Injectable silicone implants as vaccine delivery vehicles.
Injectable silicone implants were assessed as vaccine delivery vehicles in sheep, using either the model antigen avidin or Clostridium tetani and Clostridium novyi toxoids. Two types of implant were compared, the matrix type, that has been shown to deliver antigen in vitro in a first-order profile over approximately 1 month, and the covered rod type, that delivers antigen for several months in a zero-order profile. The implants were prepared using lyophilized antigen and adjuvant (in this case, recombinant ovine interleukin-1beta; rovIL-1beta) and manufactured in the absence of extremes of temperature or pH or the use of organic solvents. Use of the matrix type implant was capable of inducing antibody responses equivalent to those induced by conventional vaccination with aluminium hydroxide adjuvant ("alum"). The use of the covered rod implants, that release very low levels of antigen over a long period, induced responses that were markedly enhanced over the alum control groups. The covered rod implant also favoured production of both IgG1 and IgG2 isotypes in contrast to responses of matrix-vaccinated sheep and conventionally vaccinated control sheep in which IgG1 predominated. Prolonged duration of the antibody response was also observed following vaccination with covered rod implants. Dose-response analysis using the matrix implant demonstrated a trend towards improved responses for lower antigen doses. Clostridial vaccination of sheep showed that protective antibody titres up to 4-fold higher than for alum-adjuvanted groups could be induced by administering the antigen in the covered rod implant. Responses elicited by all implant groups were dependent on the inclusion of adjuvant into the implant formulation.
Lofthouse
S A
SA
Centre for Animal Biotechnology, School of Veterinary Science, The University of Melbourne, 3010 Vic., Australia. sal@unimelb.edu.au
Kajihara
M
M
Nagahara
S
S
Nash
A
A
Barcham
G J
GJ
Sedgmen
B
B
Brandon
M R
MR
Sano
A
A
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage; D001360:Avidin / Q000008:administration & dosage / Q000276:immunology; D003013:Clostridium / Q000276:immunology; D003017:Clostridium tetani / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D016503:Drug Delivery Systems; D004343:Drug Implants; D005260:Female; D007375:Interleukin-1 / Q000008:administration & dosage; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage; D012756:Sheep; D012828:Silicones; D013745:Tetanus Toxoid / Q000008:administration & dosage; D014121:Toxoids / Q000008:administration & dosage; D014612:Vaccines / Q000008:administration & dosage*
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000941:Antigens; D004343:Drug Implants; D007375:Interleukin-1; D011994:Recombinant Proteins; D012828:Silicones; D013745:Tetanus Toxoid; D014121:Toxoids; D014612:Vaccines; D001360:Avidin