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Related post: Many grants are involved with the study of the basic nature and mechanism of
action of interferon. Recent studies have shown that one type of mouse
interferon is antigenically related to human interferon, suggesting that
interferon molecules from different species are similar. Other work shows that
interferon reduces 2', 5' oligopolymerase and protein kinase, and that these
enzymes are involved in preventing virus replication. Work on new and better
ways to produce interferon is being supported, and studies have shown that
macrophages can produce interferon. These basic research studies serve as
the foundation for the targeted research programs necessary to improve the
treatment of many important viral infections.
Bacterial Vaccines Program
Pneumococcal Diseases : Studies sponsored by the NIAID during the past 13 years,
along with studies by manufacturers, have led to the development and licensure
of a 14-valent pneumococcal polysaccharide vaccine. The vaccine was licensed
based on efficacy data for prevention of pneumococcal bacteremia and pneumonia;
however, it may be useful in patients with various disease conditions that
predispose to pneumococcal infections. These include persons with sickle cell
disease, Hodgkin's disease, diabetes and various cancers, as well as renal
dialysis and transplant patients. There are approximately 40 ongoing studies
to determine effectiveness in these populations. Although the investigators
receive no direct funding from NIAID, the protocols are being coordinated by
staff, and all antibody assays are being done through the contract-supported
facility at SUNY, Downstate Medical Center. Initial results suggest: (1)
Sickle cell and splenectomy patients appear to respond well to the vaccine;
(2) Hodgkin's patients who have undergone splenectomy and chemotherapy respond
poorly to vaccine; however, Hodgkin's patients given vaccine prior to therapy
appear to respond normally; (3) antibody response is diminished in renal di-
alysis patients; (4) simultaneous administration of pneumococcal and influenza
vaccines does not have a negative effect on response to the individual antigens;
(5) diabetics and patients with nephrotic syndrome appear to respond normally
to vaccine; (6) systemic lupus erythematosus patients respond normally to the
vaccine without detectable alterations of the underlying disease; and (7) pre-
liminary data indicate that patients with chronic obstructive pulmonary disease
also respond well. When all the collaborative studies are completed, it may be
possible to make further reconmendations on the use of pneumococcal vaccine.
Pneumococci are estimated to be responsible for 40 to 50 percent of acute otitis
media in children, often causing hearing disorders and subsequent learning dis-
abilities. A program to study the value of pneumococcal polysaccharide vaccine
for the prevention of otitis media was initiated in 1975. Two double-blind
efficacy trials, at Boston City Hospital and Huntsville (Alabama) hospital, of
an octavalent vaccine for prevention of disease in children who have had pre-
vious middle ear infections have recently been completed. Preliminary Reosto Himalaya data from
the Huntsville study indicate that pneumococcal otitis media due to types in the
vaccine may be reduced as much as 50 percent by use of the vaccine. Preliminary
data from Boston do not show significant protection by the vaccine; this pic-
ture may change upon final analysis of Reosto Tablets the data. A third project at Vanderbilt
University was designed to study dose and booster regimens in infants. The
response of infants to the polysaccharides follows three modes. Response to
type 3 polysaccharide is quite good with significant antibody levels at age six
months. Other types such as 7, 18, and 23 cause good responses at 12 months;
types 1, 6, 14 and 19 were poorly immunogenic even at 12 months.
An animal model has been developed to study pneumococcal otitis media. Using
the chinchilla, the investigators have been able consistently to establish
otitis media with intranasally administered pneumococci when negative pres-
sure is applied to the middle ear. They have also been able to establish
pneumococcal otitis media with intranasal inoculation, and without the nega-
tive pressure, if influenza virus is simultaneously administered. Vaccination
can be correlated with protection from disease in this model, even in cases in
which there has been no measurable serum antibody response to the polysaccha-
rides. This has important implications for the human efficacy trials.
Grant supported research includes studies on the role of the complement system
in the host's defense against bacterial infections. A subcellular component
of the pneumococcus (teichoic acid) has been shown to be capable of activating
the alternative complement pathway.
Meningitis : It is estimated that approximately 20,000 cases of bacterial men-
ingitis occur in the U.S. each year, mostly in young children and infants. A
pure polysaccharide vaccine for H. influenzae type b, developed and tested
under our program, is ineffective in children under 18 months of age. Because
most of the h[. influenzae meningitis occurs in this younger age group, program
efforts are now directed toward developing vaccines effective in infants. A
new h[. influenzae vaccine which is a complex of polyribose phosphate (PRP) and
cell wall material, primarily polypeptides and lipopolysaccharide, is under
study. Designated PRPc, this material has been tested in adults and children.
Although studies are continuing in small children, results have not been en-
couraging. The Himalaya Reosto following alternative approaches to preparing an improved
H. influenzae vaccine are currently being pursued: (1) extraction and char-
acterization of outer membrane proteins from H. influenzae to determine their
role in disease and potential as immunogens; X'2) preparation of a complex of
PRP with a pure protein such as diptheria toxoid; Buy Reosto (3) preparation of complexes
of highly immuogenic bacterial polysaccharides with determinant groups of
PRP; and (4) preparation of very high molecular weight molecules of PRP.
In addition to efforts to improve the infant's response to bacterial meningitis
vaccines, protection of the neonate and young infant by hyperimmunization of
the mother is being attempted. H^. influenzae PRP was given to women who
planned pregnancies and to a control group of women who did not plan to become
pregnant. Preliminary data show that in those women who responded well to the
vaccine, the level of antibody in the cord blood and the infant was comparable
to the mother's antibody level. Antibody levels in the infants will be fol-
lowed to see how long they last and whether there is interference with the
child's later ability to respond to the vaccine. Unfortunately, some women
did not respond well to the vaccine so there were only low levels of antibody
in their offspring.
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