Combinations of plasma immunoglobulins and antigen-specific immunoglobulins for modifying the immune system and treating or preventing allergic diseases

Abstract

The present invention relates to the use of a combination of plasma immunoglobulins such as intramuscular immunoglobulins and polyclonal antigen-specific immunoglobulins in the treatment or prevention of allergic diseases. The present invention also relates to a pharmaceutical composition comprising plasma immunoglobulins and polyclonal antigen-specific immunoglobulins.

Description

Technical Field

[0001] The present invention relates to the treatment of allergic diseases. In particular, the present invention relates to the use of a combination of pooled immunoglobulins and antigen-specific immunoglobulins in the treatment or prevention of allergic diseases. Background Art

[0002] Allergic diseases afflict a large portion of humans and pets. Allergen immunotherapy is sometimes used to build up an individual's tolerance to allergens. In treatment, allergen injections are given in two phases: a build-up phase and a maintenance phase. The build-up phase may involve injections of increasing amounts of allergen, approximately one to three times per week for three to six months. Once an effective dose is reached, the maintenance phase begins with additional injections, approximately every two to four weeks, for several years. Therefore, both the build-up phase and the maintenance phase are very onerous.

[0003] It is an object of the present invention to provide improved pharmaceutical compositions and methods for the treatment or prevention of allergic diseases.

[0004] This and other objects of the present invention will be better understood with reference to the following detailed description of the preferred embodiments. Note that the above-mentioned objects are statements of motivations for the present invention rather than commitments. All embodiments of the present invention described below or the invention defined in each of the claims may not necessarily satisfy all objects. Summary of the invention

[0005] According to one aspect of the present invention, a combination of plasma immunoglobulins and antigen-specific immunoglobulins can be used to treat or prevent allergic diseases.

[0006] In another aspect, the invention encompasses the use of a combination of plasma immunoglobulins and antigen-specific immunoglobulins for the treatment or prevention of allergic disease.

[0007] In another aspect, the present invention is a pharmaceutical composition for treating or preventing allergic diseases, comprising plasma immunoglobulin and antigen-specific immunoglobulin.

[0008] In another aspect, the plasma immunoglobulin is intramuscular immunoglobulin.

[0009] In another aspect, the intramuscular immunoglobulin is human intramuscular immunoglobulin.

[0010] In another aspect, the plasma immunoglobulin is human plasma immunoglobulin.

[0011] In another aspect, the plasma immunoglobulin is from a non-human species.

[0012] In another aspect, the plasma immunoglobulin and the antigen-specific immunoglobulin are from the same species.

[0013] In another aspect, the antigen-specific immunoglobulin is selected from the group consisting of a polyclonal anti-tetanus toxoid immunoglobulin, a polyclonal anti-Rh immunoglobulin, a polyclonal anti-hepatitis B immunoglobulin, a polyclonal anti-rabies immunoglobulin and a polyclonal anti-varicella immunoglobulin.

[0014] In another aspect, the plasma immunoglobulin is greater than 50 mg / kg body weight.

[0015] In another aspect, the present invention is a method for treating or preventing allergic diseases, comprising administering an injection of plasma immunoglobulin and antigen-specific immunoglobulin.

[0016] In another aspect, the present invention is a kit comprising an aliquot of plasma immunoglobulin, an aliquot of antigen-specific immunoglobulin, and instructions associated with the kit directing the use of the aliquot of plasma immunoglobulin and the aliquot of antigen-specific immunoglobulin to treat or prevent allergic disease.

[0017] In another aspect, the present invention is a kit comprising aliquots of a mixture of plasma immunoglobulins and antigen-specific immunoglobulins, and instructions associated with the kit directing the use of the aliquots of the mixture of plasma immunoglobulins and antigen-specific immunoglobulins for treating or preventing allergic diseases.

[0018] The foregoing may only cover some aspects of the present invention. Other aspects of the present invention may be understood by reference to the following description of at least one preferred mode for implementing the present invention according to one or more embodiments. The following modes for implementing the present invention are not definitions of the present invention itself, but are merely examples of inventive features of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] At least one mode of implementing the present invention will be described according to several embodiments with reference to the following drawings, in which:

[0020] Figure 1A is a graph showing attenuation of anti-OVA IgE response by combined injection of IMIG and polyclonal anti-tetanus toxoid Ig.

