Measuring Responses to Sublingual Antigens - Full Text View

Sponsors and Collaborators:	St George's, University of London Commission of the European Union
Information provided by:	St George's, University of London
ClinicalTrials.gov Identifier:	NCT00949572

Purpose

This study is a preliminary investigation of immune responses to proteins ("antigens") taken up across the undersurface of the tongue. Animal studies have shown that this "sublingual" surface can take up antigens and stimulate immune responses, which may have a different character to responses induced by injecting the same antigens. In previous studies of nasal and oral delivery, we used licensed vaccine preparations as pure and well−characterised model antigens safe for use in humans. We will use a licensed "HPV" vaccine as the source of antigens in this study. The quantity and character of responses (lymphocyte number and pattern of surface proteins, concentration and type of antibodies in fluids) will be measured in detail in various anatomical sites (blood, vaginal secretions) before and after delivery of antigens on three occasions. As well as using established immune assays to characterise the responses, we will develop new research assays to detect populations of lymphocytes and antibodies present in secretions. To ensure we have positive samples to include in our assays and validate new techniques, we will recruit some subjects to receive a standard intramuscular injection, as this is known to be nearly 100% reliable in inducing measurable immune responses. As this is a preliminary study we will recruit enough subjects (based on our previous experience with nasal, oral and injected delivery) to ensure we generate sufficient responses we can measure. We may be able to draw some tentative conclusions about differences in character of immune responses following sublingual or injected delivery, but it is not the intention of this initial study to formally compare these two routes. If we observe that sublingual delivery in humans can induce immune responses, we can select assays to test any differences more formally in subsequent bigger and more focused studies.

Condition	Intervention
Sexually Transmitted Diseases, Viral	Biological: Human Papillomavirus 6,11,16,18 Vaccine Recombinant alum ads

Study Type:	Interventional
Study Design:	Basic Science, Non-Randomized, Open Label, Parallel Assignment
Official Title:	Characterisation of Human Disseminated Cellular and Humoral Immune Responses Following Sublingual or Intramuscular Deposition of Antigens

Resource links provided by NLM:

MedlinePlus related topics: Sexually Transmitted Diseases

Drug Information available for: Aluminum sulfate Alum, Potassium

U.S. FDA Resources

Further study details as provided by St George's, University of London:

Primary Outcome Measures:

Concentration and isotype profile of antigen-specific antibody in cervico-vaginal secretions measured by ELISA and/or LUMINEX assay [ Time Frame: 0, 1, 4 and 5 months after first immunization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Concentration and isotype profile of antigen-specific antibody in serum measured by ELISA and/or LUMINEX assay [ Time Frame: 0, 1, 4 & 5 months after first immunization ] [ Designated as safety issue: No ]
Frequency and isotype profile of antigen-specific antibody secreting cells in blood [ Time Frame: 0 and 1 week after each immunization ] [ Designated as safety issue: No ]
Frequency and expression profile of mucosa-associated homing, memory and regulatory markers on antigen-specific T cells in blood in response to in vitro antigen stimulation [ Time Frame: 0 and 4 weeks after each immunization ] [ Designated as safety issue: No ]
Profile of cytokine secretion by peripheral blood mononuclear cells in response to in vitro antigen stimulation measured by ELISA [ Time Frame: 0 and 4 weeks after each immunization ] [ Designated as safety issue: No ]

Estimated Enrollment:	18
Study Start Date:	September 2009
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Intramuscular administration: Experimental Intramuscular injection of HPV vaccine proteins	Biological: Human Papillomavirus 6,11,16,18 Vaccine Recombinant alum ads 1 intramuscular dose (0.5 ml) on month 0, 1 and 4 containing approximately: Human Papillomavirus Type 6 L1 protein 20 micrograms Human Papillomavirus Type 11 L1 protein 40 micrograms Human Papillomavirus Type 16 L1 protein 40 micrograms Human Papillomavirus Type 18 L1 protein 20 micrograms
Sublingual administration: Experimental Sublingual administration of HPV vaccine proteins	Biological: Human Papillomavirus 6,11,16,18 Vaccine Recombinant alum ads 1 sublingual application on month 0, 1 and 4 of 0.5 ml containing approximately: Human Papillomavirus Type 6 L1 protein 20 micrograms Human Papillomavirus Type 11 L1 protein 40 micrograms Human Papillomavirus Type 16 L1 protein 40 micrograms Human Papillomavirus Type 18 L1 protein 20 micrograms

