JPH0334935A - Anti-tryptase antibody and acquired immunodeficiency syndrome therapeutic agent using the same - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to an anti-tryptase antibody and a therapeutic agent for acquired immune deficiency syndrome using the anti-tryptase antibody, and more specifically relates to an anti-tryptase antibody and a therapeutic agent for acquired immune deficiency syndrome using the anti-tryptase antibody. The present invention relates to an anti-tributase antibody that specifically reacts with anti-tryptase antibodies, a therapeutic agent for acquired immunodeficiency syndrome containing the anti-tryptase antibody as an active ingredient, and a peptide 1 Noctin for acquired immunodeficiency syndrome consisting of tryptase.

[Prior Art] Acquired immunodeficiency syndrome
tln.

de4icience syndrome: AI
DS) is human immunodeficiency virus (HIV)
This is a serious immunodeficiency disease caused by cancer, which is currently spreading worldwide, and the development of a therapeutic drug or vaccine is desired.

Mouth 1, the virus that causes AIDS, is a type of retrovirus that has RNA as its gene, and specifically,
Human immunodeficiency virus 1 from lymphocytes of lymphadenoma patients
Human immunodeficiency virus type 2 (RO IV-1) and human immunodeficiency virus type 2 (RO IV-2) have been isolated from AIDS patients in West Africa [Hireidlle et al., Nat.
ure 326, 662 (1987)l.

Oral IV binds to helper 1 cells, which are a type of immunocompetent cell, invades the cells, kills helper T cells, and causes immunodeficiency. l-11V
infection is caused by gp12, which is the enveloped white matter of HIV.
D
algleis et aNature 312.7
63 (1984); Klatzmann et a.
l,, Nature 312.767 (1984
): Hcl)ouoal at al,, 5c
ience 231.

382 (1986) 1゜Based on this knowledge of the infection mechanism, it has been proposed to use antibodies against 1.11) 120 as an HIV infection inhibitor [Ro.
bey et al., Proc. Natl., A.
cad, Sci, ll5A83.7023 (19
86)].

Historically, monoclonal antibodies against opi20
) When we economized on the reactivity with various synthetic oligopeptides containing a part of the amino acid sequence constituting 120, we found that gp
It has been reported that the monoclonal antibody reacted only with a synthetic oligopeptide corresponding to amino acids 308-331 [1] from the N-terminus of 120 [Hatsush
ita et at,, J, Vir.

(32, 2107 (1988)).

Conversely, various oligopeptides containing the - part of the amino acid sequence that constitutes gp120 were synthesized and antibodies against each were created.
It has been reported that an antibody to a synthetic oligopeptide corresponding to amino acid ``-321st'' had the ability to inhibit syncytium formation, which is an indicator of inhibition of eye IV infection [Pa1
Ker et al., ProcNatl, Aca.
d, Sci, USA 85.1932 (198
8)]. On the other hand, it is known that this region corresponding to amino acids 303-321 from the N-terminus is not a region involved in binding between 0p120 and CD4 [Kowalski et al., 5science].
237.

1351 (1987); La5ky et at,
, Ccll 50 975 ('1987)]. Therefore, by binding to bgp120 with an antibody directed against a region of the gp120 molecule other than the region that is completed when it binds to CD4, the three-dimensional structure of gp120 is modified.
It is also possible to think that it inhibits the binding of 20 to CD4. However, regions other than the above-mentioned regions, such as gf) 5 from the N-terminus of 120 (L/l-518 No.
It has been reported that an antibody raised against a synthetic oligopeptide corresponding to the 7-mino acid 1" reacted with gp120 itself, but did not have the ability to inhibit syncytium formation [ Pa1ker et at Proc,
Natl, Acad, Sci, ll5A
Bb, 1 932 (1988) 1゜ From these facts, in the 00120 molecule, for example, the region corresponding to the 504th-518th nonomimino acid from the N-terminus, and the 1-1 region corresponding to the 303rd-321st or 308-331st
Comparing the regions corresponding to the amino acids of
Since the binding with /I was inhibited, it is possible that the posterior region is deeply involved in the binding of both. This region is called the phase change region and is clinically isolated from fil-11V.
This is a region in which amino acid sequence differences are often found between

