Dataset Information

Extraction of the CDRH3 sequence of the mouse antibody repertoire selected upon influenza virus infection by subtraction of the background antibody repertoire.

ABSTRACT: Historically, antibody reactivity to pathogens and vaccine antigens has been evaluated using serological measurements of antigen-specific antibodies. However, it is difficult to evaluate all antibodies that contribute to various functions in a single assay, such as the measurement of the neutralizing antibody titer. Bulk antibody repertoire analysis using next-generation sequencing is a comprehensive method for analyzing the overall antibody response; however, it is unreliable for estimating antigen-specific antibodies due to individual variation. To address this issue, we propose a method to subtract the background signal from the repertoire of data of interest. In this study, we analyzed changes in antibody diversity and inferred the heavy-chain complementarity-determining region 3 (CDRH3) sequences of antibody clones that were selected upon influenza virus infection in a mouse model using bulk repertoire analysis. A decrease in the diversity of the antibody repertoire was observed upon viral infection, along with an increase in neutralizing antibody titers. Using kernel density estimation of sequences in a high-dimensional sequence space with background signal subtraction, we identified several clusters of CDRH3 sequences induced upon influenza virus infection. Most of these repertoires were detected more frequently in infected mice than in uninfected control mice, suggesting that infection-specific antibody sequences can be extracted using this method. Such an accurate extraction of antigen- or infection-specific repertoire information will be a useful tool for vaccine evaluation in the future.

Importance

As specific interactions between antigens and cell-surface antibodies trigger the proliferation of B-cell clones, the frequency of each antibody sequence in the samples reflects the size of each clonal population. Nevertheless, it is extremely difficult to extract antigen-specific antibody sequences from the comprehensive bulk antibody sequences obtained from blood samples due to repertoire bias influenced by exposure to dietary antigens and other infectious agents. This issue can be addressed by subtracting the background noise from the post-immunization or post-infection repertoire data. In the present study, we propose a method to quantify repertoire data from comprehensive repertoire data. This method allowed subtraction of the background repertoire, resulting in more accurate extraction of expanded antibody repertoires upon influenza virus infection. This accurate extraction of antigen- or infection-specific repertoire information is a useful tool for vaccine evaluation.

SUBMITTER: Shingai M

PROVIDER: S-EPMC10949447 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Extraction of the CDRH3 sequence of the mouse antibody repertoire selected upon influenza virus infection by subtraction of the background antibody repertoire.

Shingai Masashi M Iida Sayaka S Kawai Naoko N Kawahara Mamiko M Sekiya Toshiki T Ohno Marumi M Nomura Naoki N Handabile Chimuka C Kawakita Tomomi T Omori Ryosuke R Yamagishi Junya J Sano Kaori K Ainai Akira A Suzuki Tadaki T Ohnishi Kazuo K Ito Kimihito K Kida Hiroshi H

Journal of virology 20240207 3

Historically, antibody reactivity to pathogens and vaccine antigens has been evaluated using serological measurements of antigen-specific antibodies. However, it is difficult to evaluate all antibodies that contribute to various functions in a single assay, such as the measurement of the neutralizing antibody titer. Bulk antibody repertoire analysis using next-generation sequencing is a comprehensive method for analyzing the overall antibody response; however, it is unreliable for estimating ant ...[more]