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

A female adult volunteer aged between 18 and 35 years old.
Subjects who the investigator believes can and will comply with the requirements of the protocol.
Provide written informed consent following a detailed written explanation of participation in the protocol.
They are in good health as determined by medical history, physical examination, haematology testing, and clinical judgement before entering into the study.
They are available for the whole duration of the study.
If of childbearing potential, must have a negative pregnancy test before each immunisation.
They have not donated blood during 3 months prior to study entry and agree to not donate for 3 months after the end of their participation in the study.
They are eligible for free medical treatment

Exclusion Criteria:

They have already been vaccinated with an HPV vaccine
They have participated in a clinical trial in the last 6 months in which they have been exposed to an investigational product (pharmaceutical product or placebo or device) or concurrent participation in another clinical research study at the time of enrolment.
Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the first dose of challenge agent, or planned use during the study period.
They are pregnant or breast-feeding.
They have a known or suspected ongoing cervico-vaginal disease, malignancy or abnormality discovered at time of screening.
They present in the samples obtained at the screening visit: positive results for HIV, HBs Ag, anti-HBc and anti-HCV antibody, a clinically significant abnormality in haematology. Normal ranges will be defined by the pathology laboratory undertaking assays.
They have a clinically significant acute or chronic pulmonary, cardiovascular, hepatic or renal functional abnormality, blood or neurological disorders, immune dysfunction, autoimmune diseases, diabetes (excluding history of gestational diabetes), or malignancy at the time of enrolment, as determined by medical history, physical examination or laboratory screening tests.
They have received any form of immunosuppressive therapy in the past 6 months.
They are receiving any medications via vaginal route (as this may interfere with collection of samples).
They have any tongue or frenulum piercings or oral jewellery that may interfere with sublingual delivery.
They have received blood products or immunoglobulins 120 days prior to enrolment.
They have thrombocytopaenia or any coagulation disorder (because bleeding may occur following an intramuscular administration in these individuals).
Any other medical, psychiatric or social condition, drug treatment, occupational or other responsibility that, in the judgement of the investigator, would interfere with or serve as a contradiction to adherence to the study protocol or ability to give informed consent.
Individuals who cannot read or speak fluent English.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00949572

Contacts

Contact: David JM Lewis, MD	+44 2087255826	d.lewis@sgul.ac.uk
Contact: Elka Giemza	+44 2087252316	rgiemza@sgul.ac.uk

Locations

United Kingdom, England
St George's Vaccine Institute, St George's University of London
London, England, United Kingdom, SW17 0RE

Sponsors and Collaborators

St George's, University of London

Commission of the European Union

Investigators

Principal Investigator:

David JM Lewis, MD

St George's, University of London

More Information

Additional Information:

Website of St George's Vaccine Institute This link exits the ClinicalTrials.gov site

Website of St George's University of London This link exits the ClinicalTrials.gov site

European Commission EURONEUT41 funding body website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	St George's, University of London ( David J.M. Lewis / Principal Investigator )
Study ID Numbers:	SG09-EN01, REC number: 09/80803/77, EC grant number 201038
Study First Received:	July 29, 2009
Last Updated:	July 29, 2009
ClinicalTrials.gov Identifier:	NCT00949572 History of Changes
Health Authority:	United Kingdom: Research Ethics Committee

Keywords provided by St George's, University of London:

mucosal immunity
immunization
sublingual

Study placed in the following topic categories:

Genital Diseases, Female
Virus Diseases
Sexually Transmitted Diseases, Viral

Aluminum sulfate
Sexually Transmitted Diseases
Genital Diseases, Male

Additional relevant MeSH terms:

Genital Diseases, Female
Virus Diseases
Sexually Transmitted Diseases, Viral

Sexually Transmitted Diseases
Genital Diseases, Male
Infection

ClinicalTrials.gov processed this record on September 11, 2009