scholarly journals Inclusion of the Guinea Pig Cytomegalovirus Pentameric Complex in a Live Virus Vaccine Aids Efficacy against Congenital Infection but Is Not Essential for Improving Maternal and Neonatal Outcomes

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2370
Author(s):  
Mark R. Schleiss ◽  
Claudia Fernández-Alarcón ◽  
Nelmary Hernandez-Alvarado ◽  
Jian Ben Wang ◽  
Adam P. Geballe ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Guinea Pig ◽  
Vertical Transmission ◽  
Transmission Model ◽  
Low Grade ◽  
Live Virus ◽  
Challenge Virus ◽  
Intact Group ◽  
Guinea Pig Cytomegalovirus ◽  
Pup Mortality

The development of a vaccine against congenital human cytomegalovirus (HCMV) infection is a major priority. The pentameric complex (PC) of virion envelope proteins gH, gL, UL128, UL130, and UL131A is a key vaccine target. To determine the importance of immunity to the homologous PC encoded by guinea pig cytomegalovirus (GPCMV) in preventing congenital CMV, PC-intact and PC-deficient live-attenuated vaccines were generated and directly compared for immunogenicity and efficacy against vertical transmission in a vertical transmission model. A virulent PC-intact GPCMV (PC/intact) was modified by galK mutagenesis either to abrogate PC expression (PC/null; containing a frame-shift mutation in GP129, homolog of UL128) or to delete genes encoding three MHC Class I homologs and a protein kinase R (PKR) evasin while retaining the PC (3DX/Δ145). Attenuated vaccines were compared to sham immunization in a two-dose preconception subcutaneous inoculation regimen in GPCMV seronegative Hartley guinea pigs. Vaccines induced transient, low-grade viremia in 5/12 PC/intact-, 2/12 PC/null-, and 1/11 3DX/Δ145-vaccinated animals. Upon completion of the two-dose vaccine series, ELISA titers for the PC/intact group (geometic mean titer (GMT) 13,669) were not significantly different from PC/null (GMT 8127) but were significantly higher than for the 3DX/Δ145 group (GMT 6185; p < 0.01). Dams were challenged with salivary gland-adapted GPCMV in the second trimester. All vaccines conferred protection against maternal viremia. Newborn weights were significantly lower in sham-immunized controls (84.5 ± 2.4 g) compared to PC/intact (96 ± 2.3 g), PC/null (97.6 ± 1.9 g), or 3DX/Δ145 (93 ± 1.7) pups (p < 0.01). Pup mortality in sham-immunized controls was 29/40 (73%) and decreased to 1/44 (2.3%), 2/46 (4.3%), or 4/40 (10%) in PC/intact, PC/null, or 3DX/Δ145 groups, respectively (all p < 0.001 compared to control). Congenital GPCMV transmission occurred in 5/44 (11%), 16/46 (35%), or 29/38 (76%) of pups in PC/intact, PC/null, or 3DX/Δ145 groups, versus 36/40 (90%) in controls. For infected pups, viral loads were lower in pups born to vaccinated dams compared to controls. Sequence analysis demonstrated that infected pups in the vaccine groups had salivary gland-adapted GPCMV and not vaccine strain-specific sequences, indicating that congenital transmission was due to the challenge virus and not vaccine virus. We conclude that inclusion of the PC in a live, attenuated preconception vaccine improves immunogenicity and reduces vertical transmission, but PC-null vaccines are equal to PC-intact vaccines in reducing maternal viremia and protecting against GPCMV-related pup mortality.

Pitfalls in Salivary Gland Fine-Needle Aspiration Cytology: Lessons From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology

2005 ◽  
Vol 129 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Jonathan H. Hughes ◽  
Emily E. Volk ◽  
David C. Wilbur
Keyword(s):  
Salivary Gland ◽  
Fine Needle Aspiration ◽  
False Positive ◽  
Interlaboratory Comparison ◽  
False Negative ◽  
Diagnostic Errors ◽  
Poor Performance ◽  
Needle Aspiration ◽  
Low Grade ◽  
Fine Needle

