Employing ATP as a New Adjuvant Promotes the Induction of Robust Antitumor Cellular Immunity by a PLGA Nanoparticle Vaccine.

Tumor vaccines based on synthetic human papillomavirus (HPV) oncoprotein E7 and/or E6 peptides have shown encouraging results in preclinical model studies and human clinical trials. However, the clinical efficacy may be limited by the disadvantages of vulnerability to enzymatic degradation and low immunogenicity of peptides. To further improve the potency of vaccine, we developed a poly(lactide-co-glycolide)-acid (PLGA) nanoparticle, which encapsulated the antigenic peptide HPV16 E744-62, and used adenosine triphosphate (ATP), one of the most important intracellular metabolites and an endogenous extracellular danger signal for the immune system, as a new adjuvant component. The results showed that PLGA nanoparticles increased the in vivo stability, lymph node accumulation, and dendritic cell (DC) uptake of the E7 peptide; in addition, ATP further increased the migration, nanoparticle uptake, and maturation of DCs. Preventive immunization with ATP-adjuvanted nanoparticles completely abolished the growth of TC-1 tumors in mice and produced long-lasting immunity against tumor rechallenge. When tumors were fully established, therapeutic immunization with ATP-adjuvanted nanoparticles still significantly inhibited tumor progression. Mechanistically, ATP-adjuvanted nanoparticles significantly improved the systemic generation of antitumor effector cells, boosted the local functional status of these cells in tumors, and suppressed the generation and tumor infiltration of immunosuppressive Treg cells and myeloid-derived suppressor cells. These findings indicate that ATP is an effective vaccine adjuvant and that nanoparticles adjuvanted with ATP were able to elicit robust antitumor cellular immunity, which may provide a promising therapeutic vaccine candidate for the treatment of clinical malignancies, such as cervical cancer.

Immunization with a 22-kDa outer membrane protein elicits protective immunity to multidrug-resistant Acinetobacter baumannii.

A. baumannii infections are becoming more and more serious health issues with rapid emerging of multidrug and extremely drug resistant strains, and therefore, there is an urgent need for the development of nonantibiotic-based intervention strategies. This study aimed at identifying whether an outer membrane protein with molecular weight of about 22 kDa (Omp22) holds the potentials to be an efficient vaccine candidate and combat A. baumannii infection. Omp22 which has a molecule length of 217 amino acids kept more than 95% conservation in totally 851 reported A. baumannii strains. Recombinant Omp22 efficiently elicited high titers of specific IgG in mice. Both active and passive immunizations of Omp22 increased the survival rates of mice, suppressed the bacterial burdens in the organs and peripheral blood, and reduced the levels of serum inflammatory cytokines and chemokines. Opsonophagocytosis assays showed in vitro that Omp22 antiserum had highly efficient bactericidal activities on clonally distinct clinical A. baumannii isolates, which were partly complements-dependent and opsonophagocytic killing effects. Additionally, administration with as high as 500 µg of Omp22 didn't cause obvious pathological changes in mice. In conclusion, Omp22 is a novel conserved and probably safe antigen for developing effective vaccines or antisera to control A. baumannii infections.