Ann Allergy Asthma Immunol 118 (2017) 649e654

Contents lists available at ScienceDirect

How Allergen Extracts Are MadedFrom Source Materials to Allergen Extracts

Hymenoptera venoms used to produce allergen extracts
Greg Plunkett, PhD *; Robert S. Jacobson, MS y; David B.K. Golden, MD z
* ALK-Abello
y
z

Inc, Round Rock, Texas
Greer Laboratories, Lenoir, North Carolina
Johns Hopkins University, Baltimore, Maryland

A R T I C L E

I N F O

Article history:
Received for publication April 2, 2016.
Received in revised form May 20, 2016.
Accepted for publication May 31, 2016.

A B S T R A C T

Objective: To review the methods and materials used for collection, purification, commercial production,
and clinical application of Hymenoptera venoms.
Data Sources: Most of the sources for this review are the experience and expertise of the authors. Published
reports and review articles on Hymenoptera venom collection and production were identified through
database searches (PubMed).
Study Selections: Studies describing the methods for Hymenoptera venom collection and production were
selected for review.
Results: Meticulous methods for identification and collection of the insects are required. Collection and
purification of the venoms from the insects are based on validated methods and result in a commercial
extract that is standardized for the major allergenic proteins required for accurate diagnosis and safe and
effective treatment of patients allergic to insect sting. The steps required for mixing, purifying, testing, and
standardizing the products are described.
Conclusion: Hymenoptera venom extracts were developed using many new methods for the collection,
purification, and commercial production of the unique materials required for this product. Clinical applications for diagnosis and treatment are affected by the integrity and stability of the allergens after
processing and purification.
! 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Important Hymenoptera Insects
Bees, Wasps, Yellow Jackets, and Hornets
The flying insects of the order Hymenoptera (bees and wasps)
that are responsible for anaphylaxis attributable to venom hypersensitivity are largely similar between the United States and
Europe. Honeybees (Apis mellifera), native to Europe, were introduced into the United States nearly 400 years ago, becoming
established throughout the country, and are valued on both continents for pollinating crops, honey, and wax.1 Stinging risk occurs
throughout the year from their perennial colonies but minimally
during colder months. Some strains are more defensive than others.
The introduced Africanized or “killer” bees, which migrated from
Brazil and were intentionally brought from Africa, have reached the
Southern and Southwestern United States, where their extremely
Reprints: David B.K. Golden, MD, Johns Hopkins University, 7939 Honeygo Blvd,
Room 219, Baltimore, MD 21236; E-mail: dgolden1@jhmi.edu.
Disclosures: Dr Golden reported receiving honoraria and serving on the speaker’s
bureau for Genentech and Greer Laboratories, working as a consultant for Greer
Laboratories, and receiving a research grant and working on a clinical trial for
Genentech.

defensive behavior poses a serious risk. Honeybees are unique
among important stinging species because their barbed stings
readily detach and remain in the skin, although yellow jackets are
sometimes unable to remove their stings.2
The genera Vespa, Dolichovespula, and Vespula (hornets and
yellow jackets, with Vespula often simply called wasps or true
wasps in Europe) are important in Europe and the United States,
although a member of the first genusdVespa crabro or European
hornetdwas introduced into the United States around 1840.
Although V crabro is widespread in Europe, 2 other hornets (one
native, another introduced) have limited distributions. All 3 genera
make paper nests composed of several combs usually covered by an
envelope, with colonies typically lasting only one season, and will
defend their nests aggressively if disturbed.
Vespula and Dolichovespula are native and widespread in the
United States and Europe, with the former genus building large
colonies, often in the ground or in structures, and the latter usually
building exposed nests on tree branches or under eaves. Several
species of yellow jackets are scavengers with large colonies; a
prime example is Vespula germanica, native to Europe (which
usually includes Paravespula) and established in much of the United
States. Scavenging species are attracted to human food, making

