Single Dose of a Polyanhydride Particle-Based Vaccine Generates Potent Antigen-Specific Antitumor Immune Responses

Abstract

Many factors affect vaccine efficacy. One of the most salient is the frequency and intervals of vaccine administration. In this study, we assessed the vaccine administration modality for a recently reported polyanhydride-based vaccine formulation, shown to generate antitumor activity. Polyanhydride particles encapsulating ovalbumin (OVA) were prepared using a doubleemulsion technique and subcutaneously delivered to mice either as a single-dose or as prime-boost vaccine regimens in which two different time intervals between prime and boost were assessed (7 or 21 days). This was followed by measurement of cellular and humoral immune responses, and subsequent challenge of the mice with a lethal dose of E.G7-OVA cells to evaluate tumor protection. Interestingly, a single dose of the polyanhydride particle-based formulation induced sustained OVA-specific cellular immune responses just as effectively as the prime-boost regimens. In addition, mice receiving singledose vaccine had similar levels of protection against tumor challenge compared with mice administered prime-boosts. In contrast, measurements of OVA-specific IgG antibody titers indicated that a booster dose was required to stimulate strong humoral immune responses, since it was observed that mice administered a prime-boost vaccine had significantly higher OVA-specific IgG 1 serum titers than mice administered a single dose. These findings indicate that the requirement for a booster dose using these particles appears unnecessary for the generation of effective cellular immunity.

Therapeutic Perspectives on the Modulation of G-Protein Coupled Estrogen Receptor, GPER, Function

“…Through diffusion and degradation of the polymer, the drug can be released in a controlled manner to the target cancer (149). Polymers used to prepare these particles include but are not limited to poly lactic-coglycolic acid (149), polysulfenamides (150), and polyanhydrides (151). Agents that can be loaded into the particles include proteins such as cancer antigens (152), nucleic acid based molecules like plasmid DNA (153) and CpG (154) and small molecule drugs like paclitaxel and doxorubicin (149,155).…”

Pentaerythritol-based lipid A bolsters the antitumor efficacy of a polyanhydride particle-based cancer vaccine

“…terms of stimulating strong immune responses, we and others have found that simultaneous delivery of the antigen and adjuvant using independently loaded particles results in similar enhancement of immune responses 17,50,54,55 . This is because separately encapsulated antigen and adjuvant will not necessarily remain segregated in vivo as both types of particle formulations could be internalized by the same DCs, which generally have the capacity to internalize more than one particle at a time 56 . Specifically, our group has previously demonstrated that co-loading PELA and OVA into the same poly(lactide-co-glycolide)-based particles generated similar cellular immune responses and provided similar tumor protection to independently loaded particles 50 .…”

Thiophene Derivative‐Loaded Nanoparticles Mediate Anticancer Activity Through the Inhibition of Kinases and Microtubule Assembly

“…Comparison of survival curves was initially performed by the Log‐rank (Mantel‐Cox) test using GraphPad Prism 8 (GraphPad Software, La Jolla, CA), and further statistical analysis was carried out by pairwise comparisons, and data were analyzed using Log‐rank test (Tukey‐Kramer adjusted) using SAS 9.4 software. [ 45 ] In all tests, differences were considered statistically significant when P < 0.05.…”