SAFETY/EFFICACY
CONCERNS FOR
LYME VACCINE - LYMErix
Joel M. Shmukler,
Esquire
Lymecure
Online |
BACKGROUND
Lyme disease is a multi-systemic
infection caused by infection with the spirochetal bacteria, Borrelia
Burgdorderi. It is the most common vector borne illness in the United
States. It is one of the leading infectious diseases in the United
States. The actual incidence of lyme disease is unknown, but it is known
that the reported statistics which are based on surveillance criteria,
underreports the actual incidence of the disease by excluding known
cases which do not meet the criteria. Surveillance criteria are used
simply to get a sense of the rate of growth of an infection, not the
true incidence of it.
A recent study in NEJOM reported that
doctors routinely fail to report even cases that meet the surveillance
criteria because of cumbersome reporting procedures and a distaste for
paperwork. That study estimated this underreporting would result in 10
times more cases being reported than are currently reported. In
addition, misdiagnosis of the disease is prevalent, increasing the
impact of underreporting by an unknown factor. Almost 100,000 cases have
been reported to the CDC from 1982-1996. During that time the reported
incidence of the disease increased by at least 32 fold!
The disease has been reported in
almost all states, although certain regions of the country are
considered endemic, and some considered hyperendemic--there appear to be
geographic clusters of higher infection. Infection varies from state to
state, and even within states from county to county. While the
surveillance of the disease leaves a great deal to be desired, two
trends are clear--first, the incidence of the disease is increasing
rapidly; and, second, there appears to be a spread of the organism to
new areas.
LYMErix is a first generation,
recombinant OSPa based vaccine. It has a unique mode of action for
vaccines. It stimulates specific protective antibodies to be produced in
the person vaccinated against OSPa, immunogenicity (the process of
triggering protective antibodies). However, OSPa is not usually found in
the human host, and it is thought that the bacteria changes its outer
surface (triggered by heat) when moving from the tick vector to the
human, this is called "upregulation" and "antigenic
shifting."
So theoretically OSPa would not be a
good candidate for a vaccine in humans, in whom OSPa is not generally
found or detectable. It is thought that the mechanism of action is that
when a tick bites an infected host and consumes a blood meal where the
blood contains antibodies to OSPa that these antibodies kill the
bacteria in the midgut of the tick where OSPa is not only detectable,
but the dominant outer surface protein. Thus, the bacteria are killed
before transmission occurs. Theoretically.
I. EFFICACY ISSUES:
A. EFFICACY UNIMPRESSIVE/OVERSTATED
The commercials (that we have all
seen) for LYMERix state that the vaccine, like all vaccines, may not be
100% effective. That much is true. How effective is the vaccine? The
commercial, the literature and news reports have cited an 80% efficacy
rate in preventing "definite" and "aymptomatic" lyme
disease. However, if you include the category of "possible"
lyme disease as well, the overall efficacy rate is 68%. If you include
the category of "unconfirmed" lyme disease, in which the
vaccine has negative efficacy, or some percentage of those cases, the
efficacy rate is even lower, closer to 50%. The reported efficacy
figures depend upon a semantic/definitional game--by creating different
categories of vaccinees for the statistics Smith Kline has hidden the
overall poor efficacy of this vaccine. The category of
"unconfirmed" cases is the best example. The vaccine had
negative efficacy in these categories, and by excluding this category
they have effectively artificially inflated the efficacy numbers--a
disturbing number of people got sick with something but due to the
absence of laboratory confirmation Smith Kline did not count any of
these people as having gotten lyme, though they may have had every
symptom. Does this make sense when lyme is a clinical diagnosis? And,
perhaps this tells us something about people who don't develop a rash,
or detectable antibodies. Perhaps the vaccine is altering the natural
presentation of the disease. These unimpressive rates are only achieved
after the third shot, now schedulled a year after the first shot is
taken. Accelerated dosing schedules are in trials, but reliable data has
not been reported. (See tables 1 and 2).
It is interesting to note that the
Smith Kline study did prove that lyme disease is hyperendemic, and
seriously underreported. Vaccine recipients live(d) in endemic areas.
The group receiving vaccines and placebos showed per capita infection
rates in the study exceeding 1000 per 100,000, both in year 1 and year
2, even following vaccination!
Another interesting tidbit arose from
the study. While the data has not been published it has been presented
showing that 35-40% of people in both the Smith Kline study and the
Connaught study who developed lyme disease with confirmation by PCR
testing and/or culture, were negative by conventional serologic antibody
testing. In addition, there is obviously an additional percentage of
people without any laboratory evidence of lyme disease, who contracted
the disease--given the problems with all lyme testing, a known
population of seronegative patients, and the fact that the diagnosis of
lyme is ultimately a clinical one given the unreliability of the
testing.
B. EFFICACY ONLY ACHIEVED AFTER 3
SHOTS
After only 2 shots the efficacy rates
are even less impressive, 57% in preventing "definite" and
"asymptomatic" lyme disease. If you include the category of
"possible" lyme disease the overall efficacy rate is only 46%.
If you include the category of "unconfirmed" lyme disease, in
which the vaccine has negative efficacy, or some percentage of those
cases, the efficacy rates are even lower than that. So after shot 1 and
shot 2 and before getting shot 3 the benefits of the vaccine are
especially dubious, especially when weighed against safety concerns.
Until the third shot then, currently schedulled a year later, efficacy
is unimpressive, dubious at best. After the third shot efficacy rates
improve, however, protective antibodies begin to diminish quickly and we
know that a year after shot 3 (whenever given--even on accelerated
schedule) they have fallen to close to where they are after 2 shots, to
unimpresive levels of protection. (See table 2).
C. DURATION OF PROTECTION
UNCERTAIN/LIMITED
We know that the protection conferred
after 3 shots does not last, and Smith Kline has reported that
protective antibody levels drop to the level achieved after 2 shots in
less than a year after the third shot. So whatever protection is
conferred, diminishes quickly. So additonal booster shots will
definitely be needed, but the safety, efficacy and timing of such shots
has not been studied, tested or approved so safety and efficacy of
additional shots, which is of concern (additonal shots may trigger
problems, aggravate problems from previous shots). No FDA approval has
been sought or obtained for additonal shots. Data is being reported
anecdotally only by Smith Kline. They may not seek FDA approval for
boosters, instead relying on doctor's right to use approved medications
for "off label," (unapproved) uses.
D. BOOSTERS WILL BE
NEEDED/SAFETY/EFFICACY/TIMING NOT STUDIED/NOT APPROVED BY FDA
As stated above, additional booster
shots will be necessary following the 3rd shot. We do not know the
optimal timing, safety or efficacy of such shots, and such shots have
not been approved by the FDA. Safety and efficacy issues remain, and are
potentially more dramatic than the same issues after 3 shots only.
Safety concerns include additional boosters causing, aggravating
problems caused by the first 3 shots and perhaps remaining undetected. A
third booster could overwhelm the immune system, or overcome tolerances
to side effects that lasted through the first 3 shots. Nor do we know
whether additional boosters will provide the same level of protection as
the 3rd shot does. Why, knowing that boosters would be needed, did Smith
Kline seek approval based on studies that did not address these issues?
Perhaps they are aware of problems, frightened by what formal data may
show? The unanswered questions abound.
E. VACCINE DOES NOT PROTECT AGAINST
ALL STRAINS OF LYME
Lyme disease, caused by the bacteria
Borrelia Burdorferi, has exhibited genetic variations, known as strains.
While there are three major strains of lyme disease found in the world,
there are substrains by the hundreds. Limited research has been done but
strain variation has been associated with variant symptomatic
presentation. In the United States where one major strain is found,
almost 300 variant substrains have been identified. Smith Kline states
that the vaccine has not showed substantial variability in efficacy
against strains tested. How many strains have they tested? What safety
issues are involved with variant strains and the vaccine? Connaught,
which is developing a recombinant OSPa vaccine, similar to that which
Smith Kline is marketing, has recently entered into an agreement with
MedImmune to co-develop a vaccine based upon DbPa, to address the
problems of strain variation. The reports from MedImmune indicate that
OSPa is not protective against many "wild" strains found in
the field. It is thought that DbPa may protect against most/all strains.
Whether this is true or not, it is clear that OSPa is problematic in
this regard. Also, Smith Kline and Pasteur Meriux Connaugt (PMC) were in
a race to market with their OSPa vaccines for several years. One has to
wonder why Connaught has not sought final approval for their OSPa
vaccine? The studies have been finished for a long time. No new data is
being collected in trials. Has PMC abandoned their OSPa vaccine because
of safety and efficacy issues, not to mention lawsuits arising out of
the trials? Does the deal between PMC and MedImmune indicate that PMC
recognizes that OSPa vaccine is a failure (although maybe a good first
step in developing a vaccine that will be safe and effective in the
future).
F. VACCINE NOT EFFECTIVE IN PEOPLE
> 70 YEARS OF AGE
Older people were included in the
study but the vaccine proved to be less effective in them than 15-69
years old so the vaccine was not approved for use in this age group. It
is uncertain why this variant result occurred.
G. EFFICACY RATES MAY HAVE BEEN
INFLATED BY AWARENESS
Those who participated in the trials
were obviously aware of, and concerned about lyme disease (or they
wouldn't have volunteered for the trials--they were not paid). Part of
the study design called for vaccine recipient education--thus these
people may have taken more precautions than the ordinary person, thus
lowering infection rates overall. H. WERE ADVERSE EVENTS FAIRLY
REPORTED/DOCUMENTED: Both the Smith Kline and Connaught trials resulted
in the filing of a number of lawsuits. One of those suits alleged, among
other things, that adverse events were not promptly and honestly
reported to the FDA. Anecdotally, many participants who developed
illness reported that the doctors involved in the studies were
dismissive of their complaints, rather than thorough in evaluating the
question of whether an event was related or unrelated to vaccination.
II. SAFETY ISSUES:
A. PEOPLE WITH A PRIOR HISTORY OF LYME
MAY BE AT RISK
This may be the most serious
safety issue associated with the vaccine. The target group for this
vaccine is people who live in endemic areas. We know that these areas
feature high incidences of infection, including "asymptomatic"
infection, undiagnosed infection, and misdiagnosed infection. It is
impossible because of the unreliability of laboratory testing to screen
candidates for the vaccine for lyme disease effectively. People with a
recent history of lyme were excluded from the study. People with a more
remote history of simple infection were included, but comprised only a
small percentage of people in the study ( total of 11% self-reported
prior history--only 2% with serologic evidence for their prior lyme).
These people were not studied as a seperate high risk group but the
Smith Kline study does admit that people with a prior history of lyme
did suffer from a higher incidence of adverse effects from the vaccine.
These side effects were greater in number following the 2nd and then the
3rd shot. What the effect of additional booster shots will be is
unknown. Analytically it is obvious that the study design, and data
reported, deliberately glossed over this vital safety issue.
B. VACCINE NOT SAFE FOR CERTAIN
TISSUE TYPES
Two tissue types, HLA DR2 and HLA DR 4
have been specifically associated with a risk for chronic, destructive
arthritic symptoms caused by lyme. These seem to be unresponsive to
"adequate" antibiotic treatment, even when initiated promptly.
It is theorized that this is due to an autoiimune mechanism, triggered
by the infection, and likely because of molecular mimicry--the bacteria
shares certain genetic traits with our own tisse; antibodies formed to
attack the bacteria, attack our tissue. Similar associations have been
made with a smaller percentage of people with other tissue types as
well. Recently a specific mechansim for this autommunity has been
proposed, and documented, for people with the tissue type HLA DR4. There
is a link between OSPa and this mechanism and it is feared that OSPa
vaccination may trigger this process, even in the absence of bacterial
infection. OSPa vaccination in animals has triggered severe destructive
lyme arthritis. Studies of other tissue types relative to this concern
have not been performed. Dr. Steere, principal investigator for the
vaccine has expressed "concern" over this general issue.
Additional booster shots may exacerbate the problem. The vaccine was
approved without even a warning concerning this issue, and without
instructions to screen candidates for tissue type and not vaccinate
people with affected tissue types. Other tissue types may be at similar,
or lesser risk--this is unknown. A number of lawsuits were filed against
both Smith Kline and Connaught during the trials claiming adverse
events. However, the study reports no such adverse events. What happened
to those people? Anecdotal reports have been received about such events,
and some are reported in the Lyme Alliance News Letter. Other
information may be found on the Lymenet web site. If such incidents
occur, report them there, and, even more important, make sure they are
reported the the FDA Vaccine Adverse Events Reporting System (VAERS).
