Experimental Validation of MHC Class I and II Peptide-Based Potential Vaccine Candidates for Human Papilloma Virus Using Sprague-Dawly Models.

Human papilloma virus (HPV) causes cervical and many other cancers. Recent trend in vaccine design is shifted toward epitope-based developments that are more specific, safe, and easy to produce. In this study, we predicted eight immunogenic peptides of CD4+ and CD8+ T-lymphocytes (MHC class I and II as M1 and M2) including early proteins (E2 and E6), major (L1) and minor capsid protein (L2). Male and female Sprague Dawly rats in groups were immunized with each synthetic peptide. L1M1, L1M2, L2M1, and L2M2 induced significant immunogenic response compared to E2M1, E2M2, E6M1 and E6M2. We observed optimal titer of IgG antibodies (>1.25 g/L), interferon-γ (>64 ng/L), and granzyme-B (>40 pg/mL) compared to control at second booster dose (240 µg/500 µL). The induction of peptide-specific IgG antibodies in immunized rats indicates the T-cell dependent B-lymphocyte activation. A substantial CD4+ and CD8+ cell count was observed at 240 µg/500 µL. In male and female rats, CD8+ cell count for L1 and L2 peptide is 3000 and 3118, and CD4+ is 3369 and 3484 respectively compared to control. In conclusion, we demonstrated that L1M1, L1M2, L2M1, L2M2 are likely to contain potential epitopes for induction of immune responses supporting the feasibility of peptide-based vaccine development for HPV.

Association study of NAT2 gene polymorphism and risk of oral cancer in Southern Punjab, Pakistan.

OBJECTIVE: To investigate the single nucleotide polymorphic variations of N-acetyltransferase 2, phase-II metabolising enzyme, and associated risk factors for oral cancer. METHODS: The case-control study was conducted from November 2017 to April 2018 after approval from the Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, Multan, Pakistan, and comprised oral cancer patients and healthy controls. Single nucleotide polymorphism of the N-acetyltransferase 2 gene associated with oral cancer was analysed. Factors assessed using tetra-primer amplification refractory mutation system polymerase chain reaction included age, smoking, naswar, betel leaves and nuts. RESULTS: Of the 201 subjects, 94(47%) were patients and 107(53%) were controls, while 108(54%) were aged 10-30 years. Single nucleotide polymorphism rs1208 of N-acetyltransferase 2 gene was primarily A803G and Lys268Arg, with allelic frequency of G/A. Age range 51-70 was significantly (p=0.00001) associated with the prevalence of oral cancer in terms of genotypic relationship with A803G. Substantial allelic association was found between the gene and oral cancer (p=0.006895). Smoking increased the cacner risk 7-fold (odds ratio: 7.0). CONCLUSIONS: The genetic variant of N-acetyltransferase 2 rs1208 was found to be significantly associated with oral cancer progression and development of associated risk factors.

Designing of Potential Polyvalent Vaccine Model for Respiratory Syncytial Virus by System Level Immunoinformatics Approaches.

BACKGROUND: Respiratory syncytial virus (RSV) infection is a public health epidemic, leading to around 3 million hospitalization and about 66,000 deaths each year. It is a life-threatening condition exclusive to children with no effective treatment. METHODS: In this study, we used system-level and vaccinomics approaches to design a polyvalent vaccine for RSV, which could stimulate the immune components of the host to manage this infection. Our framework involves data accession, antigenicity and subcellular localization analysis, T cell epitope prediction, proteasomal and conservancy evaluation, host-pathogen-protein interactions, pathway studies, and in silico binding affinity analysis. RESULTS: We found glycoprotein (G), fusion protein (F), and small hydrophobic protein (SH) of RSV as potential vaccine candidates. Of these proteins (G, F, and SH), we found 9 epitopes for multiple alleles of MHC classes I and II bear significant binding affinity. These potential epitopes were linked to form a polyvalent construct using AAY, GPGPG linkers, and cholera toxin B adjuvant at N-terminal with a 23.9 kDa molecular weight of 224 amino acid residues. The final construct was a stable, immunogenic, and nonallergenic protein containing cleavage sites, TAP transport efficiency, posttranslation shifts, and CTL epitopes. The molecular docking indicated the optimum binding affinity of RSV polyvalent construct with MHC molecules (-12.49 and -10.48 kcal/mol for MHC classes I and II, respectively). This interaction showed that a polyvalent construct could manage and control this disease. CONCLUSION: Our vaccinomics and system-level investigation could be appropriate to trigger the host immune system to prevent RSV infection.

Differences in Food-at-Home Spending for SNAP and Non-SNAP Households Given Geographic Price Variation.

BACKGROUND: As the largest nutrition safety net program in the United States, the Supplemental Nutrition Assistance Program (SNAP) enhances food security by providing low-income households with benefits for food-at-home (FAH) spending. A large literature finds a positive effect of SNAP on FAH spending, but it is unclear whether this relationship varies with area-level prices. SNAP benefits do not explicitly account for price variation across the contiguous United States. OBJECTIVE: Our objectives were to examine the SNAP/non-SNAP difference in FAH spending for households with varying levels of cash income and propensity for SNAP participation and to determine whether this difference varied with area-level prices. DESIGN/PARTICIPANTS: Cross-sectional data on 2,524 SNAP and non-SNAP households with cash income at or below 185% of the Federal Poverty Level were obtained from the National Household Food Acquisition and Purchase Survey. MAIN OUTCOME MEASURES: The outcome was FAH spending relative to the maximum SNAP benefit corresponding to household size. STATISTICAL ANALYSES PERFORMED: Households were grouped into quintiles based on estimated propensity of SNAP participation. Regression models included interactions between a SNAP participation indicator, a continuous price index for all goods and services, and propensity score quintile indicators. RESULTS: According to some models, the SNAP/non-SNAP spending difference was positive, on average. Among households that tended to have lower cash income and higher propensity of SNAP participation, FAH spending relative to the maximum benefit was 29 to 30 percentage points higher for SNAP households compared to low-income non-SNAP households (P≤0.05). The spending difference was similar across areas with different price levels. CONCLUSIONS: SNAP households spent more on FAH compared to low-income non-SNAP households. This association did not vary with area-level prices. Beyond food spending outcomes, future research could extend this work to understand SNAP's role in promoting food security and other outcomes, given geographic price variation.