http://dx.doi.org/10.1016/j.anai.2016.05.027
1081-1206/! 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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G. Plunkett et al. / Ann Allergy Asthma Immunol 118 (2017) 649e654

unintentional contact or ingestion of the insect a risk. European
species cross-react well with most American species but less so
with the American Vespula squamosa.3
Dolichovespula includes several species whose American members, particularly the large and widespread baldfaced species
(Dolichovespula maculata) with its large gray nests, are sometimes
called hornets. The closely related aerial yellow jacket or yellow
hornet (Dolichovespula arenaria) is a smaller member of this genus.
They both have sibling species in Europe (where they are sometimes called tree wasps) with which they can be expected to crossreact.4
Paper wasps (Polistes species) are rather slender insects that
build single exposed combs (ie, no covering envelope). They are
found through most of the contiguous United States and much of
Europe, particularly warmer regions. Mass stinging is unlikely
because of their small colonies. American and European species are
partially cross-reactive, although one of the European species
(Polistes dominula) has become established in the United States.5,6
Fire Ants and Other Ants
Five species of fire ants (Solenopsis)d3 native and 2 importeddare in the United States; no species are found in Europe. Two
imported species (Solenopsis richteri, the black species, and especially Solenopsis invicta, the red species) are introductions from
South America that present important stinging hazards throughout
much of the southeastern United States and occasionally westward,
particularly when their soil mounds are disturbed.7 Additional
medically important ants in the United States include harvester
ants (Pogonomyrmex) distributed mostly in the Western United
States, with one species reaching the Southeast and Asian needle
ants (Brachyponera chinensis) currently restricted to the Southeast.
Extracts are available only for imported fire ants; their venoms are
not cross-reactive with the other genera.8,9
Collection of Stinging Insects
Obtaining stinging insects for venom production presents
several challenges. A collector must obtain sufficient leads from
property owners or managers who can report active colonies, and
such reports must be screened to avoid wasting time with
unwanted species of insects (eg, honeybees) and to be sure the nest
is accessible or at least the insects can be trapped. Before collecting,
the collector must be certain no pesticides or chemicals have been
or are used (although carbon dioxide is permitted). Insects must be
kept alive until frozen for storage. Beekeepers and pest control
operators often receive gratuitous calls, whereas others must
advertise free insect removal.
There are many ways of collecting, and collectors have their own
trade secrets. Techniques range from collecting entire nests (which
are frozen intact and dissected later while maintained frozen),
trapping insects, and using a special vacuum cleaner designed to
prevent killing and desiccating the insects; in the last 2 cases,
prompt freezing is critical. Species are kept segregated, so the
collector must bag the insects from each nest separately. A chesttype freezer is used for storage to avoid loss of cold when opened.
Because only female insects sting, collectors often time their
collecting for maximum female populations. Normally, this is late
summer or autumn for vespines, but this may be past the peak for
Polistes.
Collected insects must remain frozen until just before dissection. On receipt at the manufacturer, insects are examined. This
entails verification that the insects are still frozen (usually by the
presence of dry ice in the shipping container), confirmation of the
species, certification that no pesticides or other chemicals were
used, confirmation there are no odors atypical of the species (ie,
attributable to chemicals or spoilage), random sampling to assess

