CN1480215A - Compound antibody vaccine of SARS virus antigen as well as its model of experimental animal and method - Google Patents
Compound antibody vaccine of SARS virus antigen as well as its model of experimental animal and method Download PDFInfo
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- CN1480215A CN1480215A CNA031462316A CN03146231A CN1480215A CN 1480215 A CN1480215 A CN 1480215A CN A031462316 A CNA031462316 A CN A031462316A CN 03146231 A CN03146231 A CN 03146231A CN 1480215 A CN1480215 A CN 1480215A
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Abstract
A SARS virus antigen-antibody vaccine and its experimented method are disclosed. Said composite vaccine is prepared from the SARS virus antigen and specific antibody, and features that it can directly submit said virus antigen to the antigen presenting APC cells and mononuclear/macrophage for exciting the immune response mechanism of lymphatic immune system. Its advantages are high immune effect and specific target treatment to SARS.
Description
Technical field
A kind of SARS virus antigen-antibody combination vaccine and experimental technique have been the present invention relates to.It is the combination vaccine of SARS virus antigen and specific antibody; it can directly be virus antigen passs antigen presentation APC cell Monocytes; excite the immunne response mechanism of lymphocytic immunity system; shorten the immune defence protection mechanism and induce the provocative reaction time; improvement is reactionless at the SARS vaccine; the low reaction crowd excites immune response at inducing of SARS vaccine; can be for reactionless at the SARS vaccine; low immunoreation crowd; with asymptomatic SARS virus the infected; effective anti-SARS virus infection immunity defence protection is provided, and has the special specific aim therapeutical effect that anti-SARS virus infects.And the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine.
Background technology
Tradition inactivated vaccine and modern subunit antigen protein vaccine need induce the provocative reaction time to produce more firm immunity at human body through repeatedly inoculation, long humoral immunization mechanism, therefore the SARS virus inactivated vaccine and the subunit antigen protein vaccine of current development are unfavorable for the urgent emergent prophylactic immunization of the new epidemic situation of SARS that following prevention may take place once more in the whole world.In the human colony, have at viral inactivation vaccine and the subunit antigen protein vaccine is reactionless or the low reaction crowd; in the SARS of this generation epidemic situation, have asymptomatic SARS virus the infected; inoculation SARS virus inactivated vaccine and subunit antigen protein vaccine can not for reactionless or low reaction crowd, with asymptomatic SARS virus the infected, provide effective anti-SARS virus infection immunity defence to protect.
Summary of the invention
The invention discloses a kind of SARS virus antigen-antibody combination vaccine and experimental technique.It is the combination vaccine of SARS virus antigen and specific antibody; it can directly be virus antigen passs antigen presentation APC cell Monocytes; excite the immunne response mechanism of lymphocytic immunity system; shorten the immune defence protection mechanism and induce the provocative reaction time; improvement is reactionless at the SARS vaccine; the low reaction crowd excites immune response at inducing of SARS vaccine; can be for reactionless at the SARS vaccine; low immunoreation crowd; with asymptomatic SARS virus the infected; effective anti-SARS virus infection immunity defence protection is provided, and has the special specific aim therapeutical effect that anti-SARS virus infects.And the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine.
The objective of the invention is; provide a kind of SARS virus antigen directly can being to pass antigen presentation APC cell Monocytes; excite the immunne response mechanism of lymphocytic immunity system; shorten the immune defence protection mechanism and induce the provocative reaction time; improvement is reactionless at the SARS vaccine; the low reaction crowd excites immune response at inducing of SARS vaccine; can be for reactionless at the SARS vaccine; low immunoreation crowd; with asymptomatic SARS virus the infected; effective anti-SARS virus infection immunity defence protection is provided, and has the SARS virus antigen-antibody combination vaccine of the special specific aim therapeutical effect of anti-SARS virus infection.And the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine.The specific antibody of virus antigen is confirmed by modern science: many kinds of human virus's property diseases are had prevention and therapeutical effect, it is the person that effectively to suppress viral infection morbidity, effectively blocking virus transmission of infection chain, short-term antiviral infection immunity with practical value are defendd vaccine, and are had special specific aim therapeutical effect at viral infection; And it can directly be virus antigen and pass antigen presentation APC cell Monocytes, excites the immunne response mechanism of lymphocytic immunity system, shortens the immune defence protection mechanism and induces the provocative reaction time.And anti-SARS clinical treatment medical science is verified, use SARS sufferer rehabilitation clients's serum antibody and can effectively treat the SARS patient with severe symptoms really, it confirms: in the molecular biosciences structural material of SARS virus, have can infected person's body induce inspire effective anti-SARS virus infect mechanism of causing a disease, some plants the protection antigen of humoral immunization protection responsing