C. PEOPLE WITH OTHER HEALTH
CONDITIONS MAY BE AT RISK
People with health conditions
including arthrtitic condtions, muscoloskeletal disorders, certain
cardiac problems, neurologic problems, immunodeficiencies, a history of
alcohol or drug abuse, and those receiving long term antibiotic
treatment for any illness, along with those with hypersensitivity
reactions to previous vaccinations were excluded from the study. So were
those who had received treatment for lyme disease within three months of
the study. Pregnant mothers were also excluded. Thus, the safety and
efficacy of the vaccine in these groups has never been studied, and the
vaccine cannot be said to be safe for them.
D. VACCINE NOT APPROVED FOR
CHILDREN <15 YEARS: Children were not included in the original
study and the vaccine has not been approved for use in children. Trials
involving children are under way now. I would not permit a child of mine
to participate.
E. VACCINE NOT EFFECTIVE IN PEOPLE
> 70 YEARS OF AGE
Older people were included in the
study but the vaccine proved to be less effective in them than 15-69
years old so the vaccine was not approved for use in this age group. It
is uncertain why this variant result occurred.
F. SHORT TERM FOLLOW UP/LIMITED
STUDY
Another serious issue involving study
design is the short term follow-up of the study. Vaccinees were only
followed during the study and then for less than a year afterwards.
Thus, any mid to long term consequences of the vaccine, problems that
might not be detected within the time frame of the study, could not have
been recognized. Furthermore, while 11000 people were involved in the
study, only half received the vaccine. It is very possible that adverse
effects from the vaccine in the broader population might not have been
detected. Remember that a serious adverse event that occurs to 1 in 1000
people sounds insignificant. However that figure translates into 1000
people in 1,000,000. Now it sounds more significant. One final note, the
lack of long term follow up is of great concern in a disease that may
become latent and then reemerge later as lyme is known to do.
III. OTHER ISSUES/CONCERNS:
A. VACCINE DOESN'T PROTECT AGAINST
ALLCASES OR OTHER TICKBORNE DISORDERS/DON'T ABANDON OTHER PROTECTIVE
MEASURES OR GET A FALSE SENSE OF SECURITY
Since the vaccine does not protect
against all strains of the vaccine, or 100% of recipients, and since
protective levels are lower following shots 1 and 2, nor does the
vaccine protect against Babesiosis, Ehrlichiosis, Rocky Mountain Spotted
Fever, Tick Born Encephalitis, or a variety of other less common
tickborne diorders spread by the bite of the same tick, it is vital that
people in endemic areas not lower their vigilance with regard to other
protective measures (i.e., property management, proper attire, personal
repellents, and tick checks). A false sense of security could lead to
serious consequences. These facts should be carefully explained to all
vaccine recipients.
B. VACCINATION WILL CONFUSE ALREADY
PROBLEMATIC TESTS MAKING DIAGNOSIS EVEN MORE DIFFICULT:
Because the vaccine itself will cause certan antibodies to be produced,
the appearance of these antibodies will confuse existing testing geared
to those antibodies--the tests will not be able to distinguish between
antibodies caused by vaccination as opposed to those caused by
infection. Rather than question people tested for lyme as to whether
they have recieved the vaccine, the tests have been reconfigured to
discount certain significant and unique antibody responses. Thus,
already reliable testing has been rendered even less reliable--and this
affects both those who recieve the vaccine, and those who don't.
Diagnosis will be even more difficult, and people put at greater risk
for a delay that worsens the prognosis for treatment. Prompt diagnosis
and early treatment for proper duration, at proper dosage is essential
in preventing sequelae of the disease. This will be more difficult now
than it has been. Further, as mentioned above, a large number of
patients in the vaccine trials developed illnesses that could not be
confirmed as lyme. Perhaps this means that the vaccine alters the
natural presentation of the disease, and perhaps the natural course of
infection. We simply do not know without extensive additional study.
C. FDA/MEDICAL COMMUNITY HAS
RESERVATIONS ABOUT LYMERix:
The vaccine was approved with a record number of reservations by the FDA
and the approval came in record time, and in an atmosphere of pressure
on the FDA to generally speed up their drug approval process. This
atmosphere has been created by disease advocacy groups exerting
political pressure, in particular , HIV/AIDS patients. Unfortunately,
while HIV/AIDS patients have received new drugs in record time, the
pressure has been applied across the board and numerous drugs have been
approved but then pulled from the market recently due to safety issues.
