Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Acta Pathologica Microbiologica et Immunologica Scandinavica |
| Vol/bind | 106 |
| Udgave nummer | 6 |
| Sider (fra-til) | 636-46 |
| Antal sider | 10 |
| ISSN | 0903-4641 |
| Status | Udgivet - 1998 |
Bibliografisk note
Keywords: AIDS Vaccines; Amino Acid Sequence; Animals; Antibodies, Viral; Biolistics; Cytotoxicity, Immunologic; Female; HIV-1; Hepatitis B Vaccines; Hepatitis B virus; Immunization Schedule; Immunization, Secondary; Injections, Intramuscular; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Sequence Data; T-Lymphocytes, Cytotoxic; Transfection; Vaccines, DNACitationsformater
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Comparisons of DNA-mediated immunization procedures directed against surface glycoproteins of human immunodeficiency virus type-1 and hepatitis B virus. / Fomsgaard, A; Nielsen, H V; Nielsen, C; Johansson, K; Machuca, R; Bruun, L; Hansen, J; Buus, S.
I: Acta Pathologica Microbiologica et Immunologica Scandinavica, Bind 106, Nr. 6, 1998, s. 636-46.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Comparisons of DNA-mediated immunization procedures directed against surface glycoproteins of human immunodeficiency virus type-1 and hepatitis B virus
AU - Fomsgaard, A
AU - Nielsen, H V
AU - Nielsen, C
AU - Johansson, K
AU - Machuca, R
AU - Bruun, L
AU - Hansen, J
AU - Buus, S
N1 - Keywords: AIDS Vaccines; Amino Acid Sequence; Animals; Antibodies, Viral; Biolistics; Cytotoxicity, Immunologic; Female; HIV-1; Hepatitis B Vaccines; Hepatitis B virus; Immunization Schedule; Immunization, Secondary; Injections, Intramuscular; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Sequence Data; T-Lymphocytes, Cytotoxic; Transfection; Vaccines, DNA
PY - 1998
Y1 - 1998
N2 - DNA vaccination methods were compared to examine the in vivo expression of HIV-1 gp160 and beta-galactosidase, and the resulting immune response. Beta-galactosidase plasmid showed expression rates of 2-5% of muscle fibers with or without pretreatments using bupivacaine or cardiotoxin facilitators 1 or 5 days earlier, respectively. In contrast, HIV gp160 expression was lower in untreated or bupivacaine-treated muscles, but was improved by pretreatment with cardiotoxin. Equal expression of beta-galactosidase and HIV gp160 was obtained using gene gun delivery to the epidermis. Unlike the i.m. in situ expression of gp160, the anti-HIV antibody response did not improve after muscle pretreatments but depended on the vaccination intervals. Gene gun delivery of pMN160 also resulted in a slow and low titered antibody response. In contrast, a single i.m. injection of plasmid encoding another viral envelope, HBsAg, resulted in earlier seroconversion to high titers without the need for pretreatments or boostings. Intradermal inoculation by gene gun using 100-fold less DNA resulted in the same anti-HBsAg antibody profile only after boostings. In contrast to the differences in antibody responses, a specific CTL response was obtained in all cases. Bupivacaine-treated muscles showed an extreme degree of edema with disruption of connective tissue (endo- and mesomysium) and was not well tolerated (4 of 19 mice died). Cardiotoxin created muscle necrosis and occasional (2 of 20 mice) development of fibrotic muscles. It is concluded that in vivo expression cannot be properly predicted using reporter gene experiments and that the resulting immune response does not follow directly with the expression rate. It is suggested that the antibody response may depend primarily on the nature of the antigen expressed rather than the DNA vaccination method. It is proposed that gene gun or i.m. injection be used without pretreatment in the case of DNA vaccination with plasmid encoding HIV MN gp160.
AB - DNA vaccination methods were compared to examine the in vivo expression of HIV-1 gp160 and beta-galactosidase, and the resulting immune response. Beta-galactosidase plasmid showed expression rates of 2-5% of muscle fibers with or without pretreatments using bupivacaine or cardiotoxin facilitators 1 or 5 days earlier, respectively. In contrast, HIV gp160 expression was lower in untreated or bupivacaine-treated muscles, but was improved by pretreatment with cardiotoxin. Equal expression of beta-galactosidase and HIV gp160 was obtained using gene gun delivery to the epidermis. Unlike the i.m. in situ expression of gp160, the anti-HIV antibody response did not improve after muscle pretreatments but depended on the vaccination intervals. Gene gun delivery of pMN160 also resulted in a slow and low titered antibody response. In contrast, a single i.m. injection of plasmid encoding another viral envelope, HBsAg, resulted in earlier seroconversion to high titers without the need for pretreatments or boostings. Intradermal inoculation by gene gun using 100-fold less DNA resulted in the same anti-HBsAg antibody profile only after boostings. In contrast to the differences in antibody responses, a specific CTL response was obtained in all cases. Bupivacaine-treated muscles showed an extreme degree of edema with disruption of connective tissue (endo- and mesomysium) and was not well tolerated (4 of 19 mice died). Cardiotoxin created muscle necrosis and occasional (2 of 20 mice) development of fibrotic muscles. It is concluded that in vivo expression cannot be properly predicted using reporter gene experiments and that the resulting immune response does not follow directly with the expression rate. It is suggested that the antibody response may depend primarily on the nature of the antigen expressed rather than the DNA vaccination method. It is proposed that gene gun or i.m. injection be used without pretreatment in the case of DNA vaccination with plasmid encoding HIV MN gp160.
M3 - Journal article
C2 - 9725796
VL - 106
SP - 636
EP - 646
JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
SN - 0903-4641
IS - 6
ER -