[0021] Figure 1B is a graph showing no change in anti-OVA IgG response by combined injection of IMIG and polyclonal anti-tetanus toxoid Ig.

[0022] Figure 1C is a graph showing OVA-induced IL-4 in OVA-immunized mice that received a combined injection of IMIG and polyclonal anti-tetanus toxoid Ig.

[0023] Figure 1Dis a graph showing OVA-induced IL-2 in OVA-immunized mice that received a combined injection of IMIG and polyclonal anti-tetanus toxoid Ig.

[0024] Figure 2A It is a graph showing OVA-induced IL-2 in spleen cells of OVA-immunized mice injected with IMIG and anti-varicella Ig.

[0025] Figure 2B It is a graph showing OVA-induced IL-4 in spleen cells of OVA-immunized mice injected with IMIG and anti-varicella Ig.

[0026] Figure 3A is a graph showing total serum IgG levels in dog blood before sensitization with peanut butter and treatment with dog IMIG and dog anti-rabies immune Ig or with human IMIG and human anti-tetanus Ig.

[0027] Figure 3B is a graph showing total serum IgG levels in dog blood after sensitization with peanut butter and treatment with dog IMIG and dog anti-rabies immune Ig or with human IMIG and human anti-tetanus Ig.

[0028] Figure 3C is a graph showing total serum IgE levels in dog blood before sensitization with peanut butter and treatment with dog IMIG and dog anti-rabies immune Ig or with human IMIG and human anti-tetanus Ig.

[0029] Figure 3D is a graph showing total serum IgE levels in dog blood after sensitization with peanut butter and treatment with dog IMIG and dog anti-rabies immune Ig or with human IMIG and human anti-tetanus Ig.

[0030] Figure 3E is a graph showing IL-2 production by peripheral blood lymphocytes of dogs stimulated with ConA before sensitization with peanut butter and treatment with dog IMIG and dog anti-rabies immune Ig or with human IMIG and human anti-tetanus Ig.

[0031] Figure 3F is a graph showing IL-2 production by ConA-stimulated peripheral blood lymphocytes of dogs after sensitization with peanut butter and treatment with dog IMIG and dog anti-rabies immune Ig or with human IMIG and human anti-tetanus Ig.

[0032] Figure 3G is a graph showing IL-4 production by ConA-stimulated dog peripheral blood lymphocytes before sensitization with peanut butter and treatment with dog IMIG and dog anti-rabies immune Ig or with human IMIG and human anti-tetanus Ig.

[0033] Figure 3His a graph showing IL-4 production by ConA-stimulated peripheral blood lymphocytes of dogs after sensitization with peanut butter and treatment with dog IMIG and dog anti-rabies immune Ig or with human IMIG and human anti-tetanus Ig.

[0034] Fig. 3I is a graph showing the ratio of IL-2 / IL-4 levels produced by peripheral blood lymphocytes of dogs stimulated with ConA before and after sensitization with peanut butter and treatment with dog IMIG and dog anti-rabies immune Ig or with human IMIG and human anti-tetanus Ig.

[0035] Figure 3J is a graph showing IL-2 and IL-4 production by peripheral blood lymphocytes of dogs stimulated with peanut butter Ag after sensitization with peanut butter and treatment with dog IMIG and dog anti-rabies immune Ig or with human IMIG and human anti-tetanus Ig.

[0036] Figure 3K is a graph showing the ratio of IL-2 / IL-4 levels produced by peripheral blood lymphocytes of dogs stimulated with peanut butter Ag after sensitization with peanut butter and treatment with dog IMIG and dog anti-rabies immune Ig or with human IMIG and human anti-tetanus Ig.

[0037] Figure 4A is a graph showing OVA-specific IgE serum levels in OVA-immunized mice after combined infusion of different doses of IMIG and anti-tetanus Ig.

[0038] Figure 4B is a graph showing OVA-specific IgG serum levels in OVA-immunized mice after combined infusion of different doses of IMIG and anti-tetanus Ig.

[0039] Figure 4C is a graph showing IL-4 production by OVA-stimulated splenocytes in OVA-immunized mice following combined infusion of different doses of IMIG and anti-tetanus Ig.

[0040] Figure 4D is a graph showing IL-2 production by OVA-stimulated splenocytes in OVA-immunized mice following combined infusion of different doses of IMIG and anti-tetanus Ig.

[0041] Figure 4E is a graph showing the ratio of IL-2 / IL-4 levels produced by OVA-stimulated splenocytes in OVA-immunized mice after combined infusion of different doses of IMIG and anti-tetanus Ig. DETAILED DESCRIPTION

[0042] At least one mode for implementing the present invention is described in detail according to the embodiments.

[0043] The pharmaceutical composition of the present invention is a combination of pooled plasma immunoglobulins and antigen-specific polyclonal immunoglobulins.

[0044] Plasma immunoglobulins are typically prepared from the sera of at least 1000 donors and have been used to treat patients with primary immunodeficiency diseases. Depending on how the plasma immunoglobulin is formulated and administered, it may be referred to as intramuscular immunoglobulin ("IMIG"), intravenous immunoglobulin ("IVIG"), subcutaneous immunoglobulin ("SCIG"), or intraperitoneal immunoglobulin ("IPIG").

[0045] Antigen-specific polyclonal immunoglobulins are prepared with high numbers of antibodies against a specific pathogen, such as varicella zoster virus, or against a specific antigen, such as tetanus toxoid.

[0046] The present inventors have discovered that a combination of pooled plasma immunoglobulins and antigen-specific polyclonal immunoglobulins can be used to treat or prevent allergic diseases.

[0047] As will be described in detail below, the inventors have conducted experiments using various antigen-specific immunoglobulins directed against various antigens. In view of the significant differences in preparation and chemical composition between the antigen-specific immunoglobulins used (polyclonal anti-tetanus immunoglobulin, polyclonal anti-rabies immunoglobulin and polyclonal anti-varicella immunoglobulin), the combination of plasma immunoglobulin with any antigen-specific immunoglobulin (including but not limited to polyclonal anti-Rh immunoglobulin and polyclonal anti-hepatitis B immunoglobulin) is expected to result in similar modifications of the immune system of the treated human or animal and similarly prevent and / or treat allergic diseases.

[0048] For the treatment and prevention of allergic diseases in humans and pets, the plasma immunoglobulin component of the combination may be a plasma immunoglobulin approved for use in humans, such as but not limited to Gamunex TM and Hizentra TM .

[0049] Plasma immunoglobulins and antigen-specific polyclonal immunoglobulins can be administered in any suitable manner. For example, the antibodies can be administered in a non-immunogenic amount in a non-immunogenic (i.e., adjuvant-free) form, such as intramuscularly, intravenously, subcutaneously, or intraperitoneally. Pharmaceutical compositions comprising a combination of plasma immunoglobulins and antigen-specific polyclonal immunoglobulins can comprise a pharmaceutically acceptable carrier, such as buffered saline, phosphate-buffered saline, or phosphate-buffered saline at a neutral pH.

[0050] Another aspect of the invention is a kit comprising an aliquot of plasma immunoglobulin, an aliquot of polyclonal antigen-specific immunoglobulin, and instructions for using the two different aliquots to treat or prevent allergic disease.

[0051] Another aspect of the invention is a kit comprising aliquots of a mixture of plasma immunoglobulin and polyclonal antigen-specific immunoglobulin, and instructions for using the aliquots to treat or prevent allergic disease.

[0052] The antibodies may be administered at any suitable site and time. However, it is preferred that the antibodies be administered simultaneously or substantially simultaneously. The antibodies may be administered sequentially as separate compositions or simultaneously or in the form of a mixture.

[0053] Example 1

[0054] Allergy test protocol for polyclonal human IMIG and polyclonal human anti-tetanus Ig

[0055] Five BALB / c mice (8 weeks old at the start of the study) were used per group. All mice except the control group (Group 1 - see below) received ovalbumin (10 μg OVA plus Al(OH)3) intraperitoneally in 0.3 ml phosphate buffered saline ("PBS") on days 0 and 14, with a further boost on day 56. From day 14 onwards, all mice received egg white solution (filtered 20% (w / v) EWS) in their drinking water.

