Alternative Methods of Vaccine Delivery: An Overview of Edible and Intradermal Vaccines.

Vaccines are recognized worldwide as one of the most important tools for combating infectious diseases. Despite the tremendous value conferred by currently available vaccines toward public health, the implementation of additional vaccine platforms is also of key importance. In fact, currently available vaccines possess shortcomings, such as inefficient triggering of a cell-mediated immune response and the lack of protective mucosal immunity. In this regard, recent work has been focused on vaccine delivery systems, as an alternative to injectable vaccines, to increase antigen stability and improve overall immunogenicity. In particular, novel strategies based on edible or intradermal vaccine formulations have been demonstrated to trigger both a systemic and mucosal immune response. These novel vaccination delivery systems offer several advantages over the injectable preparations including self-administration, reduced cost, stability, and elimination of a cold chain. In this review, the latest findings and accomplishments regarding edible and intradermal vaccines are described in the context of the system used for immunogen expression, their molecular features and capacity to induce a protective systemic and mucosal response.

Role and potential therapeutic use of antibodies against herpetic infections.

BACKGROUND: The cellular adaptive response directed against herpesviruses is widely described in the scientific literature as a pivotal component of the immune system able to control virus replication. The role of humoral immunity remains unclear and controversial. AIMS: Discussing the role of adaptive immunity in herpesvirus infection control, highlighting the potential role of the humoral branch of immunity through the description of human monoclonal antibodies directed against herpesviruses. SOURCES: PubMed search for relevant publications related to protective immunity against Herpesviridae. CONTENT: This review describes the role of adaptive immunity directed against Herpesviridae, focusing on the human humoral response naturally elicited during their infections. Given the ever-increasing interest in monoclonal antibodies as novel therapeutics, the contribution of humoral immunity in controlling productive infection, during both primary infection and reactivations, is discussed. IMPLICATIONS: Human monoclonal antibodies directed against the different Herpesviridae species may represent novel molecular probes to further characterize the molecular machinery involved in herpesvirus infection; and allow the development of novel therapeutics and effective vaccine strategies.

Antimutagenic and antigenotoxic effects of vegetable matrices on the activity of pesticides.

Two in vitro tests, one to detect bacterial mutagenicity (Ames test) on Salmonella typhimurium TA98, TA100, and TA1535 and the other the primary DNA damage (SOS Chromotest) on Escherichia coli PQ37, were applied to determine the overall genotoxic activity of 12 pesticides (azinphos methyl, chlorothalonil, chlorphyriphos ethyl, chlorphyriphos methyl, lambda-cyhalothrin, cypermethrin, cyprodinil, fenazaquin, fludioxonil, indoxacarb, iprodione and penconazol). These were detected by gas chromatography (GC) analysis with electron capture (ECD) and nitrogen phosphorus detection (NPD) in 18 samples of vegetables. Some extracts of vegetables, found positive for pesticides with GC, were subjected to the Ames test and SOS Chromotest to evaluate the possible antimutagenic and/or antigenotoxic effects of vegetable matrices. The same bioassays were also performed on the mixtures of pesticides found in these samples to evaluate whether interactions could occur between pesticides and be responsible for the possible antimutagenic and/or antigenotoxic effects of the contaminated matrices. Experiments were also carried out to compare the results found for contaminated vegetables with their content of antioxidant components. Significant differences in mutagenicity and genotoxicity were found among the pesticides selected for this study. Of the 12 pesticides tested, only azinphos methyl, cyprodinil, fludioxonil and iprodione were found to be positive for both S. typhimurium and E. coli. No mutagenic/genotoxic activity was found in the extracts of vegetables contaminated by pesticides. S. typhimurium TA1535 showed a strong positive mutagenic effect for the mixtures of pesticides while they were not able to induce the SOS system. The data concerning the content of polyphenols and the total reducing activity of the contaminated vegetables indicated high amounts of antioxidants that could explain the inhibitory effect on the activity of pesticides shown by vegetables.

Fine needle aspiration of the pancreas. A five-year experience.

Forty fine needle aspiration (FNA) biopsies of the pancreas were performed on 37 patients with a radiologic suspicion of malignancy; 32 aspirations were guided by ultrasound, 2 were guided by CT, and 6 were obtained intraoperatively. A pathologist read a rapid-stained smear of the initial aspirate as the procedure was performed and triaged specimens for routine cytologic, cell block and ultrastructural study in solid lesions plus carcinoembryonic antigen (CEA) assay and amylase study in cystic lesions. Purulent material was studied by gram staining and culture. The overall sensitivity in the series was 81%, with a specificity of 100%. No complications were noted. Ultrastructural examination improved the diagnostic accuracy in two cases. Assays for CEA and amylase in "cyst fluids" differentiated true cysts and cystadenocarcinoma from pseudocysts. Maximum utilization of the material aspirated was useful in diagnosing the etiology of solid and cystic pancreatic masses.

