Immunogenicity and Safety of Live Attenuated Influenza Vaccine (Flumist) Administered by Nasal and Sublingual Route
Information source: International Vaccine Institute
Information obtained from ClinicalTrials.gov on December 08, 2011
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: Influenza vaccine (Biological); Influenza vaccine (Biological)
Phase: Phase 1
Sponsored by: International Vaccine Institute
Official(s) and/or principal investigator(s):
Kyung-Sang Yu, M.D., Principal Investigator, Affiliation: Seoul National University Hospital
Cecil Czerkinsky, Ph.D., Principal Investigator, Affiliation: International Vaccine Institute
SeungHwan Lee, M.D., Phone: +82 220721666, Email: email@example.com
Background: It is well established that live attenuated organisms can be highly effective
vaccines, immune responses elicited can often be of greater magnitude and of longer duration
than those produced by non-living antigens and are often able to confer protection after a
single dose. Unlike killed influenza vaccine preparations injected by the parenteral route,
live influenza vaccines are able to induce potent secretory (mainly IgA) antibody responses
in the airway mucosae and can also evoke cell mediated responses. T cell proliferation,
cytokine production, cytotoxic T cell responses and antibody-dependent cell cytotoxicity
have all been elicited by live attenuated vaccines.
There has been a history of the use of live attenuated flu vaccines as safe and effective
vaccines for the prevention of flu in animals and humans. Live-attenuated cold-adapted
influenza vaccines have been proved to be highly efficacious to protect against clinical fly
symptoms. Among these, FluMist, a nasal vaccine formulation developed by Medimmune Inc, has
been approved by the US FDA. Recent side by side clinical trials have demonstrated that this
nasal vaccine was significantly superior to conventional killed flu vaccine in protecting
against flu symptoms.
Sublingual administration of live influenza virus at a dose lethal by the nasal route was
well tolerated and did not redirect virus to the olfactory bulb. In addition, in a recent
Phase I clinical study (NCT00820144) conducted in France, the sublingual administration of
rCTB (up to 1 mg) in healthy adult volunteers was found to be safe.
A major issue has arisen regarding the ease with which vaccines could be administered to
young children, especially infants, and to elderly subjects in whom nasal vaccination has
not been possible and/or approved due to difficulties of administering nasal vaccines in
infants and to undesired side effects related to frequent rhinitis and sneezing episodes in
elderly subjects. This study is designed to investigate the safety, tolerability and
immunogenicity of a new route of administration of vaccines, using the nasal FluMist
formulation as prototype vaccine.
Objectives: To evaluate the immunogenicity and safety of a nasal and sublingual influenza
virus vaccine (FluMist) in healthy adult volunteers
Study design: This will be a randomized study on a total 40 subjects; each 20 subjects will
receive vaccine via nasal and sublingual route, respectively
Official title: A Controlled Study to Determine the Immunogenicity and Safety of Cold-adaptive Live Attenuated Influenza Vaccine (Flumist) Administered by the Nasal and Sublingual Route in Healthy Adult Volunteers
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: Subjects will be considered to have achieved sero-protection if their serum titer is equal to or more than 40 as determined by means of the Passive Haemagglutination inhibition titer.
Blood IgG and IgA-antibody secreting cell number to flu virus
Virus neutralization serum titer
Secretory antibody titer
Cell mediated immune responses
The proportion of subjects reporting adverse events, attributable to the study medication during the study
Minimum age: 20 Years.
Maximum age: 49 Years.
- Healthy volunteers who are able and willing to give informed consent, following a
detailed explanation of participation in the study.
- Volunteers who will be available for the duration of the study and available for
scheduled and potential additional visits
- Subjects with any clinically significant medical or psychiatric condition or
clinically significant abnormal serum biochemistry or haematology results that, in
opinion of the Investigator, preclude participation in the study.
- Female subjects who are pregnant (using urine test) or breast-feeding, or of
childbearing potential and unwilling to use a reliable method of contraception (e. g.
oral contraceptives or contraceptive during sexual activities such as a condom,
contraceptive diaphragm, intrauterine device, hormonal contraceptive, or intercourse
with a male partner who has had a vasectomy etc.) throughout the study period.
- Subjects who have known airway hypersensitivity to one of Flu vaccine excipients
within 14 days prior to administration of study medication.
- Subjects who have known buccal hypersensitivity to any component of the vaccine or
buffer solution used in this study, including subjects with phenylketonuria.
- Subjects with direct contact with at risk groups (e. g. patients in special care
units, immuno-compromised individuals, pregnant women, children under 2 years of age
and individuals over 70 years).
- Subjects with a known impairment of immune function including seropositive for HIV or
those receiving (or have received in the 6 months prior to study entry) cytotoxic
drugs immunosuppressive therapy (including systemic corticosteroids).
- Subjects with a significant acute febrile illness (fever of 38. 0 Celsius degree or
more) at time of dosing.
- Subjects who have chronic diseases: Chronic diseases will include all autoimmune and
immuno-compromising conditions and any other chronic condition, which at the
judgement of the Investigator, may put the subject at higher risk of side effects
from the study vaccine. Conditions in the latter category might include unexplained
anaemia, hepato-biliary disease, uncontrolled hypertension, subjects with prosthetic
joints or heart valves, etc.
- Subjects with a current problem, based on history, with substance abuse or with a
history of substance abuse
- Subjects who are currently involved in a clinical trial, have taken an
investigational drug or have received investigational or licensed vaccines in the
preceding 4 weeks or anticipate receiving a vaccine other than study medication
during the first 4 weeks of the study
- Subjects who have known hypersensitivity to eggs or egg proteins
- Subjects who have chronic respiratory infections or syndromes
- Unable to receive oral (sublingual) administration.
- Receiving anti-viral agents.
- Subjected to contraindications and/or precautions described in drug information
Locations and Contacts
SeungHwan Lee, M.D., Phone: +82 220721666, Email: firstname.lastname@example.org
Seoul National University Hospital, Seoul 110744, Korea, Republic of; Recruiting
Starting date: December 2011
Last updated: December 6, 2011