[0056] On days -2, 7, 14, 21, 28, 35, and 42, patients receiving intramuscular immunoglobulin (Gamunex TM 25 μg Grifols) were injected intramuscularly with 0.05 ml PBS into the left gluteal muscle of mice. On days -2, 7, 14, 21, 28, 35 and 42, mice that received anti-tetanus Ig (HyperTET TM Animals receiving 25 μg of Grifols were injected intramuscularly with 0.05 ml of PBS in the right deltoid. In some cases, IMIG or anti-tetanus was absorbed with tetanus toxoid before use (x3). The control group received PBS only at the same site.

[0057] Use the following groups.

[0058] Group 1: OVA - / EWS +

[0059] Group 2: OVA + / EWS +

[0060] Group 3: Group 2 + IMIG

[0061] Group 4: Group 2 + anti-Tet Ig

[0062] Group 5: Group 2 + IMIG + anti-Tet Ig

[0063] Group 6: Group 2 + IMIG (absorbed with Tet x3) + anti-Tet Ig

[0064] Group 7: Group 2 + IMIG + anti-Tet Ig (absorbed with Tet x3)

[0065] All mice were sacrificed on study day 63. At sacrifice, anti-OVA serum IgE obtained by cardiac puncture was measured by ELISA using plates coated with 100 ng / well of OVA and developed with HRP-anti-mouse IgE and appropriate substrates.

[0066] In addition, 5x10 cells from a single animal were cultured in 2 ml of medium containing 1 μg / ml OVA. 6 Splenocytes were challenged in vitro for 72 h, and IL-2 / IL-4 were measured in the culture supernatant using a commercial ELISA kit (eBIOSciences).

[0067] result

[0068] Figure 1A showed that the combination of IMIG and polyclonal anti-tetanus Ig resulted in significant suppression of OVA-specific IgE, Figure 1B showed no significant effect on OVA-specific IgG. Figure 1A , there was no difference in the absorption of IMIG or polyclonal anti-tetanus with tetanus (groups 6 and 7). This suggests that the active pharmaceutical ingredient is not the anti-tetanus antibody.

[0069] Figure 1C Figure 5 shows a reduction in OVA-induced IL-4 levels in the spleen cells of mice from groups 5, 6, and 7 that received a combined injection of IMIG and anti-tetanus Ig. Figure 1D When considered together, it is apparent that the groups treated with IMIG plus anti-tetanus Ig (Groups 5, 6, and 7) had a lower ratio of IL-4 to IL-2 than the control groups 2, 3, and 4. This result is consistent with suppression of allergy, as shown in Figure 1A and Figure 1B middle.

[0070] Example 2

[0071] Allergy test protocol for polyclonal human IMIG and polyclonal human anti-varicella Ig

[0072] Eight BALB / c mice (8 weeks old at the start of the study) were used per group. All mice except the control group (Group 1 - see below) received ovalbumin (10 μg OVA plus Al(OH)3) intraperitoneally in 0.3 ml PBS on days 0, 14 and 42. All mice received egg white solution (filtered 20% (w / v) EWS) in their drinking water from day 14 to day 42.

[0073] IMIG (Gamunex TM 25 μg: Grifols) and anti-varicella Ig (25 μg: Grifols).

[0074] Use the following groups.

[0075] Group 1: OVA - / EWS +

[0076] Group 2: OVA + / EWS +

[0077] Group 3: Group 2 + IMIG

[0078] Group 4: Group 2 + anti-varicella Ig

[0079] Group 5: Group 2 + IMIG + anti-varicella Ig

[0080] All mice were sacrificed on study day 49. At sacrifice, anti-OVA serum IgE obtained by cardiac puncture was measured by ELISA using plates coated with 100 ng / well of OVA and developed with HRP-anti-mouse IgE and appropriate substrates.

[0081] In addition, 5x10 cells from a single animal were cultured in 2 ml of medium containing 1 μg / ml OVA. 6 Splenocytes were challenged in vitro for 72 h, and IL-2 / IL-4 were measured in the culture supernatant using a commercial ELISA kit (eBIOSciences).