female percentage, and subtraction of weight due to debris and
water ice. Finally, female insects are randomly sampled, thawed,
and dissected to ensure the venom sacs are light yellow or whitish
in color (depending on the species) as evidence that insects were
frozen alive. The usable weight of female insects is calculated for
both payment and raw material inventory purposes. If criteria are
not met, insects are rejected.
Honeybee venom (HBV) is collected by electrical stimulation, as
discussed below. Because fire ant extracts are whole body, their
colonies are scooped into containers, and then water is used to float
the ants from the soil, which is a natural behavior for fire ants. The
floating ants are scooped and stored frozen.
Venom Processing
Hymenoptera Venom Sources: History
Testing and treatment for allergy to flying insect stings began
nearly 100 years ago when in 1925 Braun10 treated a HBV allergic
patient with an extract from bee posterior bodies. From 1930 to
1954, studies reported that treatment with HBV and whole-body
extracts was equally effective.11 In the 1960s, Benton and
colleagues12 from Penn State University designed an improved
apparatus for collecting pure HBV using electrostimulation.12
Collection of vespid venom was described by Loveless and Fackler13 in 1956. As these purified venom sources improved and
venom became more readily available, clinical trials during the
1970s and 1980s established that whole-body extracts were not
effective for testing or treatment.14e16 Venoms were found to be
better than whole-body extracts, resulting in commercial venom
products becoming available from Hollister-Stier (now Jubilant
Hollister Stier) and Pharmacia Labs (now ALK-Abello Inc) in 1979
to 1980 (Table 1).17e19
Table 1
History of Venom Extracts Used for Immunotherapy
Year

Event

1925

Braun successfully tested and treated honeybee allergic patient with
extract made from posterior 1/800 of HB bodies (WBE)
Benson and Semenov reported on a honeybee allergic beekeeper
who had positive skin test results to HBV, HB sting apparatuses,
and HB bodies w/o sting apparatuses
Markovic and Molnar described electrical stimulation for the
collection of honeybee
Loveless and Fackler reported on successful diagnostic and
therapeutic use of venom sac extracts
Benton and colleagues reported an improved method for electrical
collection of honeybee venom
Bermon and Brown reported positive whole-body extract skin test
results in 37% of inmates without positive histories (n ¼ 200) and
in 40% of inmates who had never been stung (n ¼ 15)
Schwartz reported no significant difference between skin test
reactivity to whole-body extract in sting allergic patients and
control patients
Torsney reported 8 insect sting allergy fatalities in patients treated
with whole-body extract
Small samples of Hymenoptera venoms to Johns Hopkins University
Ramp up of venom source materials from Penn State University (Dr
Benton, honeybee venom) and Rockefeller University (Dr King,
vespids)
Sobotka et al reported that Hymenoptera venoms induced histamine
release in basophil leukocytes from insect allergic patients
Hopkins asked to treat a beekeeper’s 4-year-old son, whole-body
extract failure, whose sister had previously died of a honeybee
sting
Hunt et al reported on the diagnostic specificity of venom skin tests
in 30 patients
Favorable results from the Johns Hopkins clinical trials
Hunt reported blinded placebo-controlled trial with 60 patients
US Food and Drug Administration grants licenses to Hollister-Stier,
Pharmacia Labs (ALK purchased in 1987)

