Biology subjects

Danzy, S.

Publications and source records attributed to Danzy, S..

3 recordsLinked to original sources

bioRxiv2026

Distinct Longitudinal Antibody Responses Following Primary Influenza Infection or Vaccination in Infants: A Prospective Birth Cohort Study

The longitudinal effects of initial influenza exposure on the magnitude, persistence, and antigen specificity of antibody responses during infancy remain incompletely understood. We investigated humoral antibody responses following primary influenza infection or seasonal vaccination in a prospective US birth cohort with weekly respiratory surveillance for influenza infection. Influenza-specific serum IgG binding to H1 and H3 haemagglutinin (HA) antigens, HA inhibition (HAI), and live-virus neutralizing antibody responses were assessed longitudinally. To minimize influence of maternally derived antibodies, analyses of primary exposure responses were restricted to infants for whom influenza-specific maternal antibodies had declined below the assay detection limit before exposure. Antibody responses were compared following primary infection and vaccination and examined after subsequent annual vaccination. We found that maternal influenza-specific IgG declined rapidly during early infancy. Among infants without detectable pre-exposure influenza-specific antibodies, primary influenza infection was associated with greater post-exposure antibody responses and less measurable decline over follow-up than primary vaccination. These groups differed in age, calendar season, and exposure characteristics, limiting direct attribution of these differences to route of exposure. In infants with previous influenza infection followed by vaccination, responses after subsequent vaccination initially showed greater binding to the previously infecting subtype among the tested HA antigens. With repeated vaccination, responses became more distributed across the tested antigens. Our findings reveal differences in the magnitude, persistence, and antigen specificity of antibody responses according to the nature and sequence of influenza exposure. By prospectively capturing early-life exposures, this study provides longitudinal evidence linking exposure history to subsequent humoral antibody responses.

immunology↗

bioRxiv2026

Within-host adaptive evolution is limited by genetic drift in experimental human influenza A virus infections

Selection of advantageous mutations drives the emergence of dominant variants during seasonal influenza epidemics. However, within-host detection of such variants remains rare, limiting our understanding of how selection operates at the scale of individual hosts. In this study, we used a controlled human infection model to examine the within-host evolutionary dynamics in thirteen participants intranasally infected with a seasonal H3N2 influenza A virus. Although this clinical trial is ongoing, our work represents a pre-planned, interim, exploratory analysis. Results in this system were contrasted with those observed in a ferret model of infection. The inoculum, used in both humans and ferrets, carried standing diversity that enabled evaluation of variant trajectories during infection. Although the dynamics were variable among participants, in humans, the minor variants in the PA and NP gene segments tended to increase in frequency as infection progressed. Variant dynamics were more consistent among ferrets but showed differences from humans in the fate of the minor NP allele. Based on these observations, we fit a population genetic model to longitudinal measurements of variant frequencies. Estimates of variant selection coefficients and effective viral population sizes indicated that in humans the two minor variants had a selective advantage over the major variants, but genetic drift was strong, limiting the efficiency of selection. In ferrets, the PA minor variant also was estimated to have a selective advantage, while the NP minor variant was estimated to have a selective disadvantage. Moreover, effective viral population sizes were estimated to be considerably higher in ferrets than in humans, indicating that genetic drift was weaker in ferrets. Our analyses reveal differing selective environments acting on influenza viruses in human and ferret hosts and indicate that selection at the within-host level is weakened by genetic drift.

microbiology↗

bioRxiv2019

Dysregulation of M segment gene expression contributes to influenza A virus host restriction

The M segment of the 2009 pandemic influenza A virus (IAV) has been implicated in its emergence into human populations. To elucidate the genetic contributions of the M segment to host adaptation, and the underlying mechanisms, we examined a panel of isogenic viruses that carry avian- or human-derived M segments. Avian, but not human, M segments restricted viral growth and transmission in mammalian model systems, and the restricted growth correlated with increased expression of M2 relative to M1. M2 overexpression was associated with intracellular accumulation of autophagosomes, which was alleviated by interference of the viral proton channel activity by amantadine treatment. As M1 and M2 are expressed from the M mRNA through alternative splicing, we separated synonymous and non-synonymous changes that differentiate human and avian M segments and found that dysregulation of gene expression leading to M2 overexpression diminished replication, irrespective of amino acid composition of M1 or M2. Moreover, in spite of efficient replication, virus possessing a human M segment that expressed avian M2 protein at low level did not transmit efficiently. We conclude that (i) determinants of transmission reside in the IAV M2 protein, and that (ii) control of M segment gene expression is a critical aspect of IAV host adaptation needed to prevent M2-mediated dysregulation of vesicular homeostasis.\n\nAuthor summaryInfluenza A virus (IAV) pandemics arise when a virus adapted to a non-human host overcomes species barriers to successfully infect humans and sustain human-to-human transmission. To gauge the adaptive potential and therefore pandemic risk posed by a particular IAV, it is critical to understand the mechanisms underlying viral adaptation to human hosts. Here, we focused on the role of one of IAVs eight gene segments, the M segment, in host adaptation. Comparing the growth of IAVs with avian- and human-derived M segments in avian and mammalian systems revealed that the avian M segment restricts viral growth specifically in mammalian cells. We show that the mechanism underlying this host range phenotype is a dysregulation of viral gene expression when the avian IAV M segment is transcribed in mammalian cells. In particular, excess production of the M2 protein results in viral interference with cellular functions on which the virus relies. Our results therefore reveal that the use of cellular machinery to control viral gene expression leaves the virus vulnerable to over- or under-production of critical viral gene products in a new host species.

microbiology↗