Lebens, M. | bioRxiv Science

bioRxiv2024

Influenza A Virus H7 nanobody recognizes a conserved immunodominant epitope on hemagglutinin head and confers heterosubtypic protection

Influenza remains a persistent global health challenge, largely due to the virus continuous antigenic drift and shift, which impede the development of a universal vaccine. To address this, the identification of broadly neutralizing antibodies and their epitopes is crucial. Nanobodies, with their unique characteristics and binding capacity, offer a promising avenue to identify such epitopes. Here, we isolated and purified a hemagglutinin (HA)-specific nanobody that recognizes an H7 subtype of influenza A virus. Notably, the nanobody, named E10, exhibited broad-spectrum binding, cross-group neutralization and in vivo protection across various influenza A subtypes. Through phage display and in vitro characterization, we demonstrated that E10 specifically targets an epitope on HA head. This epitope is part of the conserved lateral patch of HA head and proved to be highly immunodominant upon H7 infection. Importantly, immunization with a peptide including the E10 epitope elicited cross-reactive antibodies and mediated partial protection from lethal viral challenge. Our data highlight the potential of E10 and its associated epitope as a candidate for future influenza prevention strategies.

microbiology↗

bioRxiv2020

Serotype has a significant impact on the virulence of 7th pandemic Vibrio cholerae O1

Of over 200 different identified Vibrio cholerae serogroups only the O1 serogroup is consistently associated with endemic and epidemic cholera disease. The O1 serogroup has two serologically distinguishable variants, the Ogawa and Inaba serotypes, which differ only by a methyl group present on the terminal sugar of the Ogawa O-antigen but absent from Inaba strains. This methylation is catalyzed by a methyltransferase encoded by the wbeT gene, which in Inaba strains is disrupted by mutation. It is currently thought that there is little difference between the two serotypes. However, here we show, using isogenic pairs of O1 El Tor V. cholerae, that Inaba strains show significantly different patterns of gene expression and are significantly less able than the corresponding Ogawa strains to cause cholera in an infant mouse infection model. Our results suggest that changes in gene expression resulting from the loss of the wbeT gene lead to reduced virulence and possibly also reduced survival fitness outside the human host. Author SummaryThe bacterium Vibrio cholerae causes the pandemic diarrheal disease cholera. Despite many identified serotypes of V. cholerae only one, O1, causes pandemic cholera. The O1 serotype of pandemic V. cholerae has two distinguishable variants (called Ogawa and Inaba) long considered to be clinically and epidemiologically equivalent. Cholera outbreaks consist only of one the two variants at any time. In general, Ogawa strains cause the majority of outbreaks with relatively short-lived Inaba outbreaks occurring sporadically. We have suggested earlier that Inaba outbreaks occur during periods of environmental selective pressure against the Ogawa serotype. We demonstrate here that the two variants are not clinically equivalent. The Ogawa serotype is better able to respond to infection in an animal model by up regulating the expression of virulence genes essential for disease development. We suggest that this phenomenon is the result of wider ranging differences in gene expression resulting from the mutation that converts Ogawa into Inaba strains, and may help to explain the dominance of the Ogawa serotype in nature.

microbiology↗