Adjuvanted Intranasal Norwalk Virus-Like Particle Vaccine Elicits Antibodies and Antibody-Secreting Cells That Express Homing Receptors for Mucosal and Peripheral Lymphoid Tissues

• Published in: The Journal of infectious diseases Vol. 202; no. 11; pp. 1649 - 1658
• Main Authors: El-Kamary, Samer S., Pasetti, Marcela F., Mendelman, Paul M., Frey, Sharon E., Bernstein, David I., Treanor, John J., Ferreira, Jennifer, Chen, Wilbur H., Sublett, Richard, Richardson, Charles, Bargatze, Robert F., Sztein, Marcelo B., Tacket, Carol O.
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 01.12.2010; University of Chicago Press; Oxford University Press
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Intranasal; Adolescent; Adult; Antibodies; Antibodies, Viral - biosynthesis; Antibodies, Viral - blood; Antibody-Producing Cells - immunology; Antibody-Producing Cells - metabolism; Antigens; Applied microbiology; Biological and medical sciences; Caliciviridae Infections - prevention & control; Caliciviridae Infections - virology; Chitosan - administration & dosage; Chitosan - immunology; Dosage; Double-Blind Method; Fundamental and applied biological sciences. Psychology; Gastroenteritis - prevention & control; Gastroenteritis - virology; Geometric mean; Hemagglutination Inhibition Tests; Homing; Humans; Immunoglobulins; Infectious diseases; Integrins; Lipid A - administration & dosage; Lipid A - analogs & derivatives; Lipid A - immunology; Lymphoid Tissue - metabolism; Lymphoid Tissue - virology; Major and Brief Reports; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Mucous Membrane - metabolism; Mucous Membrane - virology; Norovirus; Norwalk virus; Norwalk virus - immunology; Receptors, Lymphocyte Homing - metabolism; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral Vaccines - administration & dosage; Viral Vaccines - adverse effects; Viral Vaccines - immunology; Viral Vaccines - standards; Virology; Viruses; Young Adult; Virus; Infection; Calicivirus; Antibody; Norwalk like virus; Caliciviridae; Immunological adjuvant; Mucosa; Virus like particle; Vaccine; Intranasal administration; Lymphoid tissue
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1086/657087

Background. Noroviruses cause significant morbidity and mortality from acute gastroenteritis in all age groups worldwide. Methods.We conducted 2 phase 1 double-blind, controlled studies of a virus-like particle (VLP) vaccine derived from norovirus GI.1 genotype adjuvanted with monophosphoryl lipid A (MPL) and the mucoadherent chitosan. Healthy subjects 18–49 years of age were randomized to 2 doses of intranasal Norwalk VLP vaccine or controls 21 days apart. Study 1 evaluated 5-, 15-, and 50-μg dosages of Norwalk antigen, and study 2 evaluated 50-and 100-μg dosages. Volunteers recorded symptoms for 7 days after dosing, and safety was followed up for 180 days. Blood samples were collected for serological profile, antibody secreting cells (ASCs), and analysis of ASC homing receptors. Results. The most common symptoms were nasal stuffiness, discharge, and sneezing. No vaccine-related serious adverse events occurred. Norwalk VLP-specific immunoglobulin G and immunoglobulin A antibodies increased 4.8-and 9.1-fold, respectively, for the 100-μg dosage level. All subjects tested who received the 50-or 100-μg vaccine dose developed immunoglobulin A ASCs. These cells expressed molecules associated with homing to mucosal and peripheral lymphoid tissues. Conclusions. The intranasal monovalent adjuvanted Norwalk VLP vaccine was well tolerated and highly immunogenic and is a candidate for additional study. Trial Registration. ClinicalTrials.gov identifier: NCT00806962.