Fine needle aspiration of the liver.

A total of 81 transhepatic fine needle aspiration (FNA) biopsies were performed on 78 patients to rule out focal or diffuse neoplastic disease; 87.6% were performed with ultrasound guidance, 6.1% with CT guidance, 3.7% intraoperatively and 1 using fluoroscopy during percutaneous transhepatic cholangiography. Smears of the aspirated samples were cytologically evaluated with clinical and radiologic correlation; in addition, histologic examination of cell blocks was performed in 46% of the cases, ultrastructural examination in 34% of the cases and peroxidase-antiperoxidase staining in 3 cases. Ultrastructural definition of the type of malignancy was possible in 24 cases (29%). Minor complications in two patients were pain and tenderness at the puncture site. The sensitivity for malignancy was 91%, the specificity was 100%, the predictive value of positive results was 100%, and the predictive value of negative results was 73%. This series demonstrates that FNA biopsy with ultrasound guidance can provide an accurate diagnosis of malignancy and may preempt a lengthy workup in the search for a primary tumor.

Carcinoembryonic antigen in effusions. A diagnostic adjunct to cytology.

A total of 189 effusion specimens (100 benign and 89 malignant) submitted for cytologic examination were assayed for carcinoembryonic antigen (CEA) by an enzyme immunoassay to determine whether the addition of CEA evaluation to cytologic study would improve the diagnostic accuracy for the detection of malignancy. The sensitivity and specificity were 78% and 90%, respectively, for a cytologic diagnosis of malignancy and 68% and 99%, respectively, for a positive CEA (greater than 5 ng/mL). CEA assay was negative in the most common epithelial malignancies of the female genital tract (15 of 17 cases), mesotheliomas (5), lymphomas (7) and alveolar-cell carcinoma of lung (1). CEA assay was positive in 55 of 89 cases of malignancy, including 14 cases with cytologically negative malignant effusions. The CEA assay sensitivity for lung carcinoma (95% for adenocarcinoma, 100% for oat-cell carcinoma and 100% for carcinosarcoma), breast carcinoma (95%), and gastrointestinal carcinoma (100%) were all over 90%. No significant difference in the levels of CEA was noted between gastrointestinal and lung adenocarcinomas. Oat-cell carcinomas and squamous-cell carcinomas had lower values. In cases of an effusion with an unknown primary, an elevated CEA in the fluid is diagnostic of metastatic carcinoma arising from the breast, lung or gastrointestinal tract.

Immunoradiometric assay of CA 125 in effusions. Comparison with carcinoembryonic antigen.

The levels of CA 125 antigen were measured in 167 effusions from 150 patients using radioimmunoassay, and the results compared with the levels of carcinoembryonic antigen (CEA) in the fluids. This study was carried out to test a hypothesis that measuring the combined levels of selected tumor associated antigens in effusions could predict the primary source of malignancy. The results indicate that an elevated fluid CA 125 level (greater than 14,000 U/ml-68,000 U/ml) and a negative fluid CEA level (less than 5 ng/ml) is suggestive of serous and endometrioid carcinoma of ovary, and adenocarcinoma of the endometrium and fallopian tube. Alternatively, an elevated fluid CEA level (14 ng/ml-600 ng/ml) and a negative CA 125 level (20-5000 U/ml) is seen in metastatic carcinomas of breast, lung, gastrointestinal tract, and mucinous cystadenocarcinoma. Lymphomas, melanomas, and benign effusions are negative for both antigens. The combined use of CEA and CA 125 antigen in fluids is useful in the differential diagnosis of adenocarcinoma of unknown primary.

Diagnosis of cystic lesions of the pancreas: a biochemical and cytologic analysis of material obtained utilizing radiographic or intraoperative technique.

The widespread use of imaging modalities may detect clinically unsuspected "pancreatic cysts" in which the differential diagnoses include pseudocysts, cystic neoplasms, necrotic carcinomas, abscesses, and, uncommonly, islet cell tumors. Accurate preoperative diagnosis requires clinical, radiologic, microbiologic, cytologic, and biochemical studies. Material obtained by fine-needle aspiration from cysts can be triaged for cytology, amylase, and carcinoembryonic antigen (CEA) studies. The four cases described suggest that an elevated fluid CEA is specific for carcinoma, and an elevated amylase and negative CEA suggests pseudocysts, while both amylase and CEA are negative in abscesses. Thus, "cystic lesions of pancreas" can be accurately diagnosed in cases in which radiologic and cytologic studies are inconclusive. The routine inclusion of these tests with cytologic study should be encouraged to obviate unnecessary surgery for diagnostic purposes.