reaction mechanism, can make SARS virus the infected lymphocytic immunity system produce some kind blocking-up SARS virus that can effectively neutralize and infect the antibody of mechanism of causing a disease; It is the protection antigen that modern scientific research can utilize SARS virus from now on, and the SARS vaccine that research, design, exploitation, the manufacturing have practical value provides epochmaking definite clinical treatment medical science foundation.Therefore, with the antigenic specific antibody of SARS virus as biological adjuvant, it can directly be virus antigen passs antigen presentation APC cell Monocytes, excite the immunne response mechanism of lymphocytic immunity system, shorten the immune defence protection mechanism and induce the provocative reaction time, improve that reactionless or low reaction crowd excites immune response at inducing of SARS vaccine at the ARS vaccine; With the antigenic specific antibody of SARS virus as can effectively blocking the biological medicine that SARS virus infects mechanism of causing a disease; it can for or low reaction crowd reactionless at the ARS vaccine, with asymptomatic SARS virus the infected; effective anti-SARS virus infection immunity defence protection is provided, and has the special specific aim therapeutical effect that anti-SARS virus infects.Therefore SARS virus antigen and specific antibody is combined, can improve the actual use value of combination vaccine that SARS virus inactivated vaccine and subunit antigen protein vaccine and specific antibody constitute.For example, can obtain SARS totivirus inactivation antigen through results virus, freeze thawing, ultrasonic Treatment, filtration, purification, formalin-inactivated method by using Vero cell culture SARS virus, with the serum that obtains from SARS convalescent through centrifugal extraction gamma immune globulin, again through DE52 ion-exchange chromatography purification obtain, the specific polyclonal IgG antibody of SARS totivirus combines, and constitutes SARS totivirus inactivation antigen and specific polyclonal IgG antibody combination vaccine.For example; can be by the proteic expressing gene of subunit protection antigen S with SARS virus; the clone is transplanted on the saccharomycetic chromosome by modern genetic engineering; the subunit protection antigen S albumen of the SARS virus that expression is produced; with the serum that obtains by SARS virus subunit protection antigen S albumen in immune volunteer's health; through centrifugal extraction gamma immune globulin; obtain through DE52 ion-exchange chromatography purification again; the proteic specific polyclonal IgG of SARS virus subunit protection antigen S antibody combines, and constitutes SARS virus gene engineered subunit S proteantigen and specific polyclonal IgG antibody combination vaccine.For example, can be by the subunit antigen N albumen of above-mentioned modern genetic engineering method with SARS virus, subunit antigen M albumen, subunit 3CL antigen protein, or the gene clone of the proteic part fragment of SARS virus subunit antigen polypeptide expression is transplanted on the saccharomycetic chromosome, the SARS virus subunit antigen N albumen that expression is produced, subunit antigen M albumen, subunit 3CL antigen protein, or the proteic part fragment of SARS virus subunit antigen polypeptide, with corresponding human blood source specific polyclonal antibody, corresponding human blood source monoclonal antibody specific, corresponding biological engineering people source specific polyclonal antibody, corresponding biological engineering people source monoclonal antibody specific, corresponding biological engineering phage people source monoclonal antibody specific combines, and constitutes the various subunit protein antigens and the specific antibody combination vaccine of SARS virus.For example, can SARS totivirus antigen be decomposed into multiple different subunit antigen albumen by biochemical method, and the subunit antigen S albumen that obtains, subunit antigen M albumen, subunit antigen N albumen, subunit antigen 3CL albumen, or the proteic part fragment of SARS virus subunit antigen polypeptide, with corresponding human blood source specific polyclonal antibody, corresponding human blood source monoclonal antibody specific, corresponding biological engineering people source specific polyclonal antibody, corresponding biological engineering people source monoclonal antibody specific, corresponding biological engineering phage people source monoclonal antibody specific combines, and constitutes the various subunit protein antigens and the specific antibody combination vaccine of SARS virus.
The specific embodiment
For achieving the above object; implement the scheme that the present invention adopts: with (1) the .SARS totivirus inactivation antigen that is obtained; fully mix formation with the human blood source specific polyclonal antibody of (2) .5～30 times of weight; virus antigen directly can be and pass antigen presentation APC cell Monocytes; excite the immunne response mechanism of lymphocytic immunity system; shorten the immune defence protection mechanism and induce the provocative reaction time; improvement is reactionless at the SARS vaccine; the low reaction crowd excites immune response, the combination vaccine of SARS totivirus inactivation antigen and specific antibody at inducing of SARS vaccine.Be applied to prevent the urgent emergent prophylactic immunization of the new epidemic situation of SARS that may take place once more in the whole world, adult once inoculation is contained the SARS totivirus inactivation antigen of 5ug～100ug, the combination vaccine of this type of SARS totivirus inactivation antigen and specific antibody, repeated inoculation 1 time again after 2～4 weeks.
Implement the scheme that the present invention adopts: with the SARS totivirus inactivation antigen of (1) .5ug～50ug of being obtained; fully mix formation with (2) .1g human blood source specific polyclonal antibody; virus antigen directly can be and pass antigen presentation APC cell Monocytes; excite the immunne response mechanism of lymphocytic immunity system; shorten the immune defence protection mechanism and induce the provocative reaction time; improvement is reactionless at the SARS vaccine; the low reaction crowd excites immune response at inducing of SARS vaccine; can be for reactionless at the SARS vaccine; low immunoreation crowd; with asymptomatic SARS virus the infected; effective anti-SARS virus infection immunity defence protection is provided; and have a special specific aim therapeutical effect that anti-SARS virus infects, the combination vaccine of SARS totivirus inactivation antigen and specific antibody.Be applied to prevent the urgent emergent prophylactic immunization of the new epidemic situation of SARS that may take place once more in the whole world, the adult once inoculates the combination vaccine of this type of SARS totivirus inactivation antigen of 1g～2g and specific antibody, repeated inoculation 1 time again after 1 month.
Implement the scheme that the present invention adopts: with (1) the .SARS totivirus inactivation antigen that is obtained; fully mix formation with the biological engineering people source monoclonal antibody specific of (2) .1～5 times of weight; virus antigen directly can be and pass antigen presentation APC cell Monocytes; excite the immunne response mechanism of lymphocytic immunity system; shorten the immune defence protection mechanism and induce the provocative reaction time; improvement is reactionless at the SARS vaccine; the low reaction crowd excites immune response, the combination vaccine of SARS totivirus inactivation antigen and specific antibody at inducing of SARS vaccine.Be applied to prevent the urgent emergent prophylactic immunization of the new epidemic situation of SARS that may take place once more in the whole world, adult once inoculation is contained the SARS totivirus inactivation antigen of 5ug～100ug, the combination vaccine of this type of SARS totivirus inactivation antigen and specific antibody, repeated inoculation 1 time again after 2～4 weeks.
Implement the scheme that the present invention adopts: with the SARS totivirus inactivation antigen of (1) .20ug～100ug of being obtained; fully mix formation with (2) .1g biological engineering people source monoclonal antibody specific; virus antigen directly can be and pass antigen presentation APC cell Monocytes; excite the immunne response mechanism of lymphocytic immunity system; shorten the immune defence protection mechanism and induce the provocative reaction time; improvement is reactionless at the SARS vaccine; the low reaction crowd excites immune response at inducing of SARS vaccine; can be for reactionless at the SARS vaccine; low immunoreation crowd; with asymptomatic SARS virus the infected; effective anti-SARS virus infection immunity defence protection is provided; and have a special specific aim therapeutical effect that anti-SARS virus infects, the combination vaccine of SARS totivirus inactivation antigen and specific antibody.Be applied to prevent the urgent emergent prophylactic immunization of the new epidemic situation of SARS that may take place once more in the whole world, the adult once inoculates the combination vaccine of this type of SARS totivirus inactivation antigen of 0.2g～1g and specific antibody, repeated inoculation 1 time again after 1 month.
Implement the scheme that the present invention adopts: with (1) the .SARS viral sub-units antigen S albumen that is obtained; fully mix formation with the human blood source specific polyclonal antibody of (2) .5～30 times of weight; virus antigen directly can be and pass antigen presentation APC cell Monocytes; excite the immunne response mechanism of lymphocytic immunity system; shorten the immune defence protection mechanism and induce the provocative reaction time; improvement is reactionless at the SARS vaccine; the low reaction crowd excites immune response, the combination vaccine of SARS totivirus inactivation antigen and specific antibody at inducing of SARS vaccine.Be applied to prevent the urgent emergent prophylactic immunization of the new epidemic situation of SARS that may take place once more in the whole world, adult once inoculation is contained the SARS totivirus inactivation antigen of 5ug～100ug, the combination vaccine of this type of SARS virus subunit antigen S albumen and specific antibody, repeated inoculation 1 time again after 2～4 weeks.
