Dataset Information

B cell imprinting in children impairs antibodies to the hemagglutinin stalk

ABSTRACT: Immune imprinting or Original Antigenic Sin (OAS) is a phenomenon where the immune system preferentially recalls its initial response to a related, often evolving pathogen upon subsequent exposure. Despite its important implications for vaccine development, the causes of imprinting remain unclear. To understand the basis and impact of imprinting by influenza A viruses, we characterized the B cell responses of young children following consecutive first infections with divergent H1N1 and H3N2 strains. Children had a primary but otherwise similar B cell response to that of adults. Adult B cells commonly cross-reacted with past strains using more stereotyped and mutated immunoglobulin genes, indicating significant homosubtypic imprinting. In children, following consecutive heterosubtypic primary infections, up to 6% of memory B cells are H1/H3 cross-reactive and bind the highly conserved central stalk epitope, a lead target for broadly protective vaccine candidates. Over 90% of these B cells had higher affinity for the imprinting H3N2 strain, resulting in reduced breadth and neutralization potency against H1N1 strains. Mechanistically, the imprinting H3 and affected H1 strains shared a single residue change in the stalk epitope (D46N) that was central to the nearly universal shift in reactivity, despite differing by only a single atomic group. In conclusion, imprinting by influenza viruses can cause a deleterious shift of nearly the entire memory recall response against key, conserved epitopes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE297740 | GEO | 2026/01/29

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:LAIV and TIV are effective for prevention of influenza infection in children, but the mechanisms associated with protection are still not well defined. We analyzed the differences in B cell responses and transcriptional profiles. Compared to baseline, LAIV elicited a significant increase in naM-CM-/ve, memory and transitional B cells on day 30, while vaccination with TIV elicited an increase in number of plasmablasts on day 7. Antibody titers against the three vaccine strains (H1N1, H3N2 and B) were significantly higher in the TIV group and correlated with number of antibody-secreting cells. Regarding transcriptional profiles, both vaccines induced expression of interferon signaling, but at different time points, TIV on 1 day, and LAIV on day 7 day post-vaccination, the last only in children younger than 5 years old. Interferon-related genes over expressed in both vaccinated groups correlated with antibody titers of H3N2 vaccines strain. These results suggest that LAIV and TIV induced significant different B cell responses in vaccinated children. Early induction on interferon genes appears important for development of effective antibody responses. Longitudinal study with time points at baseline (day 0), 24hr, day 7 and day 30. 136 total samples analyzed. This was a prospective cohort of previously healthy children 6 months to 14 years of age enrolled between October 2011 and February 2012. Thirty seven subjects were randomized to receive one dose of either LAIV (FluMistM-BM-., MedImmune) (n= 20) or TIV (FluzoneM-BM-., Sanofi Pasteur) (n= 17). Two exceptions were applied to the randomization: four children with ages between 6 months and 2 years old received TIV, since LAIV is not licensed on this age group, and four children with controlled asthma also received TIV following CDCM-bM-^@M-^Ys recommendations. One child aged 6 months at the time of enrollment received two doses of the vaccine with one month interval apart, since it was his first influenza vaccination. Exclusion criteria included any medical comorbidities or chronic conditions (lung, kidney or heart disease), use of systemic steroids in the previous 2 weeks, and congenital or acquired immunodeficiencies. The 2011-2012 LAIV and TIV vaccines contained A/California/7/2009 (H1N1)-like, A/Perth/16/2009 (H3N2)-like and B/Brisbane/60/2008-like antigens, the same strains used on the 2010-2011 influenza vaccine. TIV recipients aged 6 to 35 months old received 0.25 mL intramuscularly and recipients aged 36 months and older received 0.5 mL. LAIV recipients received 0.2 mL by intranasal route, 0.1 mL per nostril. Blood samples were collected at four time points, on day zero prior to vaccination, and day 1, day 7 (range 6-8) and day 30 (range 27-33) post-vaccination.

Dataset Information

B cell imprinting in children impairs antibodies to the hemagglutinin stalk

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets