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Antibody immunodominance in the newborn immune response to influenza A virus

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Immune responses in early life are both quantitatively and qualitatively distinct from those of adulthood. While some of the unique features of newborn immunity confer adaptive benefit by facilitating tolerance during pregnancy and colonization by commensal microbiota, they can also leave newborns vulnerable to pathogens. Difficulties in elicitation of robust, persistent immune protection also make it difficult to compensate for this vulnerability through vaccination. Because of this, attempts to effectively vaccinate infants under 6 months of age against influenza viruses have been largely unsuccessful. This contributes to an increased burden of morbidity and mortality associated with influenza virus infection in this population that may potentially be preventable by vaccination. Effective vaccination against influenza viruses is challenging even in adults due to the high antigenic variability across viral strains. This has led to substantial interest in understanding how specific antibody responses are formed to variable and conserved components of influenza viruses, as immune responses tend to strongly favor recognition of variable epitopes. Here we investigated how the development of antibody to these preferred, or immunodominant, epitopes may be affected by the altered newborn system using a nonhuman primate (NHP) model of influenza A virus (IAV) infection. We found that while antibody immunodominance in the acute response to IAV infection is in many ways similar to that seen in adults, there may be previously undescribed differences in immunodominance dependent on antibody isotype or anatomic location. We also explored the possibility that antibody immunodominance following vaccination of newborn NHP can be modulated by use of Toll-like receptor (TLR) agonist adjuvants, and found that the use of TLR agonist adjuvants can partially mitigate the subdominance of antibody responses to conserved epitopes on the IAV protein hemagglutinin (HA). These findings further our understanding of how the newborn immune response can be modulated by vaccination to provide improved protection from influenza viruses.
Influenza vaccine
Clemens, Elene (author)
Alexander-Miller, Martha A (committee chair)
Lyles, Douglas (committee member)
Grayson, Jason (committee member)
Haas, Karen (committee member)
Peters, Timothy (committee member)
Soto-Pantoja, David (committee member)
2021-06-03T08:36:22Z (accessioned)
2021 (issued)
Microbiology & Immunology (discipline)
2026-05-17 (liftdate)
2026-05-17 (terms)
http://hdl.handle.net/10339/98848 (uri)
en (iso)
Wake Forest University
Antibody immunodominance in the newborn immune response to influenza A virus

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