Implement the scheme that the present invention adopts: with the SARS virus subunit antigen S albumen of (1) .5ug～50ug of being obtained; fully mix formation with (2) .1g human blood source specific polyclonal antibody; virus antigen directly can be and pass antigen presentation APC cell Monocytes; excite the immunne response mechanism of lymphocytic immunity system; shorten the immune defence protection mechanism and induce the provocative reaction time; improvement is reactionless at the SARS vaccine; the low reaction crowd excites immune response at inducing of SARS vaccine; can be for reactionless at the SARS vaccine; low immunoreation crowd; with asymptomatic SARS virus the infected; effective anti-SARS virus infection immunity defence protection is provided; and have a special specific aim therapeutical effect that anti-SARS virus infects, the combination vaccine of SARS totivirus inactivation antigen and specific antibody.Be applied to prevent the urgent emergent prophylactic immunization of the new epidemic situation of SARS that may take place once more in the whole world, the adult once inoculates the combination vaccine of this type of SARS virus subunit antigen S albumen of 1g～2g and specific antibody, repeated inoculation 1 time again after 1 month.
Implement the scheme that the present invention adopts: with (1) the .SARS viral sub-units antigen S albumen that is obtained; fully mix formation with the biological engineering people source monoclonal antibody specific of (2) .1～5 times of weight; virus antigen directly can be and pass antigen presentation APC cell Monocytes; excite the immunne response mechanism of lymphocytic immunity system; shorten the immune defence protection mechanism and induce the provocative reaction time; improvement is reactionless at the SARS vaccine; the low reaction crowd excites immune response, the combination vaccine of SARS virus subunit antigen S albumen and specific antibody at inducing of SARS vaccine.Be applied to prevent the urgent emergent prophylactic immunization of the new epidemic situation of SARS that may take place once more in the whole world, it is proteic that the adult once inoculates the SARS virus subunit antigen S that contains 5ug～100ug, the combination vaccine of this type of SARS totivirus inactivation antigen and specific antibody, repeated inoculation 1 time again after 2～4 weeks.
Implement the scheme that the present invention adopts: with the SARS virus subunit antigen S albumen of (1) .20ug～100ug of being obtained; fully mix formation with (2) .1g biological engineering people source monoclonal antibody specific; virus antigen directly can be and pass antigen presentation APC cell Monocytes; excite the immunne response mechanism of lymphocytic immunity system; shorten the immune defence protection mechanism and induce the provocative reaction time; improvement is reactionless at the SARS vaccine; the low reaction crowd excites immune response at inducing of SARS vaccine; can be for reactionless at the SARS vaccine; low immunoreation crowd; with asymptomatic SARS virus the infected; effective anti-SARS virus infection immunity defence protection is provided; and have a special specific aim therapeutical effect that anti-SARS virus infects, the combination vaccine of SARS virus subunit antigen S albumen and specific antibody.Be applied to prevent the urgent emergent prophylactic immunization of the new epidemic situation of SARS that may take place once more in the whole world, the adult once inoculates the combination vaccine of this type of SARS virus subunit antigen S albumen of 0.2g～1g and specific antibody, repeated inoculation 1 time again after 1 month.
The laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine.
For example, use hepatitis B virus surface antigen HBsAg albumen simulation SARS virus antigen S albumen, simulation SARS virus antigen M albumen, with mice anti-hbs monoclonal IgG antibody simulation specific antibody, the analog composite vaccine that constitutes is done, common laboratory animal mice, immunodeficiency laboratory animal nude mouse, simulated SARS virus subunit antigen albumen separately respectively, simulation SARS virus subunit antigen albumen and the analog composite vaccine of simulating specific antibody, can induce the simulation contrast preliminary experiment that inspires different immune responses: uses 30 6～8 all ages male BALB/c mouse, 30 6～8 the week age male BALB/c-nu/nu immunodeficiency nude mouse, be divided into 1 separately, 2,3 groups, every group each 10 numbering experiment mices; Get 5mg hepatitis B virus surface antigen HBsAg albumen, with 5mg mice anti-hbs monoclonal IgG antibody, put under the aseptic mortar room temperature light through grinding the analog composite vaccine that fully mixed, is prepared into hepatitis B virus surface antigen HBsAg albumen and monoclonal IgG antibody in 5 minutes, other gets 5mg hepatitis B virus surface antigen HBsAg albumen, and other gets 5mg mice anti-hbs monoclonal IgG antibody; Respectively 0,7,14 days, give 1 group 10 numbering experiments BALB/c mouse is subcutaneous and inject 3ug's separately, antigen HBsAg protein 10 0ul normal saline solution, give 2 groups 10 numbering experiments BALB/c mouse is subcutaneous and inject 3ug's separately, mice anti-hbs monoclonal IgG antibody 100ul normal saline solution, give 3 groups 10 numbering experiments BALB/c mouse is subcutaneous and inject 6ug's separately, the analog composite vaccine of antigen HBsAg albumen and monoclonal IgG antibody, give that 1 group 10 numbering experiment BALB/c-nu/nu immunodeficiency nude mouses are subcutaneous injects 3ug's separately, antigen HBsAg protein 10 0ul normal saline solution, give that 2 groups 10 numbering experiment BALB/c-nu/nu immunodeficiency nude mouses are subcutaneous injects 3ug's separately, mice anti-hbs monoclonal IgG antibody 100ul normal saline solution gives that 3 groups 10 numbering experiment BALB/c-nu/nu immunodeficiency nude mouses are subcutaneous injects 6ug's separately, the analog composite vaccine 100ul normal saline solution of antigen HBsAg albumen and monoclonal IgG antibody; Respectively at the 10th, 15,20,30,40 day, to all BALB/c numbering mices, the blood sampling of BALB/c-nu/nu numbering immunodeficiency nude mouse afterbody, use the ELISA method and detect respectively and number experiment mice separately and induced and excite expressed anti-HBsAg antibody IgM of humoral immunoresponse(HI) reaction and concentration and the pests occurrence rule of IgG, induced the concentration and the pests occurrence rule that excite the anti-HBsAg IgG antibody 2 cytotoxic by complement-mediated, that the cellullar immunologic response reaction is expressed.Relative analysis simulation preliminary experiment application simulation specific antibody is as biological adjuvant; to common laboratory animal mice, immunodeficiency laboratory animal nude mouse, can strengthen simulation SARS candidate vaccine immunogenicity, with shorten the immune defence protection mechanism and induce the biological adjuvant effect of provocative reaction time.Will be at the analog composite vaccine of the 3rd group of injections of antigens HBsAg albumen and monoclonal IgG antibody; the detected anti-HBsAg antibody concentration of laboratory animal; deduct at the 2nd group and only inject monoclonal IgG antibody; the detected anti-HBsAg antibody concentration of laboratory animal; with only injections of antigens HBsAg is proteic at the 1st group; the detected anti-HBsAg antibody concentration of laboratory animal is made comparisons; can acquire the simulation specific antibody as biological adjuvant; to common laboratory animal mice; immunodeficiency laboratory animal nude mouse can strengthen the immunogenicity of simulating the SARS candidate vaccine; with shorten the immune defence protection mechanism and induce the biological adjuvant effect of provocative reaction time.It can be for the combination vaccine of following SARS virus antigen S albumen, SARS virus antigen M albumen and the specific antibody that will do, and the laboratory animal mice is induced to excite the immune response contrast experiment, accumulation test experience.
For example, the combination vaccine of inferior former S albumen of monoclonal antibody of application SARS virus and specific antibody is done, common laboratory animal mice, immunodeficiency laboratory animal nude mouse, separately respectively by the combination vaccine of SARS virus subunit antigen S albumen, SARS virus subunit antigen S albumen and specific antibody, can induce the contrast experiment who inspires different immune responses: use 30 6～8 age in week male BALB/c mouse, 30 6～8 age in week male BALB/c-nu/nu immunodeficiency nude mouse, be divided into 1,2,3 group separately, every group each 10 numbering experiment mices; Get the SARS virus subunit antigen S albumen of 5mg, with 10mg from tens by the former S albumen of the inferior monoclonal antibody of the SARS virus BALB/c mouse heart extracting blood crossed of immunity repeatedly, the serum that obtains is through centrifugal extraction gamma immune globulin, obtain through DE52 ion-exchange chromatography purification again, the proteic specific polyclonal IgG of SARS virus subunit protection antigen S antibody, put under the aseptic mortar room temperature and gently fully mix through grinding 5 minutes, be prepared into the combination vaccine of SARS virus subunit antigen S albumen and specific polyclonal IgG antibody, other gets the SARS virus subunit antigen S albumen of 5mg, and other gets the proteic specific polyclonal IgG of the SARS virus subunit antigen S antibody of 10mg; Respectively 0,7,14 days, give 1 group 10 numbering experiments BALB/c mouse is subcutaneous and inject 3ug's separately, SARS virus subunit antigen S protein 10 0ul normal saline solution, give 2 groups 10 numbering experiments BALB/c mouse is subcutaneous and inject 6ug's separately, the proteic specific polyclonal IgG of SARS virus subunit antigen S antibody 100ul normal saline solution, give 3 groups 10 numbering experiments BALB/c mouse is subcutaneous and inject 9ug's separately, the combination vaccine 100ul normal saline solution of SARS virus subunit antigen S albumen and specific polyclonal IgG antibody, give that 1 