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

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 6

HA stem–specific Ab response in newborn and adult AGMs following IAV infection.

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HA stem–specific Ab response in newborn and adult AGMs following IAV inf...
IgM (A) and IgG (B) binding to the HA stem region in plasma samples from naive and infected animals (n = 4/group) was quantified by ELISA using a headless California/09 HA stem construct. (C) The presence of stem-specific IgG was also assessed in BAL collected at day 14 p.i. Pre- and postinfection samples for adults are from the same animals. Naive newborn samples are from an age-matched control cohort. (D) The capacity of stem mAb CR9114 to competitively inhibit IgG binding to HA and Ca09 was assessed by ELISA in plasma collected at day 14 p.i. from newborns and adults. Plates were preincubated with serial dilutions of CR9114. Plasma was diluted at 1:80 and added to plates coated with HA or the stem construct as indicated. IgA Ab in the plasma (E) and BAL (F) collected at day 14 p.i. was also evaluated for Ab binding to the stem region. Plasma IgM and IgA assays were performed starting at a dilution of 1:10 and 1:20, respectively. The starting dilution for plasma IgG was 1:80 because of the high HA-specific Ab titer at day 14 p.i. BAL assays were performed at a starting dilution of 1:5. Significance was determined by unpaired 1-tailed t test; **P < 0.01, and ****P < 0.0001.