Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as an adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies

Abstract

Microspheres composed of biocompatible, biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) and staphylococcal enterotoxin B (SEB) toxoid were evaluated as a vaccine delivery system when subcutaneously injected into mice. As measured by circulating immunoglobulin G (IgG) antitoxin titers, the delivery of SEB toxoid via DL-PLG microspheres, 1 to 10 i,m in diameter, induced an immune response which was approximately 500 times that seen with nonencapsulated toxoid. The kinetics, magnitude, and duration of the antitoxin response induced with microencapsulated toxoid were similar to those obtained when an equal toxoid dose was administered as an emulsion with complete Freund adjuvant. However, the microspheres did not induce the inflammation and granulomata formation seen with complete Freund adjuvant. The adjuvant activity of the microspheres was not dependent on the superantigenicity of SEB toxin and was equally effective at potentiating circulating IgG antitrinitrophenyl levels in response to microencapsulated trinitrophenyl-keyhole limpet hemocyanin. Empty DL-PLG microspheres were not mitogenic, and SEB toxoid injected as a mixture with empty DL-PLG microspheres was no more effective as an immunogen than toxoid alone. Antigen-containing microspheres 1 to 10 jim in diameter exhibited stronger adjuvant activity than those > 10 ,um, which correlated with the delivery of the 1to 10-,um, but not the >10-jim, microspheres into the draining lymph nodes within macrophages. The antibody response induced through immunization with microencapsulated SEB toxoid was protective against the weight loss and splenic Vi8' T-cell expansion induced by intravenous toxin administration. These results show that DL-PLG microsphere vaccine delivery systems, which are composed of pharmaceutically acceptable components, possess a strong adjuvant activity for their encapsulated antigens.

Technologies for enhanced efficacy of DNA vaccines

“…Synthetic polymers such as poly(vinylpyridine), polylactide-co-glycolides (PLG) and polylactide-co-glycolide acid (PLGA) have a long history of biocompatibility and safety in humans [55,56]. Encapsulation of antigens into PLG microparticles was first demonstrated in the early 1990s [57]. Encapsulation of DNA helps protect the plasmid from nuclease degradation and provides prolonged release.…”

Nanotechnology in vaccine delivery

“…A second proposed mechanism is attributed to the particulate nature of the aluminum salts. Because particles smaller than 10 μm are more easily phagocytosed by macrophages and dendritic cells [29,30], uptake of the antigen adsorbed to a particulate adjuvant should be increased (relative to antigen in solution) thereby improving the efficiency of antigen recognition and presentation. The third suggested mechanism of action is by a direct stimulation of the immune system through enhanced cytokine production.…”

“…For example, microparticles are approximately the same size as many pathogens that the immune system is equipped to attack [37]. Additionally, larger particles generally provide a longer duration of antigen release than equivalent smaller ones, which can have a dramatic influence on immunogenicity [30,[38][39][40]. Moreover, microparticles have been shown to elicit both vigorous cellular [41] and humoral immunity [42].…”

Adjuvanted poly(lactic-co-glycolic) acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs

“…56 Consistent with the other studies, rapid uptake of NP-KAg vaccine by PAM cells was noticed, suggesting the ability of PLGA NPs to deliver vaccine Ags rapidly and efficiently to target cells. 50,64 Clinically, only mock (group 2) and KAg (group 3) vaccinated, MN184 virus-challenged pigs had irregular fever with reduced feed intake during the first 2 weeks postchallenge, and such physiological changes were absent in other pig groups. Though the MN184 virus is a virulent field kinetics.…”