group 10 numbering experiment BALB/c-nu/nu immunodeficiency nude mouses are subcutaneous injects 3ug's separately, SARS virus subunit antigen S protein 10 0ul normal saline solution, give that 2 groups 10 numbering experiment BALB/c-nu/nu immunodeficiency nude mouses are subcutaneous injects 6ug's separately, the proteic specific polyclonal IgG of SARS virus subunit antigen S antibody 100ul normal saline solution gives that 3 groups 10 numbering experiment BALB/c-nu/nu immunodeficiency nude mouses are subcutaneous injects 9ug's separately, the combination vaccine 100ul normal saline solution of SARS virus subunit antigen S albumen and specific polyclonal IgG antibody; Respectively at the 10th, 15,20,30,40 day, to all BALB/c numbering mices, the blood sampling of BALB/c-nu/nu numbering immunodeficiency nude mouse afterbody, application ELISA method detects respectively numbers experiment mice separately, induced to excite humoral immunoresponse(HI) reaction concentration and pests occurrence rule expressed, anti-SARS virus subunit antigen S protein antibodies IgM and IgG, induced the concentration and the pests occurrence rule that excite the anti-SARS virus subunit antigen S protein antibodies IgG2 cytotoxic by complement-mediated, that the cellullar immunologic response reaction is expressed.The proteic specific polyclonal IgG of relative analysis experimental applications SARS virus subunit antigen S antibody is as biological adjuvant; to common laboratory animal mice, immunodeficiency laboratory animal nude mouse, immunogenicity that can enhanced SAR S candidate vaccine, with shorten the immune defence protection mechanism and induce the biological adjuvant effect of provocative reaction time.Will be at the combination vaccine of the 3rd group of injection SARS virus subunit antigen S albumen and specific polyclonal IgG antibody; the detected anti-SARS virus subunit antigen of laboratory animal S protein antibodies concentration; deduct at the 2nd group and only inject the proteic specific polyclonal IgG of SARS virus subunit antigen S antibody; the detected anti-SARS virus subunit antigen of laboratory animal S protein antibodies concentration; with only injections of antigens SARS virus subunit antigen S is proteic at the 1st group; the detected anti-SARS virus subunit antigen of laboratory animal S protein antibodies concentration is made comparisons; can acquire the proteic specific antibody of SARS virus subunit antigen S as biological adjuvant; to common laboratory animal mice; immunodeficiency laboratory animal nude mouse, immunogenicity that can enhanced SAR S candidate vaccine; with shorten the immune defence protection mechanism and induce the biological adjuvant effect of provocative reaction time.
For example, the combination vaccine of inferior former M albumen of monoclonal antibody of application SARS virus and specific antibody is done, common laboratory animal mice, immunodeficiency laboratory animal nude mouse, separately respectively by the combination vaccine of SARS virus subunit antigen M albumen, SARS virus subunit antigen M albumen and specific antibody, can induce the contrast experiment who inspires different immune responses: use 30 6～8 age in week male BALB/c mouse, 30 6～8 age in week male BALB/c-nu/nu immunodeficiency nude mouse, be divided into 1,2,3 group separately, every group each 10 numbering experiment mices; Get the SARS virus subunit antigen M albumen of 5mg, with 10mg from tens by the former M albumen of the inferior monoclonal antibody of the SARS virus BALB/c mouse heart extracting blood crossed of immunity repeatedly, the serum that obtains is through centrifugal extraction gamma immune globulin, obtain through DE52 ion-exchange chromatography purification again, the proteic specific polyclonal IgG of SARS virus subunit protection antigen M antibody, put under the aseptic mortar room temperature and gently fully mix through grinding 5 minutes, be prepared into the combination vaccine of SARS virus subunit antigen M albumen and specific polyclonal IgG antibody, other gets the SARS virus subunit antigen M albumen of 5mg, and other gets the proteic specific polyclonal IgG of the SARS virus subunit antigen M antibody of 10mg; Respectively 0,7,14 days, give 1 group 10 numbering experiments BALB/c mouse is subcutaneous and inject 3ug's separately, SARS virus subunit antigen M protein 10 0ul normal saline solution, give 2 groups 10 numbering experiments BALB/c mouse is subcutaneous and inject 6ug's separately, the proteic specific polyclonal IgG of SARS virus subunit antigen M antibody 100ul normal saline solution, give 3 groups 10 numbering experiments BALB/c mouse is subcutaneous and inject 9ug's separately, the combination vaccine 100ul normal saline solution of SARS virus subunit antigen M albumen and specific polyclonal IgG antibody, give that 1 group 10 numbering experiment BALB/c-nu/nu immunodeficiency nude mouses are subcutaneous injects 3ug's separately, SARS virus subunit antigen M protein 10 0ul normal saline solution, give that 2 groups 10 numbering experiment BALB/c-nu/nu immunodeficiency nude mouses are subcutaneous injects 6ug's separately, the