Vaxfectin enhances the humoral immune response to plasmid DNA-encoded antigens

被引:79
|
作者
Hartikka, J
Bozoukova, V
Ferrari, M
Sukhu, L
Enas, J
Sawdey, M
Wloch, MK
Tonsky, K
Norman, J
Manthorpe, M
Wheeler, CJ
机构
[1] Vical Inc, Dept Chem, San Diego, CA 92121 USA
[2] Vical Inc, Dept Cell Biol, San Diego, CA 92121 USA
[3] Vical Inc, Dept Pharmacol, San Diego, CA 92121 USA
关键词
genetic immunization; plasmid DNA; cationic lipid;
D O I
10.1016/S0264-410X(00)00445-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
This report characterizes Vaxfectin, a novel cationic and neutral lipid formulation which enhances antibody responses when complexed with an antigen-encoding plasmid DNA (pDNA). In mice, intramuscular injection of Vaxfectin formulated with pDNA encoding influenza nucleoprotein (NP) increased antibody titers up to 20-fold. to levels that could not be reached with pDNA alone. As little as 1 mug of pDNA formulated with Vaxfectin per muscle resulted in higher anti-NP titers than that obtained with 25 mug naked pDNA. The antibody titers in animals injected with Vaxfectin-pDNA remained higher than in the naked pDNA controls for at least 9 months. The enhancement in antibody titers was dependent on the Vaxfectin dose and was accomplished without diminishing the strong anti-NP cytolytic T cell response typical of pDNA-based vaccines. In rabbits, complexing pDNA with Vaxfectin enhanced antibody titers up to 50 fold with needle and syringe injections and also augmented humoral responses when combined with a needle-free injection device. Vaxfectin did not facilitate transfection and/or increase synthesis of beta -galactosidase reporter protein in muscle tissue. ELISPOT assays performed on bone marrow cells from vaccinated mice showed that Vaxfectin produced a three- to five-fold increase in the number of NP-specific plasma cells. Thus. Vaxfectin should be a useful adjuvant for enhancing pDNA-based vaccinations. (C) 7001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1911 / 1923
页数:13
相关论文
共 50 条
  • [1] IMMUNE-RESPONSE TO PLASMID-ENCODED AND CHROMOSOME-ENCODED YERSINIA ANTIGENS
    MAZZA, G
    KARU, AE
    KINGSBURY, DT
    INFECTION AND IMMUNITY, 1985, 48 (03) : 676 - 685
  • [2] Unraveling a Multifactorial Host Immune Response to Intramuscular Electrotransfer of DNA-Encoded Antibody Therapy
    Thomas, Debby
    Sprooten, Jenny
    Govaerts, Jannes
    Merchiers, Pascal
    Dewilde, Maarten
    Garg, Abhishek
    Hollevoet, Kevin
    Geukens, Nick
    MOLECULAR THERAPY, 2024, 32 (04) : 233 - 234
  • [3] Vaxfectin enhances antigen specific antibody titers and maintains Th1 type immune responses to plasmid DNA immunization
    Reyes, L
    Hartikka, J
    Bozoukova, V
    Sukhu, L
    Nishioka, W
    Singh, G
    Ferrari, M
    Enas, J
    Wheeler, CJ
    Manthorpe, M
    Wloch, MK
    VACCINE, 2001, 19 (27) : 3778 - 3786
  • [4] Vaxfectin™ enhances immunization with very low doses of plasmid DNA in a mouse malaria vaccine model
    Sedegah, Martha
    Rogers, William O.
    Belmonte, Arnel
    Belmonte, Maria
    Banania, Glenna
    Patterson, Noelle
    Ferrari, Marilyn
    Kaslow, David
    Richie, Thomas L.
    Doolan, Denise L.
    AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2005, 73 (06): : 292 - 292
  • [5] Bacterial ghosts as carriers of protein subunit and DNA-encoded antigens for vaccine applications
    Muhammad, Abbas
    Champeimont, Jonathan
    Mayr, Ulrike Beate
    Lubitz, Werner
    Kudela, Pavol
    EXPERT REVIEW OF VACCINES, 2012, 11 (01) : 97 - 116
  • [6] Evaluation of the humoral immune response to Strongyloides venezuelensis antigens
    Rigo, Carla Rodrigues
    Lescano, Susana Zevallos
    de Marchi, Claudia Regina
    Amato Neto, Vicente
    REVISTA DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL, 2008, 41 (06) : 648 - 653
  • [7] HUMORAL IMMUNE-RESPONSE TO FILARIAL ANTIGENS IN CHYLURIA
    RAJA, A
    HUSSAIN, R
    PRABHAKAR, R
    NARAYANAN, PR
    JOURNAL OF BIOSCIENCES, 1984, 6 (05) : 723 - 728
  • [8] The complexity of the humoral immune response against HLA antigens
    Schaub, Stefan
    Hoenger, Gideon
    Amico, Patrizia
    TRANSPLANT INTERNATIONAL, 2014, 27 (03) : 249 - 250
  • [9] SEROLOGICAL RESPONSE TO PLASMID-ENCODED ANTIGENS IN CHILDREN AND ADULTS WITH SHIGELLOSIS
    ECHEVERRIA, P
    HANCHALAY, S
    TAYLOR, DN
    DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 1988, 10 (02) : 75 - 80
  • [10] Coexpressed RIG-I Agonist Enhances Humoral Immune Response to Influenza DNA Vaccine
    Williams, James A.
    Luke, Jeremy
    Hodgson, Clague P.
    MOLECULAR THERAPY, 2009, 17 : S370 - S370