PMID: 38323813

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Project description:Molecular Features of the Serological IgG Repertoire Elicited by Egg-based, Cell-based, or Recombinant HA Seasonal Influenza Vaccines. __sample information__ Donorname day0S1 or day28S2 Elu or FT Pf number A1 S1 FT 7649_JL_5a.raw A1 S1 FT 7649_JL_5b.raw A1 S1 FT 7649_JL_5c.raw A1 S2 FT 7649_JL_7a.raw A1 S2 FT 7649_JL_7b.raw A1 S2 FT 7649_JL_7c.raw A1 S1 Elu 7649_JL_6a.raw A1 S1 Elu 7649_JL_6b.raw A1 S1 Elu 7649_JL_6c.raw A1 S2 Elu 7649_JL_8a.raw A1 S2 Elu 7649_JL_8b.raw A1 S2 Elu 7649_JL_8c.raw A2 S1 FT 8078_JP_1a.raw A2 S1 FT 8078_JP_1b.raw A2 S1 FT 8078_JP_1c.raw A2 S2 FT 8078_JP_2a.raw A2 S2 FT 8078_JP_2b.raw A2 S2 FT 8078_JP_2c.raw A2 S1 Elu 8078_JP_3a.raw A2 S1 Elu 8078_JP_3b.raw A2 S1 Elu 8078_JP_3c.raw A2 S2 Elu 8078_JP_4a.raw A2 S2 Elu 8078_JP_4b.raw A2 S2 Elu 8078_JP_4c.raw A3 S1 FT 8116_JP_1a.raw A3 S1 FT 8116_JP_1b.raw A3 S1 FT 8116_JP_1c.raw A3 S2 FT 8116_JP_2a.raw A3 S2 FT 8116_JP_2b.raw A3 S2 FT 8116_JP_2c.raw A3 S1 Elu 8116_JP_3a.raw A3 S1 Elu 8116_JP_3b.raw A3 S1 Elu 8116_JP_3c.raw A3 S2 Elu 8116_JP_4a.raw A3 S2 Elu 8116_JP_4b.raw A3 S2 Elu 8116_JP_4c.raw A4 S1 FT 8149_JP_1a.raw A4 S1 FT 8149_JP_1b.raw A4 S1 FT 8149_JP_1c.raw A4 S2 FT 8149_JP_2a.raw A4 S2 FT 8149_JP_2b.raw A4 S2 FT 8149_JP_2c.raw A4 S1 Elu 8149_JP_3a.raw A4 S1 Elu 8149_JP_3b.raw A4 S1 Elu 8149_JP_3c.raw A4 S2 Elu 8149_JP_4a.raw A4 S2 Elu 8149_JP_4b.raw A4 S2 Elu 8149_JP_4c.raw A5 S1 FT 8209_JP_1a.raw A5 S1 FT 8209_JP_1b.raw A5 S1 FT 8209_JP_1c.raw A5 S2 FT 8209_JP_2a.raw A5 S2 FT 8209_JP_2b.raw A5 S2 FT 8209_JP_2c.raw A5 S1 Elu 8209_JP_3a.raw A5 S1 Elu 8209_JP_3b.raw A5 S1 Elu 8209_JP_3c.raw A5 S2 Elu 8209_JP_4a.raw A5 S2 Elu 8209_JP_4b.raw A5 S2 Elu 8209_JP_4c.raw B1 S1 FT 7924_JL_1a.raw B1 S1 FT 7924_JL_1b.raw B1 S1 FT 7924_JL_1c.raw B1 S2 FT 7924_JL_2a.raw B1 S2 FT 7924_JL_2b.raw B1 S2 FT 7924_JL_2c.raw B1 S1 Elu 7924_JL_4a.raw B1 S1 Elu 7924_JL_4b.raw B1 S1 Elu 7924_JL_4c.raw B1 S2 Elu 7924_JL_5a.raw B1 S2 Elu 7924_JL_5b.raw B1 S2 Elu 7924_JL_5c.raw B2 S1 FT 7947_JL_1a.raw B2 S1 FT 7947_JL_1b.raw B2 S1 FT 7947_JL_1c.raw B2 S2 FT 7947_JL_2a.raw B2 S2 FT 7947_JL_2b.raw B2 S2 FT 7947_JL_2c.raw B2 S1 Elu 7947_JL_3a.raw B2 S1 Elu 7947_JL_3b.raw B2 S1 Elu 7947_JL_3c.raw B2 S2 Elu 7947_JL_4a.raw B2 S2 Elu 7947_JL_4b.raw B2 S2 Elu 7947_JL_4c.raw B3 S1 FT 8129_JL_1a.raw B3 S1 FT 8129_JL_1b.raw B3 S1 FT 8129_JL_1c.raw B3 S2 FT 8129_JL_2a.raw B3 S2 FT 8129_JL_2b.raw B3 S2 FT 8129_JL_2c.raw B3 S1 Elu 8129_JL_3a.raw B3 S1 Elu 8129_JL_3b.raw B3 S1 Elu 8129_JL_3c.raw B3 S2 Elu 8129_JL_4a.raw B3 S2 Elu 8129_JL_4b.raw B3 S2 Elu 8129_JL_4c.raw B4 S1 FT 8164_JP_1a.raw B4 S1 FT 8164_JP_1b.raw B4 S1 FT 8164_JP_1c.raw B4 S2 FT 8164_JP_2a.raw B4 S2 FT 8164_JP_2b.raw B4 S2 FT 8164_JP_2c.raw B4 S1 Elu 8164_JP_3a.raw B4 S1 Elu 8164_JP_3b.raw B4 S1 Elu 8164_JP_3c.raw B4 S2 Elu 8164_JP_4a.raw B4 S2 Elu 8164_JP_4b.raw B4 S2 Elu 8164_JP_4c.raw B5 S1 FT 8237_JP_1a.raw B5 S1 FT 8237_JP_1b.raw B5 S1 FT 8237_JP_1c.raw B5 S2 FT 8237_JP_2a.raw B5 S2 FT 8237_JP_2b.raw B5 S2 FT 8237_JP_2c.raw B5 S1 Elu 8237_JP_3a.raw B5 S1 Elu 8237_JP_3b.raw B5 S1 Elu 8237_JP_3c.raw B5 S2 Elu 8237_JP_4a.raw B5 S2 Elu 8237_JP_4b.raw B5 S2 Elu 8237_JP_4c.raw C1 S1 FT 8108_JP_1a.raw C1 S1 FT 8108_JP_1b.raw C1 S1 FT 8108_JP_1c.raw C1 S2 FT 8108_JP_2a.raw C1 S2 FT 8108_JP_2b.raw C1 S2 FT 8108_JP_2c.raw C1 S1 Elu 8108_JP_3a.raw C1 S1 Elu 8108_JP_3b.raw C1 S1 Elu 8108_JP_3c.raw C1 S2 Elu 8108_JP_4a.raw C1 S2 Elu 8108_JP_4b.raw C1 S2 Elu 8108_JP_4c.raw C2 S1 FT 8048_JL_1a.raw C2 S1 FT 8048_JL_1b.raw C2 S1 FT 8048_JL_1c.raw C2 S2 FT 8048_JL_2a.raw C2 S2 FT 8048_JL_2b.raw C2 S2 FT 8048_JL_2c.raw C2 S1 Elu 8048_JL_3a.raw C2 S1 Elu 8048_JL_3b.raw C2 S1 Elu 8048_JL_3c.raw C2 S2 Elu 8048_JL_4a.raw C2 S2 Elu 8048_JL_4b.raw C2 S2 Elu 8048_JL_4c.raw C3 S1 FT 8068_JP_1a.raw C3 S1 FT 8068_JP_1b.raw C3 S1 FT 8068_JP_1c.raw C3 S2 FT 8068_JP_2a.raw C3 S2 FT 8068_JP_2b.raw C3 S2 FT 8068_JP_2c.raw C3 S1 Elu 8068_JP_3a.raw C3 S1 Elu 8068_JP_3b.raw C3 S1 Elu 8068_JP_3c.raw C3 S2 Elu 8108_JP_5a.raw C3 S2 Elu 8108_JP_5b.raw C3 S2 Elu 8108_JP_5c.raw C4 S1 FT 8203_JP_1a.raw C4 S1 FT 8203_JP_1b.raw C4 S1 FT 8203_JP_1c.raw C4 S2 FT 8203_JP_2a.raw C4 S2 FT 8203_JP_2b.raw C4 S2 FT 8203_JP_2c.raw C4 S1 Elu 8203_JP_3a.raw C4 S1 Elu 8203_JP_3b.raw C4 S1 Elu 8203_JP_3c.raw C4 S2 Elu 8203_JP_4a.raw C4 S2 Elu 8203_JP_4b.raw C4 S2 Elu 8203_JP_4c.raw C5 S1 FT 8258_JP_1a.raw C5 S1 FT 8258_JP_1b.raw C5 S1 FT 8258_JP_1c.raw C5 S2 FT 8258_JP_2a.raw C5 S2 FT 8258_JP_2b.raw C5 S2 FT 8258_JP_2c.raw C5 S1 Elu 8258_JP_3a.raw C5 S1 Elu 8258_JP_3b.raw C5 S1 Elu 8258_JP_3c.raw C5 S2 Elu 8258_JP_4a.raw C5 S2 Elu 8258_JP_4b.raw C5 S2 Elu 8258_JP_4c.raw