IV. THE BOTTOM LINE:
Given all of the above it is apparent that the approval of the vaccine
was premature. Dr. Steere, principal investigator for the vaccine, has
expressed concern over its long and short term safety. The FDA approval
came with a unique number of reservations and concerns. Other
researchers have simply stated that this vaccine is not safe for human
beings. Vaccines given to dogs have turned out to have previously
undetected long term consequences, and have never been particularly
effective. Dr. Steere himself has declined to receive his own vaccine.
The vaccine is expensive ($60-80 per dose, with three doses needed in
the first year or earlier, and boosters needed but no one knows when, or
how often).
Study design glossed over the biggest
safety issues with the vaccine. Anecdotal reports of adverse events are
flowing in, but have been denied by Smith Kline, as they were during the
trials, despite the fact that several ended up in litigation. All of the
above data is based upon Smith Kline's own studies--there may be reason
to doubt the accuracy of this data, especially because the integrity of
many of the researchers has been questioned, and their aptitude for
diagnosing lyme disease is a matter of some debate amongst patients and
clinicians. There are at least two schools of thought when it comes to
lyme disease issues; it is fair to say that the researchers involved
represented only one school of those schools.
If there were a safe and effective
vaccine, lyme advocates would be wholeheartedly endorsing this as an
additional tool to add to the arsenal of protective measures available
to guard against, or minimize the risk of contracting a potentially
devastating illness. These advocates have no vested interest in
preventing a good vaccine from getting to market. Smith Kline does have
a vested interest in marketing the vaccine in which they have invested
millions of dollars.
The dubious benefits conferred by
vaccination with LYMErix are far outweighed by the known safety issues,
and the many unanswered questions.
Table 1.
Case Definitions for Lyme Disease
Definite Lyme
Disease
Any of the following clinical manifestations observed by the
investigator and at least one confirmatory laboratory test. In
subjects with erythema migrans, a photograph of the lesion was
also required.
Clinical
manifestations
Erythema migrans (an expanding red skin lesion, often with
partial central clearing)
Neurologic manifestations (meningitis, cranial neuritis)
Musculoskeletal manifestations (with objective evidence of
joint swelling in one or a few joints)
Cardiovascular manifestations (atrioventricular block)
Laboratory confirmation
Positive culture for B.burgdorferi from skin-biopsy
sample
Positive PCR result for B.burgdorferi DNA from
skin-biopsy sample, cerobrospinal fluid or joint fluid.
Seroconversion on Western blotting (defined as a negative
result followed by a positive result)
Positive IgM blot--at least 2
of the following 3 IgM bands: 23kd (outer-surface protein
C), 39kd, and 41 kd.
Positive IgG blot--at least 5 of the following 10 IgG bands:
18, 23, 28, 30, 39, 41, 45, 58, 66, and 93 kd
Laboratory-confirmed
asymptomatic B. burgdorferi infection
No symptoms
IgG seroconversion on Western blotting between month 2 and
month 12 in the first year or between month 12 and month 20 in
the second year
Possible Lyme disease
Influenza-like illness--fever,
fatigue, headache, chills, muscle aches, mild stiff neck or
backache without cough, coryza, diarrhea or vomiting-- with
IgM or IgG seroconverion on Western blotting
Physician-diagnosed erythema migrans lesions >5cm without
laboratory confirmation
Unconfirmed Lyme disease
All suspected cases that could
not be confirmed
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Table 2.