On the other hand, one of the new B1'ase inhibitors has recently been developed in rats. Trypstadin has been isolated and purified from full cells, and its primary structure has been determined.
et al., J. Biol. Chem.
263.1810/1-(1988): Kido et al., Cell Engineering, 851 (1988): Kido et al. 1 Metabolism 25. Special issue “Metabolic disease highlights” 187 (1988) 1
Tributadine is a specific inhibitor of tryptase, a new trypsin-type hylin protease. Triplitase is a tetramer consisting of selymp [1 tearpi] of molecule fil 40,000 and 1.1 nits of molecule ff 135,000 isolated and purified from the granules of rat mast cells [KidoaArch, Bioch.
em, Biophys, 239.436 (19
85); Kido et al. 1 Metabolic Disease Special Issue ``Metabolic Disease Highlights'' M87. (1988)].

The physiological actions of trypstadin and tryptase include:
It is known that tryptase catalyzes the conversion of prothrombin to α-thrombin in the blood coagulation system, and that trypstadin inhibits this action, and that this enzyme is deeply involved in the development of allergic inflammation. Irushi Kido et al. 1 Metabolism 2 Mutual, Extraordinary Increase 111 Sea)゛Metabolic Disease Highlight 1
To” 187 (1988); Kido et al., Cell Engineering, 851
(1988) Ko. However, tribustatin and 1-ributase are the pathogenic viruses of AIDS.
It is not known at all how to produce V.

[Problems to be Solved by the Invention] An eleventh object of the present invention is to provide an anti-tryptase antibody that specifically reacts with i~liptase.

Another object of the present invention is to provide an AIDS therapeutic agent comprising the anti-tryptase antibody as an active ingredient, and an AI comprising tryptase.
The purpose is to provide one pair of DS vaccine.

[Means for solving the problem] The present inventor (1-11)
We focused on the variable region of Qp120, which is thought to be deeply involved in the binding between 120 and the CD4 antigen molecule of helper F cell surface m1, and found that Gly-Pr is a relatively well conserved sequence.

The sequence Gly-ArQ-Ala-Phe was discovered. This sequence in the I variable region is Op”l 2
It is thought to be deeply involved in the binding between GPL 20 and CD4, and the substances that have a similar sequence to this sequence are gpl 20 and C
It is expected to inhibit binding to D4.

The present inventor investigated the ability to inhibit syncytium formation, which is an indicator of inhibition of l-11V infection, and found that trypstatin has a strong ability to inhibit syncytium formation. Find out what you are doing.

Therefore, there is an enzyme like 1-liptase that is inhibited by 1-lipstadin on the cell surface, and this enzyme
Since it was suggested that tryptase is deeply involved in the infection of 11V cells, it was considered that antibodies against tryptase may also have a similar suppressive ability. Therefore, as a result of intensive studies on the ability of anti-tryptase antibodies to suppress syncytium formation, which are produced by immunizing animals with tryptase, the present inventor found that anti-tryptase antibodies have a strong ability to suppress syncytium formation.
The present invention has been completed based on the discovery that Tributarpi itself can be used as a vaccine against AIDS.

That is, the present invention provides an anti-1-riptase antibody that specifically reacts with tryptase or a fragment 1-- that includes an antigen-binding site thereof: an anti-1-riptase antibody that specifically reacts with tryptase or a fragment that includes an antigen-binding site thereof. AIDS therapeutic agent containing 1 to 1 as active ingredients; and AIDS J44 peptide vaccine consisting of tryptase.

The anti-tryptase antibody of the present invention can be obtained from the serum of an animal immunized with tryptase.

The tryptase used here has approximately 35°00 υbuunits.
0-4 is a trypsin-type proteinase with a molecular weight of approximately 14.0.000, which can be isolated and purified from, for example, human lung mast cells, peritoneal mast cells, etc. It can be done [Kido et aJ, Biol,
Cham, 256. 11939 (1981)
: Kido et at...
, Biochem, Biophys, p.

39.436 ('1985)]. Furthermore, as shown in Example 1, it can also be obtained from rat tongue mast cells. Tryptase can be isolated and purified, for example, from homogenates of tongue, peritoneum, lung, etc., by using means such as column chromatography using S-sepha[1-se, arginine senoalose, abrotinin senoalose, etc. I can do it. The tryptase referred to herein is not particularly limited, and may be obtained from any animal, or may be obtained using I11 recombinant DNA technology.