Project description:BackgroundVaccines dramatically affect an individual's adaptive immune system and thus provide an excellent means to study human immunity. Upon vaccination, the B cells that express antibodies (Abs) that happen to bind the vaccine are stimulated to proliferate and undergo mutagenesis at their Ab locus. This process may alter the composition of B cell lineages within an individual, which are known collectively as the antibody repertoire (AbR). Antibodies are also highly expressed in whole blood, potentially enabling RNA sequencing (RNA-seq) technologies to query this diversity. Less is known about the diversity of AbR responses across individuals to a given vaccine and if individuals tend to yield a similar response to the same antigenic stimulus.MethodsHere we implement a bioinformatic pipeline that extracts the AbR information from a time-series RNA-seq dataset of five patients who were administered a seasonal trivalent influenza vaccine (TIV). We harness the detailed time-series nature of this dataset and use methods based in functional data analysis (FDA) to identify the Abs that respond to the vaccine. We then design and implement rigorous statistical tests in order to ask whether or not these patients exhibit a convergent AbR response to the same TIV.ResultsWe find that high-resolution time-series data can be used to help identify the Abs that respond to an antigenic stimulus and that this response can exhibit a convergent nature across patients inoculated with the same vaccine. However, correlations in AbR diversity among individuals prior to inoculation can confound inference of a convergent signal unless it is taken into account.ConclusionsWe developed a framework to identify the elements of an AbR that respond to an antigen. This information could be used to understand the diversity of different immune responses in different individuals, as well as to gauge the effectiveness of the immune response to a given stimulus within an individual. We also present a framework for testing a convergent hypothesis between AbRs; a hypothesis that is more difficult to test than previously appreciated. Our discovery of a convergent signal suggests that similar epitopes do select for antibodies with similar sequence characteristics.

Dataset Information

Extraction of the CDRH3 sequence of the mouse antibody repertoire selected upon influenza virus infection by subtraction of the background antibody repertoire.

Importance

Publications

Extraction of the CDRH3 sequence of the mouse antibody repertoire selected upon influenza virus infection by subtraction of the background antibody repertoire.

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