ABSTRACT
Pre-existing immunity to influenza is dependent on a number of factors and can vary greatly within and across influenza subtypes. In this study, volunteers (aged 18-85 years) were vaccinated with split, inactivated FluzoneTM in four consecutive influenza seasons from 2013 to 2016. The impact of repeat vaccination on breadth and durability of functional antibodies was assessed for total IgG and IgA anti-hemagglutinin (HA) binding antibodies and hemagglutination-inhibition (HAI) activity against both influenza B lineages. Many subjects were able to maintain high seroprotective titers to the vaccine strains in subsequent years, which resulted in low vaccine-induced seroconversion rates. This was especially evident in younger subjects who typically had higher titers and maintained these titers into the following season. In contrast, the HAI titers in elderly subjects were generally lower and more likely to decline prior to the start of the next influenza season. Immunological recall or 'back-boosting' to antigenically related viruses was associated with seroconversion. Overall, influenza vaccination in both younger and older people elicited broadly reactive immune responses within a lineage, as well as cross-reactive immune responses between lineages. This study exemplified the impact that age and influenza exposure history have on determining an individual's ability to respond to future influenza infections.
Subject(s)
Age Factors , Antibodies, Viral/blood , Immunologic Memory , Influenza B virus/immunology , Influenza Vaccines/immunology , Influenza, Human/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , Drug Administration Schedule , Female , Hemagglutination Inhibition Tests , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Male , Middle Aged , Seroconversion , Young AdultABSTRACT
Multiple age-related and injury-induced characteristics of the adult central nervous system (CNS) pose barriers to axonal regeneration and functional recovery following injury. In situ gene therapy is a promising approach to address the limited availability of growth-promoting biomolecules at CNS injury sites. The ultimate goal of our work is to develop, a cationic amphiphilic copolymer for simultaneous delivery of drug and therapeutic nucleic acids to promote axonal regeneration and plasticity after spinal cord injury. Previously, we reported the synthesis and characterization of a cationic amphiphilic copolymer, poly (lactide-co-glycolide)-graft-polyethylenimine (PgP) and its ability to efficiently transfect cells with pDNA in the presence of serum. We also demonstrated the efficacy of PgP as a therapeutic siRhoA carrier in a rat compression spinal cord injury model. In this work, we show that PgP/pDNA polyplexes provide improved stability in the presence of competing polyanions and nuclease protection in serum relative to conventional branched polyethylenimine control. PgP/pDNA polyplexes maintain bioactivity for transfection after lyophilization/reconstitution and during storage at 4 °C for up to 5 months, important features for commercial and clinical application. We also demonstrate that PgP/pDNA polyplexes loaded with a hydrophobic fluorescent dye are retained in local neural tissue for up to 5 days and that PgP can efficiently deliver pß-Gal in a rat compression SCI model.
