Dataset Information

Adjuvanted intranasal Norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues.

ABSTRACT:

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.

SUBMITTER: El-Kamary SS

PROVIDER: S-EPMC3722871 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Publications

Adjuvanted intranasal Norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues.

El-Kamary Samer S SS Pasetti Marcela F MF Mendelman Paul M PM Frey Sharon E SE Bernstein David I DI Treanor John J JJ Ferreira Jennifer J Chen Wilbur H WH Sublett Richard R Richardson Charles C Bargatze Robert F RF Sztein Marcelo B MB Tacket Carol O CO

The Journal of infectious diseases 20101027 11

<h4>Background</h4>Noroviruses cause significant morbidity and mortality from acute gastroenteritis in all age groups worldwide.<h4>Methods</h4>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 ...[more]

PMID: 20979455

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Project description:Mucosal immune responses are crucial in protecting against pathogens entering through mucosal surfaces. However, due to poor T-cell responsiveness upon mucosal antigenic stimulation, mucosal immunity remains difficult to obtain through vaccines and requires appropriate adjuvants. We previously demonstrated that administered systemically to healthy macaques or locally expressed in the intestinal mucosa of acutely SIV-infected macaques, interleukin-7 (IL-7) triggers chemokine expression and immune cell homing into mucosae, suggesting its important role in the development of mucosal immune responses. We therefore examined whether local delivery of recombinant glycosylated simian IL-7 (rs-IL-7gly) to the vaginal mucosa of rhesus macaques could prepare the lower female genital tract (FGT) for subsequent immunization and act as an efficient mucosal adjuvant. First, we showed that local administration of rs-IL-7gly triggers vaginal overexpression of chemokines and infiltration of mDCs, macrophages, NKs, B- and T-cells in the lamina propria while MamuLa-DR+ APCs accumulated in the epithelium. Subsequent mucosal anti-DT immunization in macaques resulted in a faster, stronger, and more persistent mucosal antibody response compared to DT-immunization alone. Indeed, we detected robust productions of DT-specific IgAs and IgGs in their vaginal secretions and identified cells secreting DT-specific IgAs in their vaginal mucosa and IgGs in draining lymph nodes. Finally, the expression of chemokines involved in the organization of tertiary lymphoid structures (TLS) was only increased in the vaginal mucosa of IL-7-adjuvanted immunized macaques. Interestingly, TLSs developed around PNAd+ high endothelial venules in their lower FGT sampled 2 weeks after the last immunization. Non-traumatic vaginal administration of rs-IL-7gly prepares the mucosa to respond to subsequent local immunization and allows the development of a strong mucosal immune response in macaques, through the chemokine-dependent recruitment of immune cells, the activation of mDCs and the formation of TLSs. The localization of DT-specific IgA+ plasma cells in the upper vaginal mucosa argues for their contribution to the production of specific immunoglobulins in the vaginal secretions. Our results highlight the potential of IL-7 as a potent mucosal adjuvant to stimulate the FGT immune system and elicit vaginal antibody responses to local immunization, which is the most promising way to confer protection against many sexually transmitted diseases.

Dataset Information

Adjuvanted intranasal Norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues.

Background

Methods

Results

Conclusions

Publications

Adjuvanted intranasal Norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues.

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