Controlled release microparticles as a single dose diphtheria toxoid vaccine: immunogenicity in small animal models

An experimental divalent vaccine based on biodegradable microspheres induces protective immunity against tetanus and diphtheria

“…26 More commonly, toxin neutralization assays with mixtures of immune sera and toxins injected in naïve animals have been utilized to confirm functional Ab. 4,5,24 In our study, the experimental microsphere-based divalent vaccines provided better protection against diphtheria and tetanus upon challenge than did a single injection with the control divalent vaccine (Figure 3). Differences in protection between microsphere preparations were observed mainly for diphtheria.…”

“…This was because persistence of toxin-neutralizing anti-TT and anti-DT Ab over a year has already been demonstrated with similar formulations. 4,5,7,24 In these previous experiments, Ab against microencapsulated TT or DT revealed maximum titers between week 8 and 16 postimmunization, which did not change substantially thereafter. Furthermore, the long-term potential of TT-containing microspheres has been demonstrated in mice and guinea pigs by boosting the animals a year after priming.…”

“…[1][2][3][4][5] As a consequence of the promising preclinical data, the first human trial with a microsphere-based tetanus vaccine is now envisaged. 6 Previous studies have addressed technologic issues, such as the process of microencapsulation and antigen stability (reviewed in ref.…”

“…11 Furthermore, the protective efficacy of microsphere-based vaccines has not always been adequately confirmed. Although several investigations 2,[4][5][6] have demonstrated the induction of neutralizing antibodies (nAb) and nAb against tetanus and diphtheria toxins generally correlate well with protection in the guinea pig model for currently licensed vaccines, 12,13 protective immunity is ideally demonstrated by a direct challenge with the infectious agent.…”

Single-injection vaccines: Progress, challenges, and opportunities

“…These particles can be injected intramuscularly or subcutaneously at one time point, but deliver their contents with a variety of release profiles over days, weeks, months, or even years depending on formulation and material properties [26,[29][30][31][32][33][34]. While an oral formulation would be ideal for ease of administration [35], vaccines administered via this method may only provide mucosal immunity (rather than systemic) and can be more difficult to reliably administer to infants [36].…”