A novel therapeutic multiepitope vaccine based on oncoprotein E6 and E7 of HPV 16 and 18: An in silico approach.

Introduction: The current vaccine strategies to prevent cervical cancer are effective only for individuals unexposed to HPV, lacking therapeutic effects against pre-existing infections. Multiepitope vaccines, using an immunoinformatic approach, are promising against tumors and viral infections because of their high specificity, safety, and stability, as well as the cheap cost of development. Methods: This study employed computer-based immunoinformatic analysis to design therapeutic multiepitope vaccines against cervical cancer using oncoproteins E6 and E7 of HPV 16 and 18. Several immunoinformatic tools were applied to analyze potential vaccine constructs capable of stimulating immune responses against both oncoproteins. Results: The constructed vaccine exhibited antigenic, immunogenic, nonallergenic, nontoxic, stable, and soluble characteristics. Additionally, it effectively interacted with TLR2 and TLR4, showing high binding capacity. Computational analysis indicated the vaccine could induce immune responses through the elevation of cytokine levels after the third injection, antibody production, activation of memory B and T cells, and promotion of increased dendritic cell counts. Conclusion: The novel multiepitope vaccine based on E6 and E7 presented as a promising candidate for combating HPV infections and associated cervical cancer. Further in vitro and in vivo studies were essential to validate the efficacy and safety of the vaccine.

Expression of MAGE A1 to MAGE A10 in the Forceps Biopsy and Bronchoalveolar Lavage Specimens from Patients with the Central Lung Tumor.

OBJECTIVE: The objective was to evaluate the expression of the MAGE A subtypes family in the central lung tumor patients from the forceps biopsy (FB) and bronchoalveolar lavage (BAL) specimens and to analyze its association with the histopathological examination. METHODS: An observational study was conducted on 32 FB and 43 BAL specimens from patients with central lung tumors. All samples were assessed for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression by reverse transcription (RT) polymerase chain reaction (PCR) and samples showing a positive result were examined for MAGE A subtypes family expression by nested-RT PCR. RESULT: The MAGE A1 to MAGE A10 genes were highly expressed in the FB and BAL specimens from patients with central lung tumors. The MAGE A1 to MAGE A10 gene and MAGE A1 to MAGE A6 gene were expressed in 60/75 (80%) and 16/75 (21.3 %), respectively. MAGE A8, MAGE A9, and MAGE A10 were the most commonly expressed. In FB specimens diagnosed without malignant cells, MAGE A1 to MAGE A10 and MAGE A1 to MAGE A6 were positive in 16/18 (88.9 %) and 1/18 (5.6 %), respectively. In all BAL specimens were diagnosed with no malignant cells, but MAGE A1 to MAGE A10 and MAGE A1 to MAGE A6 showed positive results in 36/43 (83.7%) and 9/43 (20.9%) %), respectively. There was a significant association between MAGE A1 to MAGE A6 expression with histopathological diagnosis. CONCLUSION: The MAGE A subtype family genes are highly expressed in central lung tumor patients from FB and BAL specimens, even in specimens that were diagnosed with no malignant cells. All BAL specimens were diagnosed as no malignant cells, but expression of the MAGE A subfamily genes was found in more than 80% of the specimens. These observations suggest that combining histopathological and molecular examination could improve the diagnosis of lung malignancy.

The MAGE A1-A10 Expression associated with Histopathological Findings of Malignant or Non-Malignant Cells in Peripheral Lung Tumors.

OBJECTIVE: The objective was to evaluate the expression of melanoma antigen (MAGE) A from A1 to 10 (A1-10) and the individual MAGE A family in the peripheral lung tumors and to analyze its association with histopathological findings. METHODS: A cross-sectional study was conducted on 67 samples of peripheral lung tumor obtained by core biopsies from patients with clinical diagnoses such as lung and mediastinal tumors. The specimens were divided into two, one to perform histopathological diagnosis and the last for mRNA MAGE A examination. A Nested polymerase chain reaction (PCR) was performed using universal primer, MF10/MR10 and MF10/MR12. The collected data were analyzed by appropriate statistical techniques. RESULT: The histopathological finding showed 41 (61.2 %) of specimens as malignant cells and 26 (38.8 %) of specimens as non-malignant cells. MAGE A1-10 was expressed at 47 (70.1 %) and MAGE A1-6 was expressed at 25 (37.3 %) of specimens. In a malignant cell, MAGE A1-10 and MAGE A1-6 were expressed at 33 (80.5 %) and 19 (46.3 %), respectively. In non-malignant cells, MAGE A1-10 and MAGE A1-6 were expressed at 14 (53.9 %) and 6 (23.1 %,) respectively. The MAGE A1-10 and MAGE A8 expressions were significantly associated with histopathological findings of malignant or non-malignant cells. The sensitivity, specificity, and diagnostic accuracy of MAGE A1-10 were 80.5 %, 46.2 %, and 67.2 %, respectively; while for MAGE A8 were 41.5 %, 88.5 %, and 59.7 %, respectively. CONCLUSION: The MAGE A1-10 expression was the most commonly detected and associated with the histopathological finding. Moreover, it was more sensitive and specific and had higher diagnostic accuracy than others. Therefore, the MAGE A1-10 assay may improve the accuracy of the diagnosis of malignancy in peripheral lung tumors.