Abstract Context.—We use data from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology to identify common diagnostic errors in salivary gland fine-needle aspiration (FNA). Objective.—To identify salivary gland FNA cases with poor performance characteristics in the Nongynecologic Cytology Program surveys, so that the most common diagnostic pitfalls can be avoided. Design.—A retrospective review of the College of American Pathologists Nongynecologic Cytology Program's cumulative data from 1999 to 2003 revealed the most common false-positive and false-negative interpretations on FNA for common salivary gland lesions. Slides that performed poorly were then reviewed to identify the cytologic characteristics that may have contributed to their poor performance. Results.—A total of 6249 participant responses with general interpretations of benign (n = 4642) or malignant (n= 1607) were reviewed. The sensitivity and specificity of the participant responses for correctly interpreting the cases as benign or malignant were 73% and 91%, respectively. Benign cases with the highest false-positive rates were monomorphic adenoma (53% false-positive), intraparotid lymph node (36%), oncocytoma (18%), and granulomatous sialadenitis (10%). Malignant cases with the highest false-negative rates were lymphoma (57%), acinic cell carcinoma (49%), low-grade mucoepidermoid carcinoma (43%), and adenoid cystic carcinoma (33%). Selected review of the most discordant individual cases revealed possible explanations for some of the interpretative errors. Conclusions.—These data confirm the difficulty associated with interpretation of salivary gland FNA specimens. Cytologists should be aware of the potential false-positive and false-negative interpretations that can occur in FNAs from this organ site in order to minimize the possibility of diagnostic errors.

scholarly journals Immunohistochemical expression of vimentin, calponin and HHF-35 in salivary gland tumors

2007 ◽  
Vol 18 (3) ◽  
pp. 192-197 ◽  
Author(s):  
Roberta Barroso Cavalcante ◽  
Fernanda Ferreira Lopes ◽  
Andréa Soares Ferreira ◽  
Roseana de Almeida Freitas ◽  
Lélia Batista de Souza
Keyword(s):  
Salivary Gland ◽  
Myoepithelial Cells ◽  
Salivary Gland Tumors ◽  
Low Grade ◽  
Tubular Structures ◽  
Immunohistochemical Markers ◽  
Adenoid Cystic ◽  
Peripheral Cells ◽  
Diffuse Distribution ◽  
Labeling Pattern

Myoepithelial cells present a complex immunophenotype, with the expression of proteins varying according to the stage of normal or neoplastic differentiation of the cell. In order to evaluate the immunohistochemical markers expressed by these cells, a panel of antibodies composed of vimentin, calponin and HHF-35 was applied to 28 salivary gland tumors. The results demonstrated a higher percent sensitivity of vimentin and calponin compared to HHF-35. However, calponin and HHF-35 presented a focal labeling pattern in contrast with the diffuse distribution of vimentin. The cells predominantly stained by all tested antibodies included nonluminal cells in duct-like and tubular structures, such as those seen in pleomorphic adenomas and adenoid cystic carcinomas, as well as cells in the cords and nests of polymorphous low-grade adenocarcinomas and peripheral cells of sheets and nests of myoepitheliomas. In conclusion, the combination of calponin and vimentin is suggested for the identification of myoepithelial cells in salivary gland tumors.

Terminal duct adenocarcinomas of the parotid gland

1995 ◽  
Vol 109 (5) ◽  
pp. 466-468 ◽  
Author(s):  
Bonnie L. Kemp ◽  
John G. Batsakis ◽  
Adel K. El-Naggar ◽  
Sophia N. Kotliar ◽  
Mario A. Luna
Keyword(s):  
Salivary Gland ◽  
Parotid Gland ◽  
Salivary Glands ◽  
Minor Salivary Gland ◽  
Low Grade ◽  
Minor Salivary Glands ◽  
Biological Behaviour ◽  
Parotid Neoplasms ◽  
Clinicopathological Study

AbstractThe major salivary glands are considered to rarely be the sites of primary terminal duct adenocarcinomas, a neoplasm with a considerable predilection for origin from intraoral minor salivary glands. We present a clinicopathological study of 22 terminal duct adenocarcinomas of the parotid gland, the largest single series to date. A comparison between the parotid neoplasms and over 200 minor salivary gland terminal duct adenocarcinomas indicates there is little difference in biological behaviour and confirms the low-grade quality of the carcinomas, regardless of site of origin.

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