Cross-reactive anti-hemagglutinin (HA) IgG responses are shaped by previous long-interval monovalent H5 vaccination and highly correlated with HA antigenic distance

Abstract

Avian H5 influenza is an emerging influenza strain with the potential for human pandemic spread. One unresolved issue in pandemic vaccine preparedness is to what extent a vaccine recall response depends on the interval between the priming and boosting vaccinations. In this study, we analyzed the anti-H5 HA IgG responses to an H5 A/Indonesia/5/2005 boosting vaccination in three cohorts: (1) a short interval boosting cohort that received a prime and boost 28 days apart, (2) a long-interval boosting cohort that received an H5 A/Vietnam/203/2004 priming vaccination 5 years before boosting, and (3) a double long-boost cohort that received single doses of all three vaccines separated by 5-6 year intervals. Anti-HA IgG levels were measured using a multiple-plex assay against 21 H5 and 16 seasonal strains covering both influenza phylogenetic groups. We used the antigentic distance between the vaccine strain and each HA in the assay panel to define the antibody response landscape. Both single and double long-interval boosting with the H5 variant vaccine elicited a broad antibody response to all H5 subtype strains, and double boosting resulted in sustained, vaccine-specific, anti-HA IgG levels over a six month period. Antibody-mediated immune responses were shaped by prior H5 exposure history, and the magnitude of both vaccine specific and cross-reactive anti-H5 HA IgG responses was highly correlated with the relative antigenic distance between the measured and the vaccine HAs. We conclude that the relative antibody landscape method can be used to quantify the phenomenon of antigenic imprinting on human influenza vaccine immune responses.

Antibody Mediated Immunity to SARS-CoV-2 and Human Coronaviruses: Multiplex Beads Assay and Volumetric Absorptive Microsampling to Generate Immune Repertoire Cartography

“…Using the anti-HCoVs positive control standard serum (STD-CoV) in mPlex-CoV assay, we next generated 5 parameter logistic curves to map the assay MFI results to antigen-specific antibody concentrations with the method previously described for influenza anti-hemagglutinin antibodies (19)(20)(21). This allows direct comparison of absolute individual isotype antibody concentrations against each target strain HCoV S or N protein.…”

“…Multiplex systems serology assays that measure IgG binding for multiple antigens have been used to quantify antigenic distances between viral strains, track antibody cross-reactivity due to prior IgG exposure to similar viral strains, and provide quantitative measurements of IgG repertoire changes after infection or vaccination (17). We have previously described an influenza anti-hemagglutinin multiplex assay, mPlex-Flu, that has a continuous linear readout over 4.5 logs, and low Type-I (false positives, specificity) and Type-II (false negatives, sensitivity) errors (18)(19)(20). The mPlex-Flu assay provides absolute concentrations of antibodies against up to 50 target analytes (17,(21)(22)(23) with extremely low inter-and intra-assay variance, greater precision of clinical trial group statistical comparisons (20,24), and a very high correlation with functional viral binding and inhibition assays.…”