Dataset Information

Hemagglutination Inhibition (HAI) antibody landscapes after vaccination with H7Nx virus like particles.

ABSTRACT:

Background

A systemic evaluation of the antigenic differences of the H7 influenza hemagglutinin (HA) proteins, especially for the viruses isolated after 2016, are limited. The purpose of this study was to investigate the antigenic differences of major H7 strains with an ultimate aim to discover H7 HA proteins that can elicit protective receptor-binding antibodies against co-circulating H7 influenza strains.

Method

A panel of eight H7 influenza strains were selected from 3,633 H7 HA amino acid sequences identified over the past two decades (2000-2018). The sequences were expressed on the surface of virus like particles (VLPs) and used to vaccinate C57BL/6 mice. Serum samples were collected and tested for hemagglutination-inhibition (HAI) activity. The vaccinated mice were challenged with lethal dose of H7N9 virus, A/Anhui/1/2013.

Results

VLPs expressing the H7 HA antigens elicited broadly reactive antibodies each of the selected H7 HAs, except the A/Turkey/Italy/589/2000 (Italy/00) H7 HA. A putative glycosylation due to an A169T substitution in antigenic site B was identified as a unique antigenic profile of Italy/00. Introduction of the putative glycosylation site (H7 HA-A169T) significantly altered the antigenic profile of HA of the A/Anhui/1/2013 (H7N9) strain.

Conclusion

This study identified key amino acid mutations that result in severe vaccine mismatches for future H7 epidemics. Future universal influenza vaccine candidates will need to focus on viral variants with these key mutations.

SUBMITTER: Jang H

PROVIDER: S-EPMC7971484 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The hemagglutination inhibition assay (HAI) is widely used to evaluate vaccine-induced antibody responses as well as to antigenically characterize influenza viruses. The results of an HAI assay are based on an endpoint titration where the titers are generally manually interpreted and recorded by a well-trained expert. For serological applications, the lack of standardization in endpoint interpretation and interference from non-specific inhibitors in clinical samples can translate into a high degree of variability in the results. For example, tilting HAI plates at 45-60 degrees to look for a "tear drop pattern" with avian red blood cells is a common practice by many, but not all, research laboratories. In this work, we tested the hypothesis that an automated image analysis algorithm can be used to achieve an accurate and non-subjective interpretation of HAI assays-specifically without the need to tilt plates. In a side-by-side comparison study performed during FDA's biannual serological screening process for influenza viruses, titer calls for more than 2200 serum samples were made by the Cypher One automated hemagglutination analyzer without tilting and by an expert human with tilting. The comparison yielded 95.6% agreement between the expert reader and automated interpretation method (within ± 1 dilution) for the complete dataset. Performance was also evaluated relative to the type of red blood cell (turkey and guinea pig) and influenza strain (12 different viruses). For the subset that utilized guinea pig red blood cells (~44% of the samples), for which no plate tilting was required, the agreement with an expert reader was 97.2%. For the subset that utilized turkey red blood cells (~56% of the samples), for which plate tilting was necessary by the expert reader, the agreement was 94.3%. Overall these results support the postulate that algorithm-based interpretation of a digital record with no plate tilting could replace manual reading for greater consistency in HAI assays.