A genetically engineered therapeutic #lectin inhibits #human #influenza A virus #infection and sustains robust virus-specific #CD8 T cell expansion

Abstract

Seasonal influenza continues to be a global health problem. Current existing vaccines and antivirals against influenza have limited effectiveness, and typically do not stay ahead of the viral evolutionary curve. Broad-spectrum antiviral agents that are effective therapeutically and prophylactically are much needed. We have created a promising new broad-spectrum anti-influenza agent using molecular engineering of a lectin from bananas, H84T, which is well-tolerated and protective in small animal models. However, the potency and effect of H84T on human immune cells and influenza-specific immune responses are undetermined. We found that H84T efficiently inhibited influenza A virus (IAV) replication in primary human dendritic cells (DCs) isolated from blood and tonsil, preserved DC viability and allowed acquisition and presentation of viral antigen. Excitingly, H84T-treated DCs subsequently initiated effective expansion of IAV-specific CD8 T cells. Furthermore, H84T preserved the capacity of IAV-exposed DCs to present a second non-IAV antigen and induce robust antigen-specific CD8 T cell expansion. Our data support H84T as a potent antiviral in humans as it not only effectively inhibits IAV infection, but also preserves induction of robust pathogen-specific adaptive immune responses against diverse antigens, which likely is clinically beneficial.

Abstract

Influenza causes large-scale, global morbidity and mortality. Current antiviral treatments and vaccines have significant limitations, especially when dealing with evolving strains of the virus. Banana lectin (BanLec) has broad antiviral effects on enveloped viruses, including influenza, but also causes harmful T cell proliferation and inflammation (mitogenicity). We previously used targeted molecular engineering to produce H84T BanLec (H84T), which is effective against all isolates of influenza tested and is not mitogenic. However, the effect of H84T on the human immune response to influenza had not been ascertained. Here we assessed the effect of H84T on human dendritic (antigen-presenting) cells and virus-specific T cell immune responses against influenza infection and unrelated antigen. We found that H84T treatment allowed dendritic cells to maintain their function during viral infection. H84T prevented the damage caused by viral replication and preserved the ability of dendritic cells to present not only influenza but also secondary, non-influenza antigens to T cells. Thus, H84T could be a valuable tool for controlling influenza infection and potentially preserving responses to secondary infections, which are common and often deadly in influenza patients. H84T holds promise as a novel antiviral that combines control of viral replication with enhancement of the immune response.

Source: PLoS Pathogens, https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013112

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