1930

1954
1956
1963
1965

1965

1973
1973
1970s

1974
1974

1976
1976
1978
1979e1980

 G. Plunkett et al. / Ann Allergy Asthma Immunol 118 (2017) 649e654

How Are Hymenoptera Venoms Obtained?
Honeybee venom
The method for collection of HBV using electrostimulation was
perfected by Benton and colleaques12 from Penn State University,
and Dr Benton, along with Miles Guralnick, formed Vespa Labs in
Spring Mills, PA, to supply insect venoms for immunotherapy.
Electrostimulation involves exposing a bee to a small electric current from a wire grid connected to a carlike battery, causing the bee
to automatically sting through a plastic wrap, leaving a small bead
of venom (Fig 1). The battery and grid apparatus is placed near a
commercial hive. As the bees explore the device and land on the
grid, the stinging impulse also releases attack pheromones and
soon is covered in hundreds of bees. The plastic wrap covering the
grid does not impede the barbed stinger because it retracts, so the
bees are not harmed. Each sting through the plastic deposits
approximately 50 mL of pure venom so after a short time several
grams of pure venom can be collected. The purified HBV source
material is dried on the plastic wrap then scraped off. More
recently, the plastic wrap has been replaced by a latex-free membrane that is safer for the bees.
Vespid and wasp venom
In 1956, Loveless and Fackler13 reported the successful use of
venom sac extracts for immunotherapy. Because electrostimulation
of hives was not practical for these insects, venom sac isolation was
the preferred path for collecting venom. The scientists at Vespa
Labs along with scientists at Hollister-Stier Labs, Spokane, WA,
developed for commercial purposes the technique described by
King et al,20 who described removing venom sacs and characterizing the components in the venoms (Fig 2). The venoms collected
by these methods in the middle 1970s were used for immunotherapy clinical trials at Johns Hopkins University and Mayo Clinic
that were the basis of US Food and Drug Administration (FDA)
approval of the commercial venom products.17,21,22
Today there is an extensive network of private collectors and
beekeepers that supplies the purified HBV and insects for further
processing at Vespa Labs and Jubilant Hollister Stier. This network is
still the sole supplier of venom source material used for FDAapproved immunotherapy. Vespa Labs is now part of the global
allergy extract company ALK (Hørsholm, Denmark), and ALK Inc
(Round Rock, Texas) distributes Hymenoptera venom products in
the United States. The vespid and paper wasp insect collectors are
responsible for finding nests for at least 6 species of yellow jacket
and 4 to 5 species of Polistes wasps. The insects are rendered
harmless using carbon dioxide and then delivered to the sacpulling teams frozen.

Figure 1. Collection of honey bee venom by electrostimulation. Reproduced with
permission of Vespa Labs (ALK-Abello Inc).

651

Imported fire ant source material
Venom from Solenopsis richteri and invicta fire ants is not
available for immunotherapy. Manufacturers supply weight/volume whole-body extracts that are nonstandardized (no standard of
potency). Insects are collected from nests and then freeze-dried
before extraction. Analysis of these extracts has revealed sufficient venom proteins for use in immunotherapy diagnosis and
treatment.23e25 Batch to batch variability and stability are not
known for fire ant extracts in the United States.
Manufacture of Insect Extracts
FDA approval of venom products
The FDA approved stinging insect venom products in 1979 to
1980, subsequently removing the corresponding whole-body
extracts from the market. Six venom product types are approved
in the United States. Honeybee, domestic (Apis mellifera), yellow
jacket (Vespula species), yellow hornet (Dolichovespula arenaria),
white-faced hornet (Dolichovespula maculata), paper wasps
(Polistes species), and a mixture of yellow jacket, yellow hornet, and
white-faced hornet (mixed vespids). There are various configurations, of single use or multidose vials, and they are formulated to be
100 mg/mL when reconstituted (300 mg/mL for mixed vespids). In
Europe, there are some alternate venom product types, such as
dialyzed venom to remove low-molecular-weight nonallergenic
material and vaccines of venom adsorbed to alum. Below is a discussion of US manufactured products only.
Manufacturing Steps
Species mixtures
Yellow jacket and paper wasp are formulated with a mixture of
species within the genus and include the most common species
that cause allergic reactions. Yellow jacket venom contains Vespula
species of Vespula vulgaris, V germanica, Vespula maculifrons, Vespula
pensylvanica, Vespula flavopilosa, and Vespula squamosa. The ALK
venom package inserts specify that these species are present in
their yellow jacket venom extract. These are the most commonly
used species in the Jubilant Hollister Stier venoms, although their
package insert allows for other Vespula species. From the ALK
package insert, the Polistes paper wasp products are mixtures of
Polistes annularis, Polistes apachus, Polistes exclamans, Polistes fuscatus, and Polistes metricus. Jubilant Hollister Stier paper wasp
products have contained mixtures of P metricus, P exclamans, and
P fuscatus, recently removing P annularis. There is extensive (but not
absolute) cross-reactivity among the venoms of the Vespula genus
and also among those of the Polistes genus. The species chosen for
the commercial mixtures are the ones that most commonly sting
people. Venom of V squamosa was added to the yellow jacket
mixture early (1980) because it possesses some unique allergenic
activity and is less cross-reactive with other Vespula species.
European venom extracts can also contain mixtures of Vespula
and Polistes species. Some contain the same mixtures as used in the
United States, whereas others have fewer species, such as V
germanica and V vulgaris. There has also been the addition in some
markets of P dominula, also called the Mediterranean paper wasp,
as a single species extract. This species, even though its presence is
increasing in the United States, has not been introduced in FDAapproved venoms.
Preparation of intermediate venom products
HBV intermediate product is pure dried venom collected from
electrostimulation. The vespid and wasp venoms are extracts of
venom sacs that are individually pulled from insects collected and
frozen alive. Each sac is pulled from the insect and placed in an
extraction fluid containing a small amount of an acetic acid/
b-alanine buffer. Hundreds of sacs are extracted, and the mixture is

