Thanks, russet. Good stuff, and I'm glad to know that someone has moved it up to three antigens.
The HSV vector..... it's still gonna be immunogenic. Same old problems.
I was wondering if one could do a "whole body gene gun" injection thingie, after taking steps to activate DCs.......
Immunology 2002 Sep;107(1):69-76
The haemopoietic growth factor, Flt3L, alters the immune response induced by transcutaneous immunization.
Baca-Estrada ME, Ewen C, Mahony D, Babiuk LA, Wilkie D, Foldvari M.
Veterinary Infectious Disease Organization, Department of Animal and Poultry Science and College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Canada.
Topical application of antigen induces antigen-specific humoral and cellular immune responses. In this study we examined whether expansion of dendritic cells (DC) by Flt3 ligand (Flt3L) treatment influences the induction of immune responses following transcutaneous immunization. Mice were treated intraperitoneally with Flt3L or phosphate-buffered saline (PBS) and immunized transcutaneously with hen egg lysozyme (HEL). Flt3L-treated mice developed lower HEL-specific cellular and humoral immune responses than PBS-treated mice. However, in the presence of cholera toxin (CT), a potent adjuvant for mucosal and transcutaneous immunization, Flt3L-treated mice developed significantly higher cellular and humoral immune responses to HEL when compared to PBS-treated mice. We assessed whether the immunomodulatory effects of CT were a result of activation of epidermal dendritic cells (Langerhans' cells; LC). Our results indicate that within 8-12 hr of topical application of CT, epidermal LC cells lose their dendritic morphology and become rounder in appearance. In addition, we observed enhanced expression of major histocompatibility complex (MHC) class II, and of adhesion molecules CD11c and intracellular adhesion molecule-1 (ICAM-1). Our observations support the concept that the state of activation of DC in the skin is central to the regulation of immune responses. This information is relevant to the design of effective transcutaneous vaccination strategies.
AIDS Res Hum Retroviruses 2002 Jul 1;18(10):715-22
Epidermal powder immunization with a recombinant HIV gp120 targets Langerhans cells and induces enhanced immune responses.
Chen D, Zuleger C, Chu Q, Maa YF, Osorio J, Payne LG.
PowderJect Vaccines, Inc., 585 Science Drive, Madison, WI 53711, USA.
The recombinant envelope gp120 (rgp120) of human immunodeficiency virus (HIV) is a weak immunogen when administered by intramuscular (IM) injection. In the present study, we report that epidermal powder immunization (EPI) elicits robust antibody responses to the rgp120. EPI of mice with a dose 0.2-5 microg of rgp120 protein elicited geometric mean antibody titers that were 18- to 240-fold higher than that elicited by IM injection using a 5.0 microg dose. Targeting antigen to and mobilization of Langerhans cells (LCs) by EPI may explain the enhanced immunogenicity of the rgp120. EPI with rgp120 using sugar and gold particles as carrier resulted in differential antigen entry into the LCs and differential IgG subclass antibody and cellular immune responses. EPI may serve as a useful tool to evaluate vaccine potential of the rgp120 protein.
Vaccine 2002 Aug 19;20(25-26):3148
Gene gun bombardment with gold particles displays a particular Th2-promoting signal that over-rules the Th1-inducing effect of immunostimulatory CpG motifs in DNA vaccines.
Weiss R, Scheiblhofer S, Freund J, Ferreira F, Livey I, Thalhamer J.
Institute of Chemistry and Biochemistry, University of Salzburg, Hellbrunner Street 34, A-5020, Salzburg, Austria
The mode of administering a DNA vaccine can influence the type of immune response induced by the vaccine. For instance, application of a DNA vaccine by gene gun typically induces a Th2-type reaction, whereas needle inoculation triggers a Th1 response. It has been proposed that the approximately 100-fold difference in the amount of DNA administered by these two methods is the critical factor determining whether a Th1 or a Th2 response is made. To test this hypothesis, BALB/c mice were immunized with two plasmid DNA constructs encoding different proteins (OspC/ZS7 of Borrelia burgdorferi and Bet v 1a, the major birch pollen allergen). Both vaccines were applied by needle and/or by gene gun immunization at the same and at different sites of injection. An analysis of the IgG subclass distribution and measurement of IFN-gamma after antigen-specific lymphoproliferation does not support the widely accepted view that Th2-type immunity induced by gene gun application is solely due to the low amount of injected plasmid DNA thus falling below the critical concentration of CpG motifs necessary for Th1-induction. Furthermore, the data also indicate a strong and even systemic adjuvant effect of the gene gun shot itself.
etc., etc., etc. |
