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The Journal of Infectious Diseases 2010;202:1649?1658
? 2010 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2010/20211-0006$15.00
DOI: 10.1086/657087
MAJOR ARTICLE
Adjuvanted Intranasal Norwalk Virus‐Like Particle Vaccine Elicits Antibodies and Antibody‐Secreting Cells That Express Homing Receptors for Mucosal and Peripheral Lymphoid Tissues
Samer S. El‐Kamary,1,2,a
Marcela F. Pasetti,2,a
Paul M. Mendelman,4
Sharon E. Frey,5
David I. Bernstein,6
John J. Treanor,7
Jennifer Ferreira,7
Wilbur H. Chen,2
Richard Sublett,4
Charles Richardson,4
Robert F. Bargatze,4
Marcelo B. Sztein,2 and
Carol O. Tacket2
1Department of Epidemiology and Public Health, 2Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, and 3The EMMES Corporation, Rockville, Maryland; 4LigoCyte Pharmaceuticals, Inc, Bozeman, Montana; 5Saint Louis University School of Medicine, St Louis, Missouri; 6Cincinnati Children?s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio; 7University of Rochester Medical Center, Rochester, New York
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.
? 2010 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2010/20211-0006$15.00
DOI: 10.1086/657087
MAJOR ARTICLE
Adjuvanted Intranasal Norwalk Virus‐Like Particle Vaccine Elicits Antibodies and Antibody‐Secreting Cells That Express Homing Receptors for Mucosal and Peripheral Lymphoid Tissues
Samer S. El‐Kamary,1,2,a
Marcela F. Pasetti,2,a
Paul M. Mendelman,4
Sharon E. Frey,5
David I. Bernstein,6
John J. Treanor,7
Jennifer Ferreira,7
Wilbur H. Chen,2
Richard Sublett,4
Charles Richardson,4
Robert F. Bargatze,4
Marcelo B. Sztein,2 and
Carol O. Tacket2
1Department of Epidemiology and Public Health, 2Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, and 3The EMMES Corporation, Rockville, Maryland; 4LigoCyte Pharmaceuticals, Inc, Bozeman, Montana; 5Saint Louis University School of Medicine, St Louis, Missouri; 6Cincinnati Children?s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio; 7University of Rochester Medical Center, Rochester, New York
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.