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G. Plunkett et al. / Ann Allergy Asthma Immunol 118 (2017) 649e654

Figure 2. Collection of Vespula and Polistes venom. Reproduced with permission of Vespa Labs (ALK-Abello Inc).

blended, filtered, and freeze-dried into bulk vials. Yellow jacket
species and wasp species are mixed into the final bulk vials. All the
venom bulk vials are stable for at least 30 months according to one
manufacturer.
Intermediate testing
Initial estimates of venom potency are made by measuring the
total protein content (even though this is not a direct measure of
allergenic potency). The bulk intermediate vials are tested for total
protein by the FDA-approved Lowry method (Laboratory of
Immunobiology of the FDA, Methods of the Allergenics Products
Testing Laboratory, Docket No. 94N0012 October 1993). During the
development of commercial products in the late 1970s, 2 enzymes
were discovered to be major allergen proteins, phospholipase and
hyaluronidase. Enzyme activity identified the presence of these 2
proteins and therefore became part of the potency testing. Even
though the proteins are not cross-reactive between honeybees and
vespids, the same enzyme assays were performed for all venom
bulk vials. Each batch of venom bulk vials has minimum enzyme
level requirements.
Final commercial venom products
The final venom products are reconstituted to 100 mg/mL based
on the Lowry total protein content of the bulk vials. For mixed
vespid venom, yellow jacket, yellow hornet, and white-faced hornet intermediate vials are combined and formulated to 300 mg/mL.
The reconstitution solution contains mannitol as a freeze-drying
agent and helps stabilize the venom protein. ALK adds human
serum albumin along with the mannitol as an additional freezedrying stabilizing agent and is the primary difference in the
venom products in the United States. The vials are commercially
available as freeze-dried single or multidose vials at 100 mg/mL
(300 mg/mL for mixed vespid venom) when reconstituted.
Standardization
Venom source material is analyzed for the allergen enzyme
activity, and native polyacrylamide electrophoresis is performed.
Each venom has a unique pattern. One of the major allergens in
vespid venom is antigen 5 or vespid 5. The enzyme activity is not
known, and no immunoassay was developed, so this important
allergen is not measured in US extracts. It is a prominent protein
band in electrophoresis. Final commercial vials are tested for total
protein, phospholipase, and hyaluronidase and must meet certain
limits as specified in the manufacturers’ FDA licenses. IgE binding is
not determined for FDA-licensed products; however, potency by
IgE binding is determined in European venoms in addition to the
enzyme assays. Sterility and safety testing is also performed before
release for sale. Expiration dating of the freeze-dried powder is
determined by stability studies performed by each manufacturer.
Expiration studies of the reconstituted vials using human serum