[0082] result

[0083] Figure 2A showed that IL-2 production in individual splenocytes of OVA-stimulated mice was not attenuated. Figure 2B These results are consistent with the study conducted in Example 1 using a combination injection of IMIG and anti-tetanus Ig (see Figure 1C and Figure 1D ).

[0084] Example 3

[0085] Allergy testing protocol using polyclonal human IMIG and polyclonal human anti-tetanus Ig or polyclonal dog Ig and dog anti-rabies Ig using peanut butter-sensitive beagle dogs

[0086] In an improvement of the protocols of Examples 1 and 2, the inventors considered whether they could attenuate allergic sensitization in large animals (beagles) where previous literature reports have shown a high incidence (>80%) of allergic sensitization induced by topical application of peanut butter.

[0087] Animals received weekly local exposure to peanut butter (abdomen), with the first exposure occurring 1 week before treatment. The next 5 peanut butter exposures were 5 weekly treatments with combined dog Ig (IMIG and pooled dog anti-rabies immune Ig) or with combined human Ig (IMIG and anti-Tet Ig). After 5 weekly treatments, all animals were treated again with the same Ig mixture 3 times at 14-day intervals. Finally, all dogs received oral challenges with peanut butter, and serum IgG, serum IgE, and peanut butter-induced IL-2 / IL-4 production were measured.

[0088] Dogs receiving dog intramuscular immunoglobulin (Innovative Research, USA) were given 1 mg / kg intramuscularly in 0.5 ml PBS in the gluteal muscle, and dogs receiving pooled dog anti-rabies immune Ig (prepared from pooled dogs re-immunized with rabies vaccine) were given 1 mg / kg intramuscularly in 0.5 ml PBS in the contralateral gluteal muscle.

[0089] Receive human intramuscular immunoglobulin (Gamunex TM Dogs receiving human anti-tetanus Ig (HyperTET TM Dogs with 1 mg / kg of leukopenia (Grifols) were given an intramuscular injection of 1 mg / kg in 0.5 ml PBS in the contralateral gluteal muscle.

[0090] result

[0091] Figure 3A and Figure 3B Comparison of total serum IgG levels at the beginning (t0) and end (t1) of the study are shown, respectively. Figure 3C and Figure 3D Comparison of total serum IgE levels at the start (t0) and end (t1) of the study are shown, respectively. Although there were no significant changes in IgG levels, a reduction in IgE levels was observed with treatment with dog IMIG and dog anti-rabies Ig, as well as with treatment with human IMIG and human anti-tetanus Ig.

[0092] Figure 3E and Figure 3F Comparison of IL-2 production by concanavalin A (ConA) in dog peripheral blood lymphocytes (PBL) before (t0) and after (t1) treatment is shown, respectively.

[0093] Figure 3G and Figure 3H Comparison of IL-4 production by Con-A in dog PBL before (t0) and after (t1) treatment is shown, respectively.

[0094] Fig. 3I Comparison of IL-2 / IL-4 induction by ConA in dog PBL before / after Ig treatment is shown. Note that even for this polyclonal response, the IL-2 / IL-4 ratio in dogs was increased after treatment with dog IgG or human IgG (*, p<0.05).

[0095] Figure 3J It was shown that IL-2 and IL-4 production by peanut butter stimulated dog PBLs after treatment with dog IMIG and dog anti-rabies Ig and after treatment with human IMIG and human anti-tetanus Ig. Figure 3K The IL-2:IL-4 ratio after treatment is shown. Consistent with other experiments, IL-4 production was attenuated by Ig treatment, but not IL-2 production. In addition, the IL-2:IL-4 ratio was increased after treatment (*, p<0.05).

[0096] Embodiment 4:

[0097] Dose-response studies – polyclonal human IMIG and polyclonal human anti-tetanus Ig in pre-immunized mice

[0098] The inventors also performed dose response studies using polyclonal human IMIG and polyclonal human anti-tetanus Ig in pre-immunized mice.

[0099] In the dose response study, all groups had five BALB / c mice each. Mice were approximately 25 grams. All mice received OVA (10 μg OVA plus Al(OH)3) on days 0 and 14, and a boost on day 56. All mice received EWS (filtered 20% (w / v) egg white solution in their drinking bottles) starting on day 14.

[0100] On days 56, 63, 70, 77, and 84, mice began to be treated with immunoglobulin injections.

