Robust mucosal-homing antibody-secreting B cell responses induced by intramuscular administration of adjuvanted bivalent human norovirus-like particle vaccine
| Autor: | Sharon E. Frey, David J. Topham, Robert L. Atmar, Jennifer Ferreira, Aarthi Sundararajan, Paul M. Mendelman, Wilbur H. Chen, Mark Y. Sangster, Robert F. Bargatze, John J. Treanor |
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| Rok vydání: | 2015 |
| Předmět: |
Male
viruses Monophosphoryl Lipid A CD38 Antibodies Viral medicine.disease_cause Placebos B-Lymphocytes B cell Mucosal biology Immunogenicity virus diseases Middle Aged Treatment Outcome medicine.anatomical_structure Infectious Diseases Molecular Medicine Female Antibody Adult Adolescent Injections Intramuscular Peripheral blood mononuclear cell Young Adult Adjuvants Immunologic Double-Blind Method Antigen Immunology and Microbiology(all) medicine Animals Humans Vaccines Virus-Like Particle Immunity Mucosal General Veterinary General Immunology and Microbiology business.industry Norovirus Public Health Environmental and Occupational Health Viral Vaccines Virology veterinary(all) Immunoglobulin A Immunoglobulin G Immunology biology.protein Immunization business Vaccine |
| Zdroj: | Vaccine. 33(4):568-576 |
| ISSN: | 0264-410X |
| DOI: | 10.1016/j.vaccine.2014.09.073 |
| Popis: | Background Two major antigenically heterogenous norovirus genogroups (GI and GII) commonly infect humans and are the leading cause of foodborne, viral gastrointestinal infections in adults. Methods We assessed B cell responses in participants in a double-blind, placebo-controlled, dose-escalation phase 1 study of the safety and immunogenicity of an intramuscular bivalent norovirus virus-like particle (VLP) vaccine. The vaccine contained a GI.1 VLP (Norwalk) and a consensus GII.4 VLP, representing the two major genotypes that cause human disease, and was administered on days 0 and 28 to healthy adults aged 18–49 years. Four separate cohorts received increasing doses of 5 μg, 15 μg, 50 μg, and 150 μg of each VLP adjuvanted in monophosphoryl lipid A and alum. PBMCs were analyzed for B cell activation and mucosal homing markers (flow cytometry) and VLP-specific and total IgG and IgA Ab-secreting cells (ASCs); and serum titers of VLP-specific IgG, IgA, and Pan-Ig were determined. Results The vaccine elicited CD27+ CD38+ plasmablasts and high frequencies of ASCs specific for both VLP antigens in the peripheral blood at 7 days after the first dose. The plasmablasts exhibited a mucosal-homing phenotype and included a high proportion of IgA ASCs. Serum antibodies increased as early as 7 days after the first immunization. Conclusions The data suggest that a single dose of the IM bivalent norovirus vaccine is effective in activating pre-existing B cell memory. The rapid B cell response and the mucosal homing phenotype of induced ASCs are consistent with anamnestic responses in subjects primed by prior oral norovirus infection. This study is registered at ClinicalTrials.gov Identifier NCT01609257 . |
| Databáze: | OpenAIRE |
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