A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

Abstract

Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust T H 1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a T H 1-biased immune response, as demonstrated by a significant increase in antigen-specific IFNg-producing splenocytes, IgG2a titers, and proliferative capacity of CD8 C T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system.

3M‐052 as an adjuvant for a PLGA microparticle‐based Leishmania donovani recombinant protein vaccine

“…Consistent with those reports, our present study found that MPs enhanced T H 2‐associated IgG1 titers more than T H 1‐associated IgG2a/2b titers, and that an immunostimulatory adjuvant (3M‐052) was required to elicit increased T H 1‐biased humoral and cellular immune responses. Our group has observed similar results in previous studies with CpG oligodeoxynucleotide adjuvant and protein in MP formulations …”

Cysteine mutagenesis improves the production without abrogating antigenicity of a recombinant protein vaccine candidate for human chagas disease

“…The temperature was then reduced to 30 C and IPTG was added to a final concentration of 0.5 mM. After 5 hours of induction, cells were collected by centrifugation (12,227 x g, 4 C, 30 min) and biomass was collected and stored at ¡80 C. Frozen biomass of Tc24-WT C His was thawed and re-suspended in extraction Buffer A1 (30 mM Tris-HCl, 500 mM NaCl, 20 mM Imidazole, pH 8.0) at a ratio of 20 mL buffer per gram of wet cell paste.…”

“…Total DNA was isolated from blood and cardiac tissue using a DNeasy blood and tissue kit (Qiagen) and 4 ng of DNA from blood or 50ng of DNA from cardiac tissue was used in quantitative real-time PCR. 30,[48][49][50] Parasite equivalents were calculated based on a standard curve. Parasite burdens were compared using a Mann-Whitney test and p values less than 0.05 were considered significant.…”

“…29 In another study, Tc24 delivered using a nanoparticle delivery system significantly reduced peak parasitemia, cardiac parasite burden and inflammatory cell infiltrate. 30 This initial Tc24-WT antigen was expressed in E. coli and purified using a 2-step chromatography method. However, significant aggregation was observed during purification and storage of the protein, which would make reproducible scale-up of the protein and quality control more difficult and could impact immunogenicity and efficacy of the molecule as well.…”

Role of Tissue Engineering in COVID-19 and Future Viral Outbreaks

“…65 Biodegradable polymers, one of the primary workhorses as scaffold material in tissue engineering, have also been explored. PLGA nanoparticles drive Th1 immune response compared to no carriers and other biomaterials in a vaccine against Chagas disease in a murine model 66 and have also been explored for targeted delivery to specific immune populations. 67 PLGA microparticles in combination with a chitosan/peptide conjugate coating have also been used as a delivery system to target specific mucosal cells and to deliver a swine dysentery vaccine with elevated IgA and IgG production in mice.…”