Attack Rates of Lyme Disease and Vaccine Efficacy in the Study
Population*
Lyme
Disease |
Year 1 |
Year 2 |
VACCINE (N=5469) |
PLACEBO
(N=5467) |
P VALUE |
VACCINE EFFICACY (95%CI) |
VACCINE (N=5469) |
PLACEBO (N=5467) |
P VALUE |
VACCINE EFFICACY (95%CI) |
No. of cases |
Attack Rate |
No. of cases |
Attack Rate |
|
|
No. of Cases |
Attack Rate |
No. of Cases |
Attack Rate |
|
|
|
% |
|
% |
|
% |
|
% |
|
% |
|
% |
Definite |
Erythema Migrans |
21 |
0.38 |
41 |
0.75 |
0.01 |
49 (14 to 70) |
15 |
0.27 |
65 |
1.19 |
<0.001 |
77(60 to 87) |
Neurologic Involvement |
0 |
0 |
1 |
0.02 |
|
|
0 |
0 |
1 |
0.02 |
|
|
Arthritis |
1 |
0.02 |
1 |
0.02 |
|
|
1 |
0.02 |
0 |
0 |
|
|
Carditis |
0 |
0 |
0 |
0 |
|
|
0 |
0 |
0 |
0 |
|
|
TOTAL Definite Cases |
22 |
0.40 |
43 |
0.79 |
0.009 |
49 (15 to 69) |
16 |
0.29 |
66 |
1.21 |
<0.001 |
68 (53 to 78) |
Asymptomatic |
Asymptomatic Infection |
2 |
0.04 |
13 |
0.24 |
0.004 |
83(32 to 97) |
0 |
0 |
15 |
0.27 |
0.001 |
100 (26 to 100) |
TOTAL Definite and Asymptomatic
cases |
24 |
0.44 |
56 |
1.02 |
<0.001 |
57 (31 to 73) |
16 |
0.29 |
81 |
1.48 |
<0.001 |
80 (66 to 88) |
Possible |
Influenza-like illness with
seroconversion |
13 |
0.24 |
17 |
0.31 |
0.46 |
24 (-57 to 63) |
12 |
0.22 |
21 |
0.88 |
<0.12 |
43 (-16 to 72) |
Physician-diagnosed erythema
migrans |
7 |
0.13 |
9 |
0.16 |
0.61 |
22 (-109 to 71) |
7 |
0.13 |
6 |
0.11 |
0.78 |
-17 (-247 to 61) |
TOTAL definite, asymptomatic,
and possible cases |
44 |
0.80 |
82 |
1.50 |
0.001 |
46 (23 to 63) |
35 |
0.64 |
108 |
1.98 |
<0.001 |
68 (53 to 78) |
Unconfirmed |
515 |
9.42 |
468 |
8.56 |
0.12 |
|
339 |
6.20 |
326 |
5.96 |
0.61 |
|
*CI
denotes 95% confidence interval
Tables 1 & 2 are taken from Steere,
et al. Vaccination against Lyme Disease with Recombinant Borrelia
burgdorferi Outer-Surface Lipoprotein A with Adjuvant [Original
Articles] N Engl J Med 1998 Jul 23;339(4):209-215 These tables are
modified for the web. Errors are my own.
PRESENTATION FRIDAY APRIL 9, 1999
12TH ANNUAL LYME DISEASE FOUNDATION SCIENTIFIC CONFERENCE
Ronald Schell PH.D.
University of Wisconsin School Of Medicine
Wisconsin State Laboratory of Hygiene
465 Henry Mall
Madison WI 53706
OspA Induces Lyme Arthritis In
Hamsters
Cindy L. Croke, Erik L. Munson, Steven D. Lovrich, John A. Christoperson,
Monica Remington, Steven M. Callister, and Ronald F. Schell. Wisconsin
State Laboratory of Hygiene and Departments of Medical Microbiology and
Immunology and Bacteriology, University of Wisconsin, Madison and
Microbiology Research Laboratory, Gunderson Medical Foundation, La
Crosse, Wisconsin
Recently we presented evidence that
adverse effects, particularly severe destructive Lyme Arthritis (SLDA)
can develop in vaccinated hamsters after challenge with Borellia
Burgdorferi sensu lato isolates. Hamsters were vaccinatee with
whole-cell preparations of inactivated B. Burgdorferi sensu stricto
isolates in alum. SDLA was readily evoked in vaccinated hamsters after
challenge with homologens or other B. Burgdorferi isolates. Arthritis
was evoked before high levels of protective borreliacidal antibody
developed or after the levels of protective antibody declined. We now
show that vaccination with recombinant OspA, the vaccine against Lyme
disease, can also induce SDLA. Hamsters were vaccinated withe 30, 60, or
120 mg or recombinant Osp A or an Osp A vaccine for dogs. Eleven days
after vaccination with the recombinant Osp A, vaccinated hamsters were
challenged in the hind paws with 10 (to the 6th power) B. Burgdorferi
isolates 297 or C-1-11. Swelling was detected 7 days after infection,
peaked on day 11 and gradually decreased. In addition, histologic
evidence or erosive and destructive arthritis was demonstrated in the
hind paws of Osp A vaccinated hamsters challenged with B. Burgodrferi.
These findings demonstrate that vaccination with Osp A can induce
adverse effects. Vaccination of humans with OspA should not be
reccomended until the vaccine has been shown to be incapable of inducing
SDLA.
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