Acute otitis media (OM) and OM with effusion are common childhood diseases. Otitis media is
a condition marked by inflammation of the middle ear. Otitis media with effusion typically
means a long-term (chronic) middle ear inflammation with secretion of fluid into the middle
ear due to the blockage of the canal leading from the middle ear to the mouth (eustachian
tube). The fluid involved can be sterile (no organisms) or infected with disease causing
organisms, such as bacteria or viruses.
Nontypeable Haemophilus influenzae (NTHi) is a bacteria that is one of the leading causes of
OM and respiratory infections in older people. NTHi carry substances on their surface
called antigens. When antigens come into contact with the right kinds of cells in the body,
an immune reaction is caused. This reaction is often the symptoms of sickness that a
patient feels. One of the major antigens on the surface of NTHi is called
In order for the body to fight off the attack of antigens, it creates substances called
antibodies. Antibodies counter the action of antigens and make the bacteria harmless.
However, the immune system must learn how to make the right antibodies for the right
antigens. This is done by giving vaccines.
Vaccines can contain a small amount or an inactive form of an antigen. Once the immune
system recognizes the antigen it can start making antibodies to prevent sickness if it is
ever exposed to the antigen again. Presently there are no vaccines for NTHi.
One of the reasons why there is no vaccine for NTHi is because the antigen, LOS, is very
toxic when given to humans. Researchers have tried to make the antigen less dangerous by
removing the toxic effects. It is referred to as dLOS. Unfortunately, dLOS is unable to
start antibody production.
However, researchers have found that by combining dLOS with another vaccine for tetanus
(tetanous toxoid), they were able to stimulate the immune system to create antibodies in
laboratory animals. These laboratory animals were protected against NTHi infections and
otitis media (OM).
Researchers would like to test the effectiveness and safety of dLOS-TT vaccine in adult
humans. Their ultimate goal is to develop a vaccine for OM and respiratory infections
caused by NTHi.
Acute otitis media (OM) and OM with effusion are common childhood diseases. Nontypeable
Haemophilus influenzae (NTHi) is a leading cause of OM and respiratory infections in older
individuals. Currently, there is no vaccine for NTHi infection. Studies indicate that
serum bactericidal antibodies are associated with protection from NTHi infection. We
predict that serum antibodies with bactericidal activity to the lipooligosaccharide (LOS), a
major surface antigen and virulence factor of NTHi, will confer immunity to this pathogen.
LOS of NTHi is too toxic to administer to humans and detoxified LOS (dLOS) is not
immunogenic, probably due to its low molecular weight. In order to improve its
immunogenicity, the dLOS was convalently bound to tetanus toxoid (TT) using a clinically
relevant scheme of vaccination, elicited bactericidal antibodies to LOS in an in vivo model.
This investigational vaccine also showed protection against infection in a chinchilla
otitis media model. We propose to evaluate the safety and immunogenicity of this dLOS-TT
vaccine in adults (Phase I). Our goal is to develop a vaccine for OM and respiratory
infections caused by NTHi.
Healthy volunteers between ages 18 and 35 years.
Not pregnant or planning to become pregnant in next six months.
Hepatitis B Negative.
No chronic Respiratory Tract Infections.
No history of abnormal immune system.
No severe or multiple allergies.