albumin with phenol diluent have also been performed with recommendations stated in the package insert.
Composition of venoms
Since the introduction of venom products for immunotherapy in
the late 1970s, much as been learned about their makeup. Lowmolecular-weight components are present, many of which are
active pharmacologic agents composed of vasoactive amines and
peptides. These components are not removed from the venom
products and most likely are responsible for limiting intradermal
skin test diagnosis to concentration not exceeding 1 mg/mL. Many
additional allergen proteins have been described in addition to the
phospholipase and hyaluronidase enzyme allergens. In the vespids,
group 5, such as Ves v 5, has been found to be an important
allergen, but the enzymatic function is not known. Purified Ves v 5
was used as an electrophoresis marker to demonstrate the presence
of this protein in US venom products.
Implications for Clinical Practice
Hymenoptera insect extracts are necessary for accurate diagnosis and preventive treatment of insect sting allergy. The process
from source materials to allergenic extracts has considerable effect
on the clinical applications.
The selection and collection of insect species are critical to all
subsequent characterization of the commercial product for diagnosis and treatment. The purity and allergenic activity of the
collected materials must be optimal and consistent. There are
numerous species of Vespula and Polistes, which vary in different
regions of the United States. For any nonentomologist, the accurate
identification of these species is difficult and unreliable.26 A trained
and skilled network of collectors and vigilance in review of the
materials that arrive at the laboratory are required to ensure the
allergenic specificity, activity, and purity of the products. There are
only 2 allergen laboratories in the United States that supply Hymenoptera extracts for clinical use, and their products have been
described above. The clinician must always be aware that there are
species that are not represented in the commercial products and
may be antigenically distinct from the more common species. This
could lead to negative diagnostic test results in a patient who is
allergic to a specific species of vespid.27 If an extract varies in the
type or quantity of certain species, then the ability to detect the
allergy on testing or to protect with venom immunotherapy could
be reduced.
The preparation of the extract from the raw materials is critical
in determining the reliability of testing and treatment. At each of
the steps described above for intermediate products and standardization, any change or deficiency could greatly affect the clinical outcome. At risk is the integrity and stability of each allergenic
protein in each of the venoms being prepared. Loss of activity could

 G. Plunkett et al. / Ann Allergy Asthma Immunol 118 (2017) 649e654

result from susceptibility to reagents used in the processing, mechanical degradation, enzymatic degradation, molecular instability,
and binding characteristics. For example, the activity of the major
vespid allergen Ves v 5 is not optimal for diagnosis, and the
detection of yellow jacket allergy can be improved by spiking the
extract with this protein.28
The procedures for standardization can also have an effect on
clinical practice. As described above, the Hymenoptera venoms are
standardized by the FDA based on measurement of phospholipase
(HBV) or hyaluronidase (vespid venoms), although there are specifications for both enzymes in all Hymenoptera venom extracts.
Without quantification of the major vespid allergen, Ves v 5, it is
difficult to be certain of the equivalence of products from different
batches or different laboratories. Notably, despite numerous occasions that required changing a patient’s treatment to a different
product, there has been no report of any adverse outcomes.
Diagnostic applications of Hymenoptera extracts are for in vivo
and in vitro testing methods. Skin tests use the commercial extract
at concentrations found to provide optimal sensitivity and specificity (up to 1.0 mg/mL for intradermal testing). Higher concentrations give improved sensitivity but can also cause false-positive
results because of local irritative effects.29 Greater diagnostic
accuracy is achieved with a concentration of 10 mg/mL if the venom
is dialyzed to reduce these irritative effects.30 Dialyzed venoms are
not commercially available in the United States but are common in
Europe.31 Commercial reagents for skin prick testing are not
available because skin prick testing with venoms is much less
sensitive than intradermal testing and is often omitted in favor of
intradermal tests starting with very low concentrations (0.001
mg/mL). When skin prick tests are performed as a preliminary test,
the concentrations used range from 1 to 100 mg/mL.32,33 Diagnostic
testing for fire ant allergy uses the commercial whole-body
extracts. Although venoms might be superior, they are not
commercially available. Laboratory methods that use Hymenoptera
extracts are primarily enzyme-linked immunoassays for allergen
specific IgE antibodies. In these assays, the accuracy may be
affected not only by the activity of the many allergens in each
venom but also by their binding characteristics for the solid phase
used in the assay.34 Nevertheless, neither skin tests nor in vitro
tests can detect all cases of insect sting allergy. Another in vitro
method that shows promise is the basophil activation test, which
uses the same venom extracts to elicit basophil activation (not
necessarily IgE dependent).35e37
One of the dilemmas of diagnostic specificity for Hymenoptera
venoms is the cross-reactivity between genera and species.
Radioallergosorbent assay inhibition tests have been used to
determine whether patients with dual yellow jacket and Polistes
wasp venom sensitivity can be treated with just 1 of the venoms.38
The use of recombinant venom allergens for in vitro measurement
of IgE can identify the primary allergy in patients with dual positive
test results for honeybee and yellow jacket venoms.39e41 However,
for reliable accuracy, these tests would have to include multiple
recombinant allergens for each venom.
Therapeutic application of Hymenoptera products prevents
severe allergic reactions to stings. Early clinical trials revealed the
safety and efficacy of venom immunotherapy.17 Clinical experience
in thousands (if not millions) of patients during the past 40 years
has confirmed that venom immunotherapy prevents systemic
reactions in 80% to 98% of affected patients.29 The safety of venom
immunotherapy has been comparable to other standard types of
allergen immunotherapy (eg, grass or cat). The choice of which
venoms to use for treatment can be facilitated with in vitro tests to
clarify the cross-reactivity of the venoms, as described above.
Immunotherapy for fire ant sting allergy is performed using wholebody extracts, which contain sufficient venom allergens to provide
significant clinical protection from anaphylaxis.23

