Intranasal interleukin-12 is a powerful adjuvant for protective mucosal immunity

被引:73
作者
Arulanandam, BP
O'Toole, M
Metzger, DW
机构
[1] Med Coll Ohio, Dept Microbiol & Immunol, Toledo, OH 43699 USA
[2] Genet Inst Inc, Cambridge, MA 02140 USA
来源
JOURNAL OF INFECTIOUS DISEASES | 1999年 / 180卷 / 04期
关键词
D O I
10.1086/314996
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The use of interleukin (IL)-12 as a new vaccine adjuvant for stimulating protective antiviral mucosal immunity has been examined, Mice were immunized intranasally (in) with an influenza vaccine consisting of soluble hemagglutinin (H1) and neuraminidase (N1) plus IL-12. This treatment resulted in elevated levels of lung and splenic interferon-gamma and IL-10 mRNA, Total and IgG2a anti-H1N1 antibody levels in serum were significantly elevated, as were total, IgG1, IgG2a, and secretory IgA antibody levels in bronchoalveolar lavage (BAL) fluids compared with animals receiving vaccine alone. Mice immunized in with vaccine and IL-12 also exhibited decreased weight loss and dramatically enhanced survival after lethal challenge with infectious influenza virus. Protection was dependent upon the presence of B cells and could be transferred to naive mice by inoculation of either serum or BAL fluid from IL-12-treated mice. These findings show for the first time that soluble IL-12 delivered in serves as a powerful respiratory adjuvant for protective antiviral immunity.
引用
收藏
页码:940 / 949
页数:10
相关论文
共 50 条
  • [21] GRAHAM BS, 1993, J IMMUNOL, V151, P2032
  • [22] Resistance to and recovery from lethal influenza virus infection in B lymphocyte-deficient mice
    Graham, MB
    Braciale, TJ
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (12) : 2063 - 2068
  • [23] Greenberger MJ, 1996, J IMMUNOL, V157, P3006
  • [24] A B-CELL-DEFICIENT MOUSE BY TARGETED DISRUPTION OF THE MEMBRANE EXON OF THE IMMUNOGLOBULIN MU-CHAIN GENE
    KITAMURA, D
    ROES, J
    KUHN, R
    RAJEWSKY, K
    [J]. NATURE, 1991, 350 (6317) : 423 - 426
  • [25] IDENTIFICATION AND PURIFICATION OF NATURAL-KILLER CELL STIMULATORY FACTOR (NKSF), A CYTOKINE WITH MULTIPLE BIOLOGIC EFFECTS ON HUMAN-LYMPHOCYTES
    KOBAYASHI, M
    FITZ, L
    RYAN, M
    HEWICK, RM
    CLARK, SC
    CHAN, S
    LOUDON, R
    SHERMAN, F
    PERUSSIA, B
    TRINCHIERI, G
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1989, 170 (03) : 827 - 845
  • [26] Interaction of antigens and antibodies at mucosal surfaces
    Lamm, ME
    [J]. ANNUAL REVIEW OF MICROBIOLOGY, 1997, 51 : 311 - 340
  • [27] Leonard JP, 1997, BLOOD, V90, P2541
  • [28] MACATONIA SE, 1995, J IMMUNOL, V154, P5071
  • [29] Oral but not parenteral interleukin (IL)-12 redirects T helper 2 (Th2)-type responses to an oral vaccine without altering mucosal IgA responses
    Marinaro, M
    Boyaka, PN
    Finkelman, FD
    Kiyono, H
    Jackson, RJ
    Jirillo, E
    McGhee, JR
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (03) : 415 - 427
  • [30] MCKNIGHT AJ, 1994, J IMMUNOL, V152, P2172