title: Mucosal IgA responses in healthy adult volunteers following intranasal spray delivery of a live attenuated measles vaccine.
abstract: Measles remains an important cause of morbidity and mortality among children in the developing world. The goal of this study was to examine measles virus-specific mucosal immune responses in healthy immune (n = 24; plaque reduction neutralization [PRN] titers of ≥200 mIU/ml) and nonimmune (n = 24) young adult volunteers who received the monovalent Moraten measles vaccine via intranasal (spray delivery) or subcutaneous immunization. Serum, oral fluid, and nasal wash samples were examined for measles virus-specific and total IgG and IgA on day 0 (prior to vaccination) and on days 14, 28, and 90 after vaccination. Nonimmune subjects vaccinated subcutaneously developed high levels of measles virus PRN, IgG, and IgA antibodies in serum, oral fluid, and nasal washes. Total IgG and secretory IgA (sIgA) titers were increased in nasal washes, and total IgG was increased in oral fluid specimens. There was a strong correlation between PRN and measles virus-specific IgG titers measured in serum, oral fluid, and nasal washes, whereas a weak correlation was found between PRN and measles virus-specific IgA titers. Notably, intranasal measles vaccination resulted in increased production of measles virus-specific sIgA in oral fluid and nasal washes in nonimmune individuals, without evidence of a systemic immune response. In contrast, no significant vaccine-induced responses were observed in immune subjects, regardless of the route of immunization. These results demonstrate that (i) intranasal measles immunization can elicit a mucosal response independent of the induction of serum antibodies and (ii) both mucosal and systemic antibody responses following nasal or subcutaneous immunization are blunted by preexisting measles immunity.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Room 480, Baltimore, MD 21201, USA. jakub.simon@nanobio.com
authors.forename: Jakub K
authors.initials: JK
authors.lastname: Simon
authors.forename: Karina
authors.initials: K
authors.lastname: Ramirez
authors.forename: Lilian
authors.initials: L
authors.lastname: Cuberos
authors.forename: James D
authors.initials: JD
authors.lastname: Campbell
authors.forename: Jean F
authors.initials: JF
authors.lastname: Viret
authors.forename: Alma
authors.initials: A
authors.lastname: Muñoz
authors.forename: Rosanna
authors.initials: R
authors.lastname: Lagos
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Pasetti
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000032:analysis*; D004311:Double-Blind Method; D006805:Human Experimentation; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis*; D007074:Immunoglobulin G / Q000032:analysis; D007279:Injections, Subcutaneous; D008458:Measles Vaccine / Q000008:administration & dosage* / Q000276:immunology*; D008875:Middle Aged; D009061:Mouth Mucosa / Q000276:immunology; D009297:Nasal Mucosa / Q000276:immunology; D059085:Nasal Sprays; D044967:Serum / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008458:Measles Vaccine; D059085:Nasal Sprays