Any animal may be used to immunize with tryptase, such as rabbits, mice, sheep, horses, etc. Immunization is performed by intradermally administering tryptase and a complete adjuvant of 70 in 1 to 70 in 1 multiple times at regular intervals. After immunization,
Anti-tryptase antibodies can be prepared by collecting serum and obtaining IgG fraction by, for example, ammonium sulfate fractionation or D E b 2 column chromatography. Alternatively, 0 ethanol fractionation [Cohn et al., J.
Am, ChemSoc, Dandan, 459 (1946
)] to obtain a fraction containing gamma globulin from serum,
The IqG fraction can then be obtained by precipitation with polyethylene glycol, ethanol, etc. [5ch
Ultze et al., “Mo1ecular B
ioloay of Human ProteinS”,
Elsevier, AIIlsterdam 2.
256 (1966)].

The anti-1-ributase antibody of the present invention may be a monoclonal antibody, and such a monoclonal antibody can be prepared by the method of Kohler and Milstein.
Nature 256.4.95 (1975).

That is, lung cells were obtained from an animal immunized with tryptase,
Monoclonal antibodies can be obtained by fusing this with myeloma cells to obtain hybridomas and culturing them in vivo or in vitro.

Furthermore, in order to reduce the antigenicity of the monoclonal antibody,
It is also possible to use chimeric antibodies in which the variable region 1 is derived from a mouse antibody and the constant region is derived from a human antibody, which can be produced by known methods [Sahag et al.
An at al, J. Immunolo(IV
137, 1066 (1986); NishN
15hi et al, CancerResearch
h Raw 7.999 (1987): Riechman
n et al., Nature 332, 323
(1988)].

The anti-tryptase antibody of the invention may be a fragment containing its antigen-binding site, for example by treating the antibody with pepsin [N15onoff et a^rch,
Biochem, Biophys, 89.230
(1960); Hizuka at al.
J, Immunolo (1120°800 (19
78)], "(ab')2 can also be used as a fragment and treated with papain to produce [R,R,Porte
r, Bioche LIlical Journal
73.

119 (19!:)9)1, may be a Fab fragment.

Anti-tryptase antibody or fragment thereof is 1-1
The present inventors have revealed that this method strongly suppresses 1 V infection. That is, human acute lymphoblastic leukemia cells, MOL T-4 cells (ATCC
C, which is a leukemia cell similar to No. CRL-1582)
CRF-CE M cell (ATCC?Ji No.CCL-11
9) LAV-1 [Barre-3
inoussi et al,,5science 22
0, 868 (1983) OE persistently infected with 1
When M/ShA V-1 is cultured together, syncytia, which is an indicator of 1-11 V infection, are formed, and anti-1
When the anti-tryptase antibody or its fragment was added and similarly cultured, the formation of syncytia was suppressed, and therefore the anti-tryptase antibody or its fragment was
It was confirmed that it suppresses V infection.

Therefore, the anti-tryptase antibody or fragment thereof of the present invention is extremely useful as a therapeutic agent for AII)S.

Anti-tryptase antibodies or fragments thereof are
Depending on the patient's needs, it can usually be administered intravenously, intramuscularly, subcutaneously, etc. by one administration.

Preparations for non-shuttle administration (1) include injections.

3. Injections can be prepared by subjecting the IQG fraction or its fragments 1 to 1 to obtained as described above to dialysis or sterilization by filtration, if necessary, and dissolving or dispersing them in an aqueous medium.

Furthermore, in order to further increase the purity, it is also possible to use an IQG fraction or a fragment thereof that has been further purified using an affinity column adsorbing tryptase. Mannitol, lactose, albumin, etc. can be added to the injection as appropriate.

Further, commonly used preservatives, stabilizers, preservatives, surfactants, etc. can be added as necessary.

The dosage of the pile tryptase antibody or its fragment may vary depending on the patient's age, weight, symptoms, etc., but usually, the dose of the IOG or its fragment is 20 to
2,000 ■ / 9 body weight / day, preferably 50-1.0
OOIyJ/l (g body weight/day).

As is clear from the detailed explanation above, by immunizing an animal with tryptase, 4 anti-1 to ribtase antibodies can be produced in v+vo, and this anti-tryptase antibody strongly suppresses 111V infection. From this fact, it will be clear to those skilled in the art that trizotases can be used as peptide vaccines for AIDS.

When tryptase is used as a vaccine for human AIDS patients, it is desirable to use tryptase produced in animals such as rats in view of its antigenicity.

