Evaluation of a diphtheria and tetanus PLGA microencapsulated vaccine formulation without stabilizers.
Polymeric microspheres containing diphtheria and tetanus toxoids were prepared without protein stabilizers. A vaccine containing 2 Lf(tetanus) and 0.4 Lf(diphtheria) was injected either in BALB/c mice or in guinea-pigs. As control, a group received the alum-adsorbed unencapsulated toxoids. In mice, on day 44 one group and control received a booster and at day 111 the other group received the same booster dose. Before de booster, all groups had very low neutralizing antibodies, as determined by Toxin binding inhibition assay. One week after booster all groups had high antibody titers, especially those immunized with microencapsulated vaccine, which were at least 5 times higher than those immunized with alum vaccine for both antigens. Besides, guinea pigs receiving lower dose had antibodies titers as high as 60 UI/mL, and 30 times higher than those immunized with alum vaccine. Therefore by using an encapsulated vaccine without any kind of protein stabilizer we were able to induce in vivo protective responses irrespective of observed in vitro protein degradation by HPLC. Manipulating the vaccination schedule at the same time to the toxoids encapsulation does not only increase the antibody titers but also their specificity.
Quintilio
Wagner
W
Quality Control Service, Instituto Butantan, Av. Dr Vital Brazil, 1500 SP 05503-900 Brazil. wagner@butantan.gov.br
Takata
Célia S
CS
Sant'Anna
Osvaldo A
OA
da Costa
Maria Helena B
MH
Raw
Isaías
I
D000276:Adjuvants, Immunologic; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D001682:Biological Availability; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D022422:Diphtheria-Tetanus Vaccine / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D004339:Drug Compounding; D005260:Female; D006168:Guinea Pigs; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D014611:Vaccination / Q000379:methods
D000276:Adjuvants, Immunologic; D000906:Antibodies; D004168:Diphtheria Toxoid; D022422:Diphtheria-Tetanus Vaccine; D007074:Immunoglobulin G; D013745:Tetanus Toxoid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid