RESUMO
Persistent infection with high-risk human papillomavirus (HPV) is widely recognized as the primary cause of cervical and other malignant cancers. There are six licensed prophylactic vaccines available against HPV, but none of them shows any significant therapeutic effect on pre-existing infections or lesions. Thus, a prophylactic vaccine also endowed with therapeutic activity would afford protection regardless of the vaccine recipients HPV-infection status. Here, we describe the refinement and further potentiation of a dual-purpose HPV nanoparticle vaccine (hereafter referred to as cPANHPVAX) relying on eight different HPV L2 peptide epitopes and on the E7 oncoantigens from HPV16 and 18. cPANHPVAX not only induces anti-HPV16 E7 cytotoxic T-cell responses in C57BL/6 mice, but also anti-HPV18 E7 T-cell responses in transgenic mice with the A2.DR1 haplotype. These cytotoxic responses add up to a potent, broad-coverage humoral (HPV-neutralizing) response. cPANHPVAX safety was further improved by deletion of the pRb-binding domains of E7. Our dual-purpose vaccine holds great potential for clinical translation as an immune-treatment capable of targeting active infections as well as established HPV-related malignancies, thus benefiting both uninfected and infected individuals.
RESUMO
This study discusses the retention of Ni(II) by Arthrobacter viscosus supported on zeolite 13 X in batch mode and in continuous mode, at laboratory scale and at pilot scale. The maximum adsorption capacities of 28.37, 20.21 and 11.13 mg/g were recorded for lab scale batch, for continuous lab scale minicolumns and for pilot scale bioreactors, respectively. The Sips isotherm and pseudo second order kinetics described well the observations registered in batch assays. The Adams-Bohart, Thomas and Yoon-Nelson models were applied to data obtained with the pilot scale bioreactor and a good fit was reached for Adams-Bohart and for Yoon-Nelson models. A fed-batch was performed at lab scale and the applicability of the biofilm in continuous mode for the described purpose was confirmed. The sorption mechanism was investigated in detail through FTIR, SEM and EDX analyses.