As a tryptase vaccine preparation, 1-liptase itself may be used alone, or an adjuvant may be added as an auxiliary agent. Examples of such adjuvants include aluminum hydroxide, aluminum phosphate, calcium phosphate, and derivatives of muramyl dipebdide, which is a constituent of the cell wall of Mycobacterium tuberculosis.

Tryptase as a vaccine (as in the case of anti-trizotase antibodies, it can be administered parenterally, usually intravenously, intramuscularly, or intradermally.The dose is:
Tryptase per dose 5 0.2-20 μg/body weight 9, preferably 1-10 μg
/body weight in kg.

[Effects of the Invention] Anti-tributase antibodies that specifically react with tryptase have the effect of strongly suppressing l]lV infection;
It is extremely effective as a therapeutic agent for AIDS. Since tryptase induces the production of anti-tryptase antibodies in vivo, and anti-tryptase antibodies strongly inhibit oral IV infection, tryptase can be used as a vaccine for AIDS.

[Example] The present invention will be specifically described below with reference to Test Examples and Examples.

Example 1 Preparation of anti-tryptase antibodies and fragments thereof ■ Preparation of tryptase Method of Kido et al. [Kido et al., Arch.
ives of Biochem, and Bioph
ys, 239.436 (1985) 1.

6 20 (f [0.1 M potassium phosphate loose!
Solution J (pH 8.0>) was added to make a small sample, and acetic acid was added to the centrifuged supernatant to adjust the pH to 4.5. Ammonium sulfate was added to the supernatant from which the generated precipitate was removed, and the mixture was centrifuged. The precipitate was dialyzed against 50+nH acetate buffer (pH 14,5). This was adsorbed onto S-Sepharose (manufactured by Pharmacia) and diluted with 50mM acetate buffer (pH 4,5)/NaCl.
It eluted at (0→IM>).

The active fraction was adsorbed onto Blue Sepharose (manufactured by Noalmacia), and 20+nH acetate buffer (pH 4, 5)/N
Elution was performed with aCl (0→1M). After adjusting the pH of the active fraction to 6.5, 110 liters of CaCl2 was added and adsorbed onto arginine Sepharose (manufactured by Noal 7 Shea). 50 mHTris, IICl (pH 6,
5)/10 mHCaCl2/NaCl (0→1M). After concentrating the active fraction using an ultrafilter, the liquid filter [
1. It was purified using Madographie (G3000SW manufactured by Toyo Sodatsu Co., Ltd.).

From the elution position of liquid chromatography and the electrophoresis pattern of SDS polyacrylamide gel electrophoresis [Laemm 7 Nature 227.680 (1970)], tryptase from rat tongue Yamaki is considered to be a tetramer consisting of sub-1 nit with a molecular weight of approximately 35,000. Ta.

■ Preparation of anti-tryptase antibody 1, anti-tryptase serum made by i1gJ 100μ9 of tryptase obtained by the above method (0,1
d) was well mixed with Freund's complete adjuvant (0.5) and 0.15 (0.15) was subcutaneously injected into each rabbit's paws.

Tributa zero after 3 weeks.

μ9 was also mixed with Freund's complete adjuvant,
The same rabbits were given sarcastic injections in the same manner. After a further 3 weeks, 1 to Lipta-Zero 0μ9 were similarly injected subcutaneously into rabbits. Blood was collected 4 days after the final immunization and serum was prepared.

2. Add 4 times the amount of P to the rabbit anti-tributase serum obtained in Preparation 1 of anti-tryptase I (IIG).
BS (50mM phosphate buffer (pH 7,2) 10.18
36% sodium 1a acid was added in an amount equal to the total amount, and the mixture was further stirred at room temperature for 30 minutes and 8 hours. Centrifuge at 12,000Xg for 20 minutes, and add the precipitate to a small amount of 50 IM phosphate buffer (pH 7,6) 10.158
Suspended in NaCl. Add this to Ur 1 ~ [1 Gel AcA
341LK13) was passed through.

The fractions in which IQG was eluted were collected and added to 10 mHTris.

1-ICl (p118.0) was dialyzed overnight at 3°C. This was adsorbed onto DE52 (Whatman), 10 mHTris, l-t Cl (Dl18
, O), 10 mHTris, mouth Cl.
(DH8,0>/NaCl (OmH→100mM)
Elute with ζ. Both fractions in which ICIG was eluted were collected and concentrated using an ultrafilter. The presence of IQG in this fraction was confirmed by 5DS-polyacrylamide gel electrophoresis [1ae
mmli, Naturc 227.680 (197
0)]. In addition, the temperature of the antibody was 527μSi/
In! ! ,Met.