[0101] The following groups were used:

[0102] Group 1 (control): OVA immunization and EWS

[0103] Group 2: Group 1 + IMIG (250 μg / mouse) + anti-Tet Ig (10 μg / mouse)

[0104] Group 3: Group 1 + IMIG (250 μg / mouse) + anti-Tet Ig (50 μg / mouse)

[0105] Group 4: Group 1 + IMIG (250 μg / mouse) + anti-Tet Ig (250 μg / mouse)

[0106] Group 5: Group 1 + IMIG (50 μg / mouse) + anti-Tet Ig (10 μg / mouse)

[0107] Group 6: Group 1 + IMIG (50 μg / mouse) + anti-Tet Ig (50 μg / mouse)

[0108] Group 7: Group 1 + IMIG (50 μg / mouse) + anti-Tet Ig (250 μg / mouse)

[0109] Group 8: Group 1 + IMIG (10 μg / mouse) + anti-Tet Ig (10 μg / mouse)

[0110] Group 9: Group 1 + IMIG (10 μg / mouse) + anti-Tet Ig (50 μg / mouse)

[0111] Group 10: Group 1 + IMIG (10 μg / mouse) + anti-Tet Ig (250 μg / mouse)

[0112] Group 11: Group 1 + IMIG (50 μg / mouse) + anti-Tet Ig (50 μg / mouse) + intraperitoneal injection of CoQ10 (100 μg / mouse) every 2 days from day 56 to day 90

[0113] Group 12: Group 1 + IMIG (250 μg / mouse)

[0114] Group 13: Group 1 + anti-Tet Ig (50 μg / mouse)

[0115] A final boost with OVA was given on day 90, and mice were sacrificed on day 97.

[0116] Serum OVA-specific IgG / IgE was measured by ELISA. In addition, 2x10 6 Splenocytes were challenged in vitro for 72 h, and IL-2 / IL-4 were measured in the culture supernatant using a commercial ELISA kit (BioLegend).

[0117] result

[0118] Figure 4A and Figure 4B The optimal suppression of IgE responses was shown to occur at IMIG doses of 250 μg / mouse and 50 μg / mouse, and across a broad spectrum of anti-Tet doses (from 10 μg / mouse to 250 μg / mouse). At lower IMIG doses (10 μg / mouse), suppression was not evident. If the animals also received CoQ10 as an antioxidant (100 μg / mouse) every two days, there was a synergistic effect at lower doses of IMIG (50) and anti-Tet (50). No reduction in IgG responses occurred ( Figure 4B ).

[0119] Figure 4C , Figure 4D and Figure 4E Use IL-4 and IL-2 production as readout to confirm Figure 4A and Figure 4B Data were obtained from the literature. At IMIG doses of 250 μg / mouse and 50 μg / mouse, as well as a broad spectrum of anti-Tet doses (from 10 μg / mouse to 250 μg / mouse), inhibition of IL-4 production was again observed, but no inhibition of IL-2 production was observed. At the lower IMIG dose (10 μg / mouse), inhibition was not significant. If the animals also received CoQ10 as an antioxidant (100 μg / mouse) every 2 days, there was a synergistic effect at the lower doses of IMIG (50) and anti-Tet (50). Figure 4E These data are further emphasized by comparing the IL-2:IL-4 ratio as shown.

[0120] In the foregoing description, exemplary modes for implementing the present invention have been described in terms of embodiments. However, the scope of the claims should not be limited by those embodiments, but should be given the broadest interpretation consistent with the entire specification. Therefore, the description and drawings should be considered illustrative rather than restrictive.

Claims

1. Use of a combination of pooled plasma immunoglobulins and antigen-specific polyclonal immunoglobulins in the preparation of a medicament for treating or preventing allergic diseases, wherein the antigen-specific polyclonal immunoglobulins are prepared immunoglobulins with a high number of antibodies against a specific pathogen or against a specific antigen; wherein the antigen-specific polyclonal immunoglobulin is selected from the group consisting of polyclonal anti-tetanus toxoid immunoglobulin, polyclonal anti-rabies immunoglobulin and polyclonal anti-varicella immunoglobulin; and wherein said pooled plasma immunoglobulins and said antigen-specific polyclonal immunoglobulins are from the same species.

