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Influenza-infected newborn and adult monkeys exhibit a strong primary antibody response to hemagglutinin stem
Elene Clemens, Davide Angeletti, Beth C. Holbrook, Masaru Kanekiyo, Matthew J. Jorgensen, Barney S. Graham, Jonathan Yewdell, Martha A. Alexander-Miller
Elene Clemens, Davide Angeletti, Beth C. Holbrook, Masaru Kanekiyo, Matthew J. Jorgensen, Barney S. Graham, Jonathan Yewdell, Martha A. Alexander-Miller
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Research Article Immunology

Influenza-infected newborn and adult monkeys exhibit a strong primary antibody response to hemagglutinin stem

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Abstract

The specificity of antibodies (Abs) generated against influenza A virus (IAV) infection can significantly alter protection and viral clearance. At present, the impact of age upon this process is relatively unexplored. Here, we evaluated the Ab response in newborn and adult African green monkeys following infection with IAV using a strain that enables us to determine the immunodominance (ID) hierarchy of the Ab response to hemagglutinin (HA), the principal target of protective Abs. This revealed altered ID patterns in the early IgM anti-HA response in newborns versus adults that converged over time. While the IgG ID profiles for HA in newborn and adult monkeys were similar, this was not the case for IgA. Importantly, HA stem–specific Abs were generated robustly and similarly in newborns and adults in terms of quality and quantity. Together, these results demonstrate that newborns and adults can differ in the Ab ID pattern established following infection and that the ID pattern can vary across isotypes. In addition, newborns have the ability to generate potent HA stem–specific Ab responses. Our findings further the understanding of the newborn response to IAV antigens and inform the development of improved vaccines for this at-risk population.

Authors

Elene Clemens, Davide Angeletti, Beth C. Holbrook, Masaru Kanekiyo, Matthew J. Jorgensen, Barney S. Graham, Jonathan Yewdell, Martha A. Alexander-Miller

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Figure 7

Avidity and neutralizing capacity of stem-binding Ab elicited in newborn and adult AGMs.

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Avidity and neutralizing capacity of stem-binding Ab elicited in newborn...
(A) Avidity of IgG to the California/09 stem construct was calculated as the NaSCN concentration giving a 50% reduction in optical absorbance compared with the untreated sample. (B) Neutralizing stem-specific Ab present at day 14 p.i. was assessed using a chimeric virus bearing an H5 head and N2 neuraminidase to limit detectable neutralization to stem-binding Abs. The limit of detection for the assay is designated by the dashed line; representative naive samples were all below threshold.

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