■Properties of anti-tryptase IQG 1. Confirmation of the reactivity of anti-tryptase IgG and tryptase using the Ochterlony method■.It is clear that the purified anti-tryptase 10G obtained in 2.
1ler OV, Vl, 30 (1962)]. Agarose was dissolved in PBS to a concentration of 1% (w/v), poured onto a glass plate, and solidified. Next, make a hole with a puncher, dispense the antibody and purified tributase, and leave it at room temperature for several hours. A sedimentation line was observed between the well containing anti-tryptase ICIG and the well containing purified tryptase. I was able to do that.

No precipitation line could be observed between the well containing lq('+) purified from non-immune rabbit serum and the well containing purified tryptase. It did not react with trypsin from the source.

28 Confirmation of the reactivity of anti-tryptase ICIG and tributase using Western plotting method It is confirmed that the purified anti-tryptase I (IG) obtained in 1.2 reacts with tryptase using Western plotting method [To
wbin et al., ProcNatl, Ac.
adi, Sci, USA76.4350 (1979
)] was also *g. Purified tributase was fractionated by 5DS-polyacryl 7 midgel electrophoresis and electrophoretically nitrotransferred in a buffer with the composition of 25 mHTris, t'Cl/192nrf4 glycine (pt+8.3>/20% methanol). 1- on the relurose membrane
I ransfered. r B S (50m14 Tr+
s, l-I C (pH 8, o) / 150 mH NaC
After blocking overnight in l)/10% C8 at room temperature, anti-l-ributase IgG diluted in 8871% 8S8 (bovine blood septic albumin) was bound for 5 hours at room temperature.

1'Bs10.05%Twecn 20 Te? Ha
After repeating 5 minutes of washing 5 times, S T RA 1
'AGENE IE's PicoBlue II
The protein band bound to the antibody was detected using I1 munodetection kit. As a result, it was confirmed that anti-tryptase IgG reacted with purified 1-liptase.
C ki Iko. Furthermore, anti-tryptase IgG did not react with 1-ribusin derived from bovine and human kidneys.

Preparation of F(ab'>2 from IV, anti]-liptase antibody Anti-1-sbuter txoG was digested with pepsin to prepare -(1 F(ab')2) [N15onoff
t aArch, Biochem, Bioph
ys, 89. 230 (1960); Han
dy et al,, J old of, Chcm,
238.206 (1963)]. Anti-tryptase [QG
1/50 ffi (7) Hel Shinwoka'x,
0.1) 1 vinegar 11i loose wIJwJ liquid (1) 114.5)
Digestion was performed for 18 hours at 37°C.

After adjusting the pl+ to 8.0 by dropping IN Na0 into the reaction solution, centrifuge to remove insoluble matter, and add sodium sulfate to the supernatant to a final concentration of 0.18 g/d to obtain a precipitate. Ta. This precipitate was collected at 50mHTr+S port CI (DII8
．． Seno7dex G150 (manufactured by Pharmacia) dissolved in O>/150mH NaCl and equilibrated with the same buffer
was passed through, and both fractions in which F(ab')2 was eluted were collected.

It was confirmed by the method shown in I[[-1* that this "(ab')2 reacts with tryptase in the same way as anti-tryptase IgG.

<Test example> +11 V infection inhibition test 1, cells used 2 Human acute lymphoblastic leukemia cells, MOL T4 cells (AICC number CRLC1582) and CCRF −
Cl3M cells (A1- CC number CCL-119)
L AV-1 [Barr
e-3inoussi at al,,5science
220.868 (1983)] caused persistent infection.
EM/L AV-1 cells were used.

2. Cell culture Cells were cultured in R1) M11640 medium supplemented with 10% FC3 at 37°C, 5% CO, and 95% relative humidity.

