istorie stafilococ
Post on 03-Jun-2018
223 Views
Preview:
TRANSCRIPT
-
8/12/2019 Istorie Stafilococ
1/19
VACCINE RESEARCH NTERNATIONAL PlcVACCINE RESEARCH NTERNATIONAL Plc
STAPHYLOCOCCAL VACCINES
Ahmad A; Davies JA; Ravenhill KA and Skinner GRB
-
8/12/2019 Istorie Stafilococ
2/19
Staphylococcal infection
A hospital acquired infection
In UK, Staphylococcal infections account for about one fifth ofHospital Acquired Infections.
Staphylococci cause post-operative infections, septicaemia,cellulitis, pneumonia and osteomyelitis and are extremelytroublesome with intra-vascular devices and catheters.
Approximately 40% are due to the antibiotic-resistant strain ofStaphylococcus aureus, MRSA.
Similar problems exist in Europe, the USA and Japan.
-
8/12/2019 Istorie Stafilococ
3/19
Hospital acquired infections
PROBLEM COSTS
UK 100,000 patients infected per yearof whom an estimated 5000 die.
1bill ion per year
USA 2 mill ion patients infected per year.10% die; approx. 14,000 die fromdrug-resistant organisms.
> $4.5 bil lion peryear
-
8/12/2019 Istorie Stafilococ
4/19
MRSA
A current threat to public health
worldwide
Resistance emerging to vancomycin
MRSA now entering the general community.
A worldwide problem e.g. 70% of staphylococcalinfections in Japan are MRSA.
-
8/12/2019 Istorie Stafilococ
5/19
STAPHYLOCOCCAL VACCINES
McCoy and Kennedy
1960
Autologous vaccine
inactivated with
benzalkonium chloride
Intracutaneous
injections 2-3
days apart.
Total of 10
injections
Recurrent skin
infections,
osteomyelitis, post
operative wound
infections
44/60 Excellent
improvement
11/60 Improvement
5/60 Failure
Angyal et al 1967 Autovaccine*
Diffuse Smith strain of
S.aureus*
Compact Smith strain of
S.aureus*
Commercial polyvalent
vaccine
Intracutaneous
injections.
5 doses at 3-4
day intervals,
1-2 more ifneeded.
Recurrent
Staphylococcal skin
infectiuons in miners
eg furunculosis
12/13 Recovered
15/15 Recovered
0/12 Recovered
3/9 Recovered
-
8/12/2019 Istorie Stafilococ
6/19
STAPHYLOCOCCAL VACCINES
Salmon & Symonds
1963
Staphylococcal
bacteriophage lysate
Intranasal and in
children
-
8/12/2019 Istorie Stafilococ
7/19
STAPHYLOCOCCAL VACCINES
Greenberg et al 1961 Polyvalent somatic
antigen vaccine;
mixture of dornase
lysed strains of
S.aureus
Intracurtaneous and
intramuscular
Initial human tests
induced reaction after
inoculation.
Vaccine modified by
change in growth
medium
Dillenberg & Waldron
1963
Polyvalent somatic
antigen vaccine
Intramuscular
injections; 2 doses at
6 week intervals
Impetigo Reduction in
incidence of boils and
impetigo in 90% of
vaccinated
individuals in placebocontrolled study
-
8/12/2019 Istorie Stafilococ
8/19
STAPHYLOCOCCAL VACCINE
Mudd et al 1962 Divasta-Institut
Pasteur: purified
alpha toxoid +
inactivated
Staphylococci
Sclavo:
Staphylococcal
toxoid
Connaught
Laboratories:
Staphylococcal alpha
and beta toxoid
Lederle:
Staphylococcal
toxoid
formaldehyde treated
exotoxin
Subcutaneous andintramuscularinjections
Staphylococcalinfection andvolunteers
Rise in anti-alpha
toxin antibodies in all
vaccinated
individuals
-
8/12/2019 Istorie Stafilococ
9/19
-
8/12/2019 Istorie Stafilococ
10/19
STAPHYLOCOCCAL VACCINE
Rossi & Candiani
1983
Killed heptavalant
vaccine
Intramuscular
injections. 2 doses 2
days apart of high
antigen content
vaccine +Pseudomonas
aeruginosa vaccine
given at the same
time
Wound infections in
burns
Reduction in burn
infections but no
significant reduction
in septicaemias
-
8/12/2019 Istorie Stafilococ
11/19
STAPHYLOCOCCAL VACCINE
Weber et al 1971 Staphypan Berna:
formalin-inactivated
alpha toxin from
S.aureus + formalin-
inactivated endotoxinfrom S.epidermidis +
heat and formalin
inactivated S.aureus
and S.epidermidis in
0.01% Thiomersal
Subcutaneous
injections every 3
days 2-3 weeks prior
to surgery to allow
optimal antibodylevels to coincide
with operation
Prevention of infection of
prosthetic hip replacement
863 patients
1967-1970.
Infection rate
reduced from
6.8% to 0.45%
Scatizzi et al 1988 Staphypan Berna 6 intramuscular
injections of
increasing
concentration on
alternative days.
Booster every 1-3
months
Prevention of infection in
continuous ambulatory
peritoneal dialysis patients
20/22 No
S.aureus
peritonitis
1/20
S.epidermidis
peritonitis
22/22 No
catheter related
Staphylococcal
infection
-
8/12/2019 Istorie Stafilococ
12/19
STAPHYLOCOCCAL VACCINE
Poole-Warren et al
1991
Staphypan Berna 6 intramuscular
injections of
increasing
concentration over 6
weeks. 4 Boostersevery 3 months
Prevention of
infections in
continuous
ambulatory peritoneal
dialysis
124 patients. No
difference in
peritonitis or catheter
related
Staphylococcalinfection between
vaccinated and
placebo controlled
patients
-
8/12/2019 Istorie Stafilococ
13/19
STAPHYLOCOCCAL VACCINE
Welch et al 1996 Capsular
polysaccharide type
5 conjugated to
recombinant
Pseudomonasaeruginosa
exoprotein A
2 Intramuscular
injections at 6 week
intervals.
17 patients
24 Normal controls
Immune response in
human subjects
Increase in IgM and
IgG, declining by
35% in 6 months in
patients and 9% in
normal controls.
Nasal carriage of
S.aureus reduced
from 8/17 to 3/13 in 6
months
Shinefield et al 2002 Capsular
polysaccharide type
5 and 8 conjugated to
recombinant
Pseudomonas
aeruginosa exotoxin
A
Single intramuscular
injection
Double blind placebo
controlled trial in
patients with end
stage renal disease
Increase in antibody
levels against
capsular
polysaccharide types
5 and 8 in vaccinated
patients.
Reduction in
S.aureus
bacteraemias in
vaccinated patients
up to 40 weeks post
vaccination
-
8/12/2019 Istorie Stafilococ
14/19
VRI STAPHYLOCOCCAL VACCINE
ISOLATE
1. Staphylococcus aureus P/DFO75
2. Isolate from the peritoneal fluid of a CAPD patient with peritonitis
3. S.aureus P/DFO 75 is positive for collagen-binding protein, fibronectin-bindingprotein, fibrinogen-binding protein
VACCINE
The vaccine is prepared by chloroform-inactivation of a liquid culture of S.aureus
P/DFO 75. The bacteria are washed after treatment and the inactivated whole
bacteria constitute the vaccine preparation.
-
8/12/2019 Istorie Stafilococ
15/19
Immunoblot using S.aureus P/DFO 75 vaccine and sera from rabbit given the vaccine at a
concentration of 5X10 tenth bacterial equivalent
-
8/12/2019 Istorie Stafilococ
16/19
Immunoblot using S.aureus P/DFO 75 vaccine and sera from rabbit given the vaccine at a
concentration of 5X10 ninth bacterial equivalent
-
8/12/2019 Istorie Stafilococ
17/19
Immunoblot using S.aureus P/DFO 75 vaccine and sera from rabbit given the vaccine at a
concentration of 5X10 eighth bacterial equivalent
-
8/12/2019 Istorie Stafilococ
18/19
Reactivity of sera from femal e rabb it 19 given 5X10tenth Batch 5 vaccine (plateXX)
11.3.2004
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 2 4 6 8
Log d ilution sera
Absorban
ce
5X10tenth Pre (19)
5X10tenth I (19)
5X10tenth II (19)
5X10tenth III (19)
5X10tenth IV (19)
CONTROL
-
8/12/2019 Istorie Stafilococ
19/19
ACKNOWLEDGEMENTS
VACCINE MANUFACTURENORWEGIAN INSTITUTE OF PUBLIC HEALTH, OSLO, NORWAY
REGULATORY ADVISORSQUADRAMED, MIDHURST, WEST SUSSEX, UK
TOXICOLOGY
CTL, ALDERLEY PARK, MACCLESFIELD, CHESHIRE, UK
CLINICAL TRIALSIMBEC, MERTHYR TYDFIL, WALES, UK
BINDING PROTEIN EVALUATION
PROFESSOR JAN-INGMAR FLOCK, KAROLINSKA INSTITUTET,STOCKHOLME, SWEDEN
top related