Front Immunol . Primary antibody response after influenza virus infection is first dominated by low-mutated HA-stem antibodies followed by higher-mutated HA-head antibodies

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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 ^{1 2} , Daniella Mortier ¹ , Petra Mooij ¹ , Sam Hofman ³ , Marlies M van Haaren ^{2 4} , Martin Corcoran ⁵ , Gunilla B Karlsson Hedestam ⁵ , Dirk Eggink ^{2 4} , Mathieu Claireaux ^{2 4} , Willy M J M Bogers ¹ , Marit J van Gils ^{2 4} , Gerrit Koopman ¹



Affiliations

• PMID: 36405682
• PMCID: PMC9670313
• DOI: 10.3389/fimmu.2022.1026951

Free PMC article

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_pdm2009 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.