653

Conclusions
The development of specific materials to be used for diagnosis and treatment of Hymenoptera venom allergy posed
unique challenges in the collection and processing of the allergens. Insects of known species must be obtained by knowledgeable collectors and must be handled from the outset in a
way that preserves the integrity and activity of the venom.
Identification of the relevant species requires expertise, and
locating and collecting them require understanding of their
nesting and foraging habits. In the case of honeybee, the method
of venom collection is unique and requires live insects. Fire ant
extracts are prepared from whole insect bodies without separation of the venom.
The crude venoms must be assessed qualitatively and quantitatively for purity and allergenic activity. The intermediate venom
product must be purified and stabilized to eliminate most small
molecules that can increase adverse effects and to avoid enzymatic
degradation of the allergens. The choice of specific species and their
relative quantities for the yellow jacket and Polistes products must
be consistent. Finally, venoms must be standardized by quantitation of specific allergenic proteins.
The use of commercial Hymenoptera venoms for diagnosis and
treatment of insect sting allergy is both improved and hampered
by the methods of production. Hymenoptera venoms were the
first allergenic extracts to be standardized by the FDA. On the
other hand, the vespid venoms are not routinely standardized for
the major allergen Ves v 5. Recent studies found that some allergens may be underrepresented in the commercial venoms, which
might reduce the diagnostic accuracy and therapeutic efficacy of
the venoms.28,42 In the future, the use of recombinant venom
allergens to supplement the commercial venoms might address
this problem (and some of those below as well). Another potential
improvement in the commercial venom products would be more
efficient purification (eg, dialysis) to reduce the irritative components that limit the concentration used for skin tests and
contribute to local reactions to immunotherapy.30,31 Purified
venoms are available in Europe but not in the United States.
Another possible improvement would be the availability of additional species, either individually or within a species mix (eg,
Vespula, Polistes). There are patients with specific sensitivity to
bumble bees, Mediterranean wasps (P dominula), or other unique
species of wasp or yellow jacket that are not currently represented
in the commercial products.27 It is believed that fire ant venom
would be superior to the whole-body extract for testing and
immunotherapy. It would useful if fire ant venom could be made
available in a commercial product.
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