2. The use according to claim 1, wherein the pooled plasma immunoglobulins are intramuscular immunoglobulins.

3. The use according to claim 2, wherein the intramuscular immunoglobulin is human intramuscular immunoglobulin.

4. The use according to claim 1, wherein the pooled plasma immunoglobulins are human plasma immunoglobulins.

5. The use according to claim 1, wherein the pooled plasma immunoglobulins are from a non-human species.

6. The use according to claim 1, wherein the dose of the pooled plasma immunoglobulin is greater than 50 mg / kg body weight.

7. A combination of pharmaceutical compositions for treating or preventing allergic diseases, the combination of pharmaceutical compositions comprising: Pooled plasma immunoglobulins; and Antigen-specific polyclonal immunoglobulins, The antigen-specific polyclonal immunoglobulin is an immunoglobulin prepared with a high number of antibodies against a specific pathogen or against a specific antigen; wherein the antigen-specific polyclonal immunoglobulin is selected from the group consisting of polyclonal anti-tetanus toxoid immunoglobulin, polyclonal anti-rabies immunoglobulin and polyclonal anti-varicella immunoglobulin; and wherein said pooled plasma immunoglobulins and said antigen-specific polyclonal immunoglobulins are from the same species.

8. The combination of pharmaceutical compositions according to claim 7, wherein the pooled plasma immunoglobulins are intramuscular immunoglobulins.

9. The combination of pharmaceutical compositions according to claim 8, wherein the intramuscular immunoglobulin is human intramuscular immunoglobulin.

10. The combination of pharmaceutical compositions according to claim 7, wherein the pooled plasma immunoglobulins are human plasma immunoglobulins.

11. The combination pharmaceutical composition according to claim 7, wherein the pooled plasma immunoglobulins are from a non-human species.

12. The combination of pharmaceutical compositions according to claim 7, wherein the dose of the pooled plasma immunoglobulins is greater than 50 mg / kg body weight.

13. A kit comprising aliquots of pooled plasma immunoglobulins, aliquots of antigen-specific polyclonal immunoglobulins, and instructions associated with the kit directing the use of the aliquots of pooled plasma immunoglobulins and the aliquots of antigen-specific polyclonal immunoglobulins for treating or preventing allergic diseases, wherein the antigen-specific polyclonal immunoglobulins are prepared with a high number of antibodies against a specific pathogen or against a specific antigen; wherein the antigen-specific polyclonal immunoglobulin is selected from the group consisting of polyclonal anti-tetanus toxoid immunoglobulin, polyclonal anti-rabies immunoglobulin and polyclonal anti-varicella immunoglobulin; and wherein said pooled plasma immunoglobulins and said antigen-specific polyclonal immunoglobulins are from the same species.

14. A kit comprising aliquots of a mixture of pooled plasma immunoglobulins and antigen-specific polyclonal immunoglobulins, and instructions associated with the kit directing the use of the aliquots of the mixture of pooled plasma immunoglobulins and antigen-specific polyclonal immunoglobulins for treating or preventing allergic diseases, wherein the antigen-specific polyclonal immunoglobulins are immunoglobulins prepared with a high number of antibodies against a specific pathogen or against a specific antigen; wherein the antigen-specific polyclonal immunoglobulin is selected from the group consisting of polyclonal anti-tetanus toxoid immunoglobulin, polyclonal anti-rabies immunoglobulin and polyclonal anti-varicella immunoglobulin; and wherein said pooled plasma immunoglobulins and said antigen-specific polyclonal immunoglobulins are from the same species.

15. A pharmaceutical composition comprising the following combination: Pooled plasma immunoglobulins; and Antigen-specific polyclonal immunoglobulins, The antigen-specific polyclonal immunoglobulin is an immunoglobulin prepared with a high number of antibodies against a specific pathogen or against a specific antigen; wherein the antigen-specific polyclonal immunoglobulin is selected from the group consisting of polyclonal anti-tetanus toxoid immunoglobulin, polyclonal anti-rabies immunoglobulin and polyclonal anti-varicella immunoglobulin; and wherein said pooled plasma immunoglobulins and said antigen-specific polyclonal immunoglobulins are from the same species.

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