tetano
Editor, Senior Moderator
Front Immunol
. 2022 Nov 3;13:1026951.
doi: 10.3389/fimmu.2022.1026951. eCollection 2022.
Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies
Aafke Aartse[SUP] 1 2 [/SUP], Daniella Mortier[SUP] 1 [/SUP], Petra Mooij[SUP] 1 [/SUP], Sam Hofman[SUP] 3 [/SUP], Marlies M van Haaren[SUP] 2 4 [/SUP], Martin Corcoran[SUP] 5 [/SUP], Gunilla B Karlsson Hedestam[SUP] 5 [/SUP], Dirk Eggink[SUP] 2 4 [/SUP], Mathieu Claireaux[SUP] 2 4 [/SUP], Willy M J M Bogers[SUP] 1 [/SUP], Marit J van Gils[SUP] 2 4 [/SUP], Gerrit Koopman[SUP] 1 [/SUP]
Affiliations
Abstract
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 H1N1[SUB]pdm2009[/SUB] 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.
Keywords: HA-head; HA-stem; antibody response; hemagglutinin; influenza A virus; primary response.
. 2022 Nov 3;13:1026951.
doi: 10.3389/fimmu.2022.1026951. eCollection 2022.
Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies
Aafke Aartse[SUP] 1 2 [/SUP], Daniella Mortier[SUP] 1 [/SUP], Petra Mooij[SUP] 1 [/SUP], Sam Hofman[SUP] 3 [/SUP], Marlies M van Haaren[SUP] 2 4 [/SUP], Martin Corcoran[SUP] 5 [/SUP], Gunilla B Karlsson Hedestam[SUP] 5 [/SUP], Dirk Eggink[SUP] 2 4 [/SUP], Mathieu Claireaux[SUP] 2 4 [/SUP], Willy M J M Bogers[SUP] 1 [/SUP], Marit J van Gils[SUP] 2 4 [/SUP], Gerrit Koopman[SUP] 1 [/SUP]
Affiliations
- PMID: 36405682
- PMCID: PMC9670313
- DOI: 10.3389/fimmu.2022.1026951
Abstract
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 H1N1[SUB]pdm2009[/SUB] 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.
Keywords: HA-head; HA-stem; antibody response; hemagglutinin; influenza A virus; primary response.