferred by early life IBV infection and result in lineage-specific cross-reactivity of a birth cohort towards future IBV isolates. This translates into differential estimates of susceptibility between birth cohorts towards the two IBV antigenic lineages, explaining lineage-specific age distributions of observed medically attended IBV infections. Our data bridge a critical gap between early life exposure, cross-reactivity, and influenza epidemiology and identify a plausible model to further dissect the interplay between host immunity, viral evolution and epidemiology.

immunology↗