proteic specific polyclonal IgG of SARS virus subunit antigen M antibody 100ul normal saline solution gives that 3 groups 10 numbering experiment BALB/c-nu/nu immunodeficiency nude mouses are subcutaneous injects 9ug's separately, the combination vaccine 100ul normal saline solution of SARS virus subunit antigen M albumen and specific polyclonal IgG antibody; Respectively at the 10th, 15,20,30,40 day, to all BALB/c numbering mices, the blood sampling of BALB/c-nu/nu numbering immunodeficiency nude mouse afterbody, application ELISA method detects respectively numbers experiment mice separately, induced to excite humoral immunoresponse(HI) reaction concentration and pests occurrence rule expressed, anti-SARS virus subunit antigen M protein antibodies IgM and IgG, induced to excite, cellullar immunologic response reaction concentration and pests occurrence rule expressed, anti-SARS virus subunit antigen M protein antibodies IgG2 cytotoxic by complement-mediated.The proteic specific polyclonal IgG of relative analysis experimental applications SARS virus subunit antigen M antibody is as biological adjuvant; to common laboratory animal mice, immunodeficiency laboratory animal nude mouse, immunogenicity that can enhanced SAR S candidate vaccine, with shorten the immune defence protection mechanism and induce the biological adjuvant effect of provocative reaction time.Will be at the combination vaccine of the 3rd group of injection SARS virus subunit antigen M albumen and specific polyclonal IgG antibody; the detected anti-SARS virus subunit antigen of laboratory animal M protein antibodies concentration; deduct at the 2nd group and only inject the proteic specific polyclonal IgG of SARS virus subunit antigen M antibody; the detected anti-SARS virus subunit antigen of laboratory animal M protein antibodies concentration; with only injections of antigens SARS virus subunit antigen M is proteic at the 1st group; the detected anti-SARS virus subunit antigen of laboratory animal M protein antibodies concentration is made comparisons; can acquire the proteic specific antibody of SARS virus subunit antigen M as biological adjuvant; to common laboratory animal mice; immunodeficiency laboratory animal nude mouse, immunogenicity that can enhanced SAR S candidate vaccine; with shorten the immune defence protection mechanism and induce the biological adjuvant effect of provocative reaction time.
Claims (15)
1. SARS virus antigen-antibody combination vaccine, it is characterized in that: it is by SARS virus antigen (1), with the compound formation of the antigenic specific antibody of SARS virus (2).
2. the laboratory animal immunne response contrast experiment model and method of a SARS virus antigen-antibody combination vaccine, it is characterized in that: it is divided into groups by common laboratory animal (3), inject SARS virus antigen (1) respectively, SARS virus antigen-antibody combination vaccine, blood sampling detects and to number laboratory animal separately and induced and excite the humoral immunoresponse(HI) reaction expressed respectively, antigenic antibody concentration of anti-SARS virus and pests occurrence rule, by induced excite by complement-mediated cytotoxic, the cellullar immunologic response reaction is expressed, antigenic antibody concentration of anti-SARS virus and pests occurrence rule, the antigenic specific antibody of relative analysis experimental applications SARS virus (2) can change the biological adjuvant effect of laboratory animal at SARS virus candidate vaccine immunne response mechanism as biological adjuvant.
3. the laboratory animal immunne response contrast experiment's model and the experimental technique of a SARS virus antigen-antibody combination vaccine, it is characterized in that: it is by common laboratory animal (3), immunodeficiency laboratory animal (4) grouping, inject SARS virus antigen (1) respectively, SARS virus antigen-antibody combination vaccine, blood sampling detects and to number laboratory animal separately and induced and excite the humoral immunoresponse(HI) reaction expressed respectively, antigenic antibody concentration of anti-SARS virus and pests occurrence rule, by induced excite by complement-mediated cytotoxic, the cellullar immunologic response reaction is expressed, antigenic antibody concentration of anti-SARS virus and pests occurrence rule, the antigenic specific antibody of relative analysis experimental applications SARS virus (2) can change common laboratory animal as biological adjuvant, the immunodeficiency laboratory animal is at the biological adjuvant effect of SARS virus candidate vaccine immunne response mechanism.
4. according to the SARS virus antigen-antibody combination vaccine described in the claim 1 to 3, and the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine, it is characterized in that: SARS virus antigen (1) is SARS totivirus inactivation antigen.
5. according to the SARS virus antigen-antibody combination vaccine described in the claim 1 to 3, and the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine, it is characterized in that: SARS virus antigen (1) is SARS virus subunit antigen albumen.
