Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies
Several studies have shown that the first encounter with influenza virus shapes the immune response to future infections or vaccinations. However, a detailed analysis of the primary antibody response is lacking as this is difficult to study in humans. It is therefore not known what the frequency and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1026951/full |
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| author | Aafke Aartse Aafke Aartse Daniella Mortier Petra Mooij Sam Hofman Marlies M. van Haaren Marlies M. van Haaren Martin Corcoran Gunilla B. Karlsson Hedestam Dirk Eggink Dirk Eggink Mathieu Claireaux Mathieu Claireaux Willy M. J. M. Bogers Marit J. van Gils Marit J. van Gils Gerrit Koopman |
| author_facet | Aafke Aartse Aafke Aartse Daniella Mortier Petra Mooij Sam Hofman Marlies M. van Haaren Marlies M. van Haaren Martin Corcoran Gunilla B. Karlsson Hedestam Dirk Eggink Dirk Eggink Mathieu Claireaux Mathieu Claireaux Willy M. J. M. Bogers Marit J. van Gils Marit J. van Gils Gerrit Koopman |
| author_sort | Aafke Aartse |
| collection | DOAJ |
| description | Several studies have shown that the first encounter with influenza virus shapes the immune response to future infections or vaccinations. However, a detailed analysis of the primary antibody response is lacking as this is difficult to study in humans. It is therefore not known what the frequency and dynamics of the strain-specific hemagglutinin (HA) head- and stem-directed antibody responses are directly after primary influenza virus infection. Here, sera of twelve H1N1pdm2009 influenza virus-infected cynomolgus macaques were evaluated for HA-head and HA-stem domain antibody responses. We observed an early induction of HA-stem antibody responses, which was already decreased by day 56. In contrast, responses against the HA-head domain were low early after infection and increased at later timepoint. The HA-specific B cell repertoires in each animal showed diverse VH-gene usage with preferred VH-gene and JH-gene family usage for HA-head or HA-stem B cells but a highly diverse allelic variation within the VH-usage. HA-head B cells had shorter CDRH3s and higher VH-gene somatic hyper mutation levels relative to HA-stem B cells. In conclusion, our data suggest that HA-stem antibodies are the first to react to the infection while HA-head antibodies show a delayed response, but a greater propensity to enter the germinal center and undergo affinity maturation. |
| first_indexed | 2024-04-11T08:31:43Z |
| format | Article |
| id | doaj.art-ed98b50c9d954d01b3e2bfe78460e7bc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T08:31:43Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-ed98b50c9d954d01b3e2bfe78460e7bc2022-12-22T04:34:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10269511026951Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodiesAafke Aartse0Aafke Aartse1Daniella Mortier2Petra Mooij3Sam Hofman4Marlies M. van Haaren5Marlies M. van Haaren6Martin Corcoran7Gunilla B. Karlsson Hedestam8Dirk Eggink9Dirk Eggink10Mathieu Claireaux11Mathieu Claireaux12Willy M. J. M. Bogers13Marit J. van Gils14Marit J. van Gils15Gerrit Koopman16Department of Virology, Biomedical Primate Research Centre, Rijswijk, NetherlandsLaboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, University of Amsterdam, Amsterdam, NetherlandsDepartment of Virology, Biomedical Primate Research Centre, Rijswijk, NetherlandsDepartment of Virology, Biomedical Primate Research Centre, Rijswijk, NetherlandsDepartment of Parasitology, Biomedical Primate Research Centre, Rijswijk, NetherlandsLaboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, NetherlandsDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet (KI), Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet (KI), Stockholm, SwedenLaboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, NetherlandsLaboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, NetherlandsDepartment of Virology, Biomedical Primate Research Centre, Rijswijk, NetherlandsLaboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, University of Amsterdam, Amsterdam, NetherlandsAmsterdam Institute for Infection and Immunity, Infectious Diseases, Amsterdam, NetherlandsDepartment of Virology, Biomedical Primate Research Centre, Rijswijk, NetherlandsSeveral studies have shown that the first encounter with influenza virus shapes the immune response to future infections or vaccinations. However, a detailed analysis of the primary antibody response is lacking as this is difficult to study in humans. It is therefore not known what the frequency and dynamics of the strain-specific hemagglutinin (HA) head- and stem-directed antibody responses are directly after primary influenza virus infection. Here, sera of twelve H1N1pdm2009 influenza virus-infected cynomolgus macaques were evaluated for HA-head and HA-stem domain antibody responses. We observed an early induction of HA-stem antibody responses, which was already decreased by day 56. In contrast, responses against the HA-head domain were low early after infection and increased at later timepoint. The HA-specific B cell repertoires in each animal showed diverse VH-gene usage with preferred VH-gene and JH-gene family usage for HA-head or HA-stem B cells but a highly diverse allelic variation within the VH-usage. HA-head B cells had shorter CDRH3s and higher VH-gene somatic hyper mutation levels relative to HA-stem B cells. In conclusion, our data suggest that HA-stem antibodies are the first to react to the infection while HA-head antibodies show a delayed response, but a greater propensity to enter the germinal center and undergo affinity maturation.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1026951/fullinfluenza A virushemagglutininHA-stemHA-headprimary responseantibody response |
| spellingShingle | Aafke Aartse Aafke Aartse Daniella Mortier Petra Mooij Sam Hofman Marlies M. van Haaren Marlies M. van Haaren Martin Corcoran Gunilla B. Karlsson Hedestam Dirk Eggink Dirk Eggink Mathieu Claireaux Mathieu Claireaux Willy M. J. M. Bogers Marit J. van Gils Marit J. van Gils Gerrit Koopman Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies Frontiers in Immunology influenza A virus hemagglutinin HA-stem HA-head primary response antibody response |
| title | Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies |
| title_full | Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies |
| title_fullStr | Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies |
| title_full_unstemmed | Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies |
| title_short | Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies |
| title_sort | primary antibody response after influenza virus infection is first dominated by low mutated ha stem antibodies followed by higher mutated ha head antibodies |
| topic | influenza A virus hemagglutinin HA-stem HA-head primary response antibody response |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1026951/full |
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