title: Effect of nanovaccine chemistry on humoral immune response kinetics and maturation.
abstract: Acute respiratory infections represent a significant portion of global morbidity and mortality annually. There is a critical need for efficacious vaccines against respiratory pathogens. To vaccinate against respiratory disease, pulmonary delivery is an attractive route because it mimics the route of natural infection and can confer both mucosal and systemic immunity. We have previously demonstrated that a single dose, intranasal vaccine based on polyanhydride nanoparticles elicited a protective immune response against Yersinia pestis for at least 40 weeks after immunization with F1-V. Herein, we investigate the effect of nanoparticle chemistry and its attributes on the kinetics and maturation of the antigen-specific serum antibody response. We demonstrate that manipulation of polyanhydride nanoparticle chemistry facilitated differential kinetics of development of antibody titers, avidity, and epitope specificity. The results provide new insights into the underlying role(s) of nanoparticle chemistry in providing long-lived humoral immunity and aid in the rational design of nanovaccine formulations to induce long-lasting and mature antibody responses.
authors.affiliation: Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011, USA. nbalaji@iastate.edu.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Haughney
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Ross
authors.forename: Paola M
authors.initials: PM
authors.lastname: Boggiatto
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wannemuehler
authors.forename: Balaji
authors.initials: B
authors.lastname: Narasimhan
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001682:Biological Availability; D056724:Immunity, Humoral / Q000187:drug effects*; D007114:Immunization / Q000379:methods; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010930:Plague / Q000378:metabolism / Q000517:prevention & control; D010931:Plague Vaccine / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D049388:Polyanhydrides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000068936:Theranostic Nanomedicine; D015010:Yersinia pestis / Q000276:immunology*
chemical_list: D010931:Plague Vaccine; D049388:Polyanhydrides