6. according to the SARS virus antigen-antibody combination vaccine described in the claim 1 to 3, and the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine, it is characterized in that: SARS virus antigen (1) is SARS virus subunit antigen S albumen.
7. according to the SARS virus antigen-antibody combination vaccine described in the claim 1 to 3, and the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine, it is characterized in that: SARS virus antigen (1) is SARS virus subunit antigen M albumen.
8. according to the SARS virus antigen-antibody combination vaccine described in the claim 1 to 7, and the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine, it is characterized in that: SARS virus antigen (1) is the proteic part fragment of SARS virus subunit antigen polypeptide.
9. according to the SARS virus antigen-antibody combination vaccine described in the claim 1 to 8, and the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine, it is characterized in that: the antigenic specific antibody of SARS virus (2) is a human blood source polyclone specific antibody.
10. according to the SARS virus antigen-antibody combination vaccine described in the claim 1 to 8, and the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine, it is characterized in that: the antigenic specific antibody of SARS virus (2) is a human blood resource monoclonal specific antibody.
11. according to the SARS virus antigen-antibody combination vaccine described in the claim 1 to 8, and the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine, it is characterized in that: the antigenic specific antibody of SARS virus (2) is a biological engineering people source polyclone specific antibody.
12. according to the SARS virus antigen-antibody combination vaccine described in the claim 1 to 8, and the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine, it is characterized in that: the antigenic specific antibody of SARS virus (2) is a biological engineering people resource monoclonal specific antibody.
13. according to the SARS virus antigen-antibody combination vaccine described in the claim 1 to 8, and the laboratory animal immunne response contrast experiment's model and the experimental technique of SARS virus antigen-antibody combination vaccine, it is characterized in that: the antigenic specific antibody of SARS virus (2) is a biological engineering phage people resource monoclonal specific antibody.
14. laboratory animal immunne response contrast experiment's model and experimental technique according to the SARS virus antigen-antibody combination vaccine described in the claim 2,3 is characterized in that: common laboratory animal (3) is the laboratory animal mice.
15. laboratory animal immunne response contrast experiment's model and experimental technique according to the SARS virus antigen-antibody combination vaccine described in the claim 3, it is characterized in that: common laboratory animal (3) is the laboratory animal mice, and immunodeficiency laboratory animal (4) is the laboratory animal nude mouse.
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| CNA031462316A Pending CN1480215A (en) | 2003-07-07 | 2003-07-07 | Compound antibody vaccine of SARS virus antigen as well as its model of experimental animal and method |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019509350A (en) * | 2016-03-21 | 2019-04-04 | ビー．ウェイナー デイビッド | DNA antibody construct and method of use thereof |
| CN111840532A (en) * | 2020-08-03 | 2020-10-30 | 陈继明 | Live vaccine for preventing viral infectious diseases |
| CN112933221A (en) * | 2021-02-22 | 2021-06-11 | 陈继明 | Immune complex vaccine |
| CN112972669A (en) * | 2021-03-08 | 2021-06-18 | 河南道特尔医药科技股份有限公司 | Animal experiment operation method for improving secretion of antibody of new corona vaccine to special population |
| US11208470B2 (en) | 2012-12-13 | 2021-12-28 | The Trustees Of The University Of Pennsylvania | DNA antibody constructs and method of using same |
| US11278619B2 (en) | 2014-12-01 | 2022-03-22 | The Trustees Of The University Of Pennsylvania | DNA antibody constructs and method of using same |
-
2003
- 2003-07-07 CN CNA031462316A patent/CN1480215A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US11208470B2 (en) | 2012-12-13 | 2021-12-28 | The Trustees Of The University Of Pennsylvania | DNA antibody constructs and method of using same |
| US11278619B2 (en) | 2014-12-01 | 2022-03-22 | The Trustees Of The University Of Pennsylvania | DNA antibody constructs and method of using same |
| JP2019509350A (en) * | 2016-03-21 | 2019-04-04 | ビー．ウェイナー デイビッド | DNA antibody construct and method of use thereof |
| EP3432918A4 (en) * | 2016-03-21 | 2020-02-12 | David B. Weiner | Dna antibody constructs and method of using same |
| CN111840532A (en) * | 2020-08-03 | 2020-10-30 | 陈继明 | Live vaccine for preventing viral infectious diseases |
| CN112933221A (en) * | 2021-02-22 | 2021-06-11 | 陈继明 | Immune complex vaccine |
| CN112972669A (en) * | 2021-03-08 | 2021-06-18 | 河南道特尔医药科技股份有限公司 | Animal experiment operation method for improving secretion of antibody of new corona vaccine to special population |
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