3. Syncytium formation inhibition test (1) Method The syncytium formation inhibition test was conducted according to the method of Lifson et al. [Lifson et al., J. Exp. R.
ed, 164.2101 (1986)]. MOL
A portion of the T-4 culture medium was centrifuged at 200 rpm for 5 minutes to collect the cells, the supernatant was removed (), and the cells were transferred to A.
The cells were suspended in SF 104 medium (manufactured by Ajinomoto Co., Ltd.) and the number of cells was adjusted to 5 x 10'/cell. This cell suspension was added with an antibody concentration of 527μ/- as determined in Example 1, ■ and 2.
Various concentrations of anti-tryptase IOG obtained by diluting anti-tryptase IQG at various ratios, or F (ab'> 2) of anti-tryptase IQG were added to obtain a cell concentration of 1×.
The mixture was dispensed into a 96-well microtiter plate (105/well) and left at 37°C for 30 minutes. The antibody was diluted in advance with ASF104 medium (manufactured by Ajinomoto Co., Ltd.) and then dialyzed against the same medium overnight at 4°C. To this OEM/LAV-1 thin 111 (Illlltl1 degree 1
x 107/d), mix well, and heat at 37°C.
The cells were cultured in 5% CO2 for 12 hours, and each well was observed at 200 cells using an inverted microscope. When syncytium formation is inhibited by more than 60%, it is designated as 4-+, when it is inhibited by more than 30% and less than 60%, it is +, when it is inhibited by less than 30%, it is designated as -, and when it is not inhibited at all, it is designated as -. The ability to suppress cell formation was evaluated.

(2) Results The evaluation results for the ability to inhibit syncytium formation are shown in the table below.

4. Ability of anti-tryptase 1gG to inhibit syncytium formation As described above, anti-tryptase IoG inhibited syncytium formation in a concentration-dependent manner. Anti 1~Riptar 1! IQG's F(a
A similar degree of inhibition of syncytium formation was also observed when b')2 was added. However, no inhibition of syncytium formation was observed with IQG purified from the serum of non-immune rabbits.

Example 2 Injection 1 of Anti-1 to Liptarpi Antibodies Preparation of Affinity Column 1 mHI-ICI was added to one volume of activated Cl-1-t Phallose 4B (manufactured by Pharmacia) to swell it, and the mixture was washed. Purified tryptase 200μq(0,1)IN
aHCO3 (pH 8, O > solution) was added and mixed with the swollen gel and mixed between IIZt at room temperature., 50n
+HTris, 1-ICI (pH 8, O) 10.
After washing the gel with 5H NaCl, it was resistant to 50 mH citric acid. Jum (pH 4,0) 10.58 NaC
Washed with l. This washing operation was repeated three times.

2. Anti-tryptase Io using affinity column
II of Example 1 was added to the affinity column prepared in Purification 1 of G.
After washing by passing a solution containing anti-tributase IQG prepared in the same manner as in 2, anti-tryptase I bound to the column with 0.1H phosphate buffer solution (pHio, 8)
QG was eluted. After immediately adjusting the pt+ of this solution to 7.5, it was filtered to 111i! The mixture was filtered, dialyzed, and lyophilized to prepare a 16% aqueous solution.

When anti-1 helibutase IqG purified in this manner was tested for its ability to inhibit syncytium formation by the method shown in the test example, activity was found.

3. Preparation of anti-tryptase antibody injection 2. tf'i
An injection was prepared by preparing Anti-1 to Liptar 121gG according to a known injection manufacturing method, and adding glycine as a stabilizer and methyl thiolate as a preservative.

6 Dosage is 20-20 as IoG or its fragment
00 ■ / 9 body weight / day, preferably 50-1000 #I
g/l (g body weight/g mouth muscular) l.

Example 3 Preparation of anti-AIDS vaccine Rat tryptase purified in the same manner as in Example 1 (2) was dialyzed against water and freeze-dried to obtain an AIDS vaccine.

The basic rule is to dissolve it in physiological saline and send it under the skin. The dose is 0.2-20μ as tryptase per time.
fj/9 body weight, preferably 1 to 10 μ'j/9 body weight.

When this solution was administered to rabbits using the method shown in Example 1, 1.1, and examined using the method shown in Example 1, 1.2, the production of antibodies was confirmed at N1.

Claims (3)

[Claims] (1) An anti-tryptase antibody that specifically reacts with tryptase or a fragment thereof containing an antigen-binding site. (2) A therapeutic agent for acquired immunodeficiency syndrome whose active ingredient is an anti-tryptase antibody that specifically reacts with tryptase or a fragment thereof containing an antigen-binding site. (3) A peptide vaccine for acquired immunodeficiency syndrome consisting of tryptase.