Biology subjects

Treanor, J. J.

Publications and source records attributed to Treanor, J. J..

2 recordsLinked to original sources

bioRxiv2021

Broadly-reactive IgG responses to heterologous H5 prime-boost influenza vaccination are shaped by antigenic relatedness to priming strains

Prime-boost vaccinations of humans with different H5 strains have generated broadly protective antibody levels. However, the effect of an individuals H5 exposure history on antibody responses to subsequent H5 vaccination is poorly understood. To investigate this, we analyzed the IgG response to H5 A/Indonesia/5/2005 (Ind05) vaccination in three cohorts: (1) a double primed group that received two H5 vaccinations: A/Vietnam/203/2004 (Vie04) 5 years ago and A/Hong Kong/156/1997 (HK97) 11 years ago, (2) a single primed group that received Vie04 5 years ago, and (3) an H5-naive group that received two doses of the Ind05 vaccine 28 days apart. Hemagglutinin (HA)-reactive IgG levels were estimated by multiplex assay against an HA panel that included 21 H5 strains and 9 other strains representing H1, H3, H7, and H9 subtypes. Relative HA antibody landscapes were generated to quantitatively analyze the magnitude and breadth of antibody binding after vaccination. We found that short-interval prime-boosting with the Ind05 in the naive group generated a low anti-H5 response. Both primed groups generated robust antibody responses reactive to a broad range of H5 strains after boosting with Ind05; IgG antibody levels persisted longer in subjects who had been double primed years ago. Notably, the IgG responses were strongest against the first priming H5 strain, that reflecting influenza virus immune imprinting. Finally, the broad anti-H5 IgG response was stronger against strains having a small antigenic distance to the initial priming strain. IMPORTANCEThe antigenic shift and draft of hemagglutinin (HA) in influenza viruses is accepted as one of the major reasons for immune evasion. The analysis of B cell immune responses to influenza infection and vaccination is complicated by the impact of exposure history and antibody cross-reaction between antigenically similar influenza strains. To assist in such analyses, the influenza "antibody landscape" method has been used to analyze and visualize the relationship of antibody mediated immunity to the antigenic distance between influenza strains. In this study, we describe a "relative antibody landscape" method, calculating the antigenic distance between the vaccine influenza strain and other H5 strains, and using this relative antigenic distance to plot with the anti-H5 IgG levels post-vaccination. This new method quantitatively estimates and visualizes the correlation between the humoral response to a particular influenza strain, and the antigenic distance to other strains. Our findings demonstrate the effect of H5 exposure history on H5 vaccine responses quantified by the relative antibody landscape method.

immunology↗

bioRxiv2020

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

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 de1ne 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-speci1c, 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 speci1c 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. IMPORTANCEA signi1cant obstacle to development of a universal influenza vaccine is understanding the relationship between multidimensional host humoral immunity, prior antigen exposure, and viral antigenicity. In this study, we used a multiplexed antibody assay to measure antibody cross-reactivities against antigenically similar H5 influenza virus strains. This work uses a novel method, relative antibody landscapes, to analyze the relationship between immune response and antigenic distance between the target H5 vaccine HA and other HAs in the assay after a boosting vaccination. This method improves analysis of immune responses by relating antigen exposure history to the influenza vaccination antibody response. This study also revealed that multiple vaccine boosting over several years can generate high levels of long-lasting cross-reactive antibodies against the priming H5 strains vaccine that subjects received, suggesting the HA imprinting mechanism(s) have a strong influence in the adult antibody response to H5 MIV vaccination.

immunology↗