Vol 4-4 Research Article

Diagnostic and Prognostic value of Immunohistochemistry in Destructive Paediatric Maxillary Pathologies

Priya Jeyaraj

Commanding Officer, Military Dental Centre (Gough Lines), Secunderabad, Telangana, Pin- 500015, India

Introduction: Establishing an accurate diagnosis and probable prognosis of ambiguous, extensive and destructive maxillary pathologies, is imperative for an appropriate, timely and effective treatment modality to be instituted. This is particularly true in the paediatric population, in order to ensure complete elimination of the lesion, with the least possible morbidity, debility, or interference with normal jaw growth.

Objectives: To assess the diagnostic and prognostic value of Immunohistochemistry (IHC) as an adjunct to Histopathological examination (HPE), in cases of destructive paediatric maxillary pathologies. To use the information thus obtained, to select the most ideal and efficacious management protocol for each case.

Material & Methods: An extensive study was carried out on 25 cases of destructive (as evidenced clinically and radiographically) maxillary lesions, in children of ages between 5 and 16 years. Positivity for an IHC tumor marker, namely Calretinin, was employed to distinguish maxillary cysts from tumors. In addition, Labelling indices of two IHC cell proliferation markers, namely Ki-67 and PCNA, indicated the proliferative activity of constituent cells of the pathologies, which aided in predicting their aggressive nature and recurrence potential. On the basis of the above information, the choice between a conservative versus radical treatment approach was made for each individual case.

Results & Conclusion: IHC proved to be of immense value as a diagnostic marker and a prognostic indicator in the paediatric maxillary pathologies. In addition to aiding the pathologist in making an accurate confirmatory diagnosis, it also served as an invaluable tool to the surgeon, in guiding the treatment plan by indicating the likely prognosis and chances of recurrence of these lesions.

DOI: 10.29245/2578-3009/2020/4.1192 View / Download Pdf
Vol 4-4 Mini Review

Implantable vaccines: a solution for immune system manipulation to any antigenic stimulus

Ioanna Zerva, Vasileia Pateraki, Irene Athanassakis*

Department of Biology, University of Crete, Vassilika Vouton, Heraklion 70013, Crete, Greece

Effective and side-effect-free vaccines are still difficult tasks to achieve for a great majority of antigenic stimuli. Pathogen manipulation to abort infectivity and antigen delivery to ensure immune responsiveness are the major components vaccine technology tries to resolve. However, the development of an immune response is still a complicated matter, lies on hundreds of parameters and any effort towards activation can easily lead to adverse effects, making immunotherapy very difficult to control. The present review attempts to highlight the major parameters affecting immune responsiveness and show that vaccine technology, except from pathogen manipulation and the development of antigen delivery systems, requires attention to additional check-points. Analyzing the recently described personalized implantable vaccine technology, it becomes obvious that the nature of each antigenic stimulus dictates different responsiveness to the organism, which discourages the use of universal adjuvant and antigen-delivery systems. On the contrary, the ex vivo tuning of the immune response proposed by the implantable vaccine technology, allows controllable amendment of the response. The development of personalized technologies is expected to provide valuable tools for the management of human pathology.

DOI: 10.29245/2578-3009/2020/4.1193 View / Download Pdf
Vol 4-4 Commentary

Commentary: COVID-19 and the Path to Immunity

Lisa M. James1,2,3,4, Effie-Photini C. Tsilibary1,2, Spyros Charonis1,2, Apostolos P. Georgopoulos1,2,3,4*

1 Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN, USA

2 Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA

3 Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA

4 Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, USA

DOI: 10.29245/2578-3009/2020/4.1201 View / Download Pdf
Vol 4-4 Original Research Article

Comparison of Pneumococcal Avidity and Antibody Concentration in Children with Recurrent Infections: A Retrospective Pilot Study

Sara B. Intner1, Michelle Altrich2, Niraj C. Patel1

1Department of Pediatrics, Levine Children’s Hospital, Atrium Health, Charlotte, NC, USA

2Viracor Eurofins, Lee’s Summit, MO, USA

Measurement of pneumococcal antibody concentration is a frequently used parameter for functional antibody response to vaccination. Antibody concentration in response to vaccination and strength of antigen-antibody (avidity) interaction are both important measurements of functional antibody response. Both antibody concentration and avidity contribute to immunity against invasive pneumococcal disease. Higher avidity is correlated with increasing bactericidal activity and opsonophagocytosis. On the other hand, patients with lower pneumococcal avidity may be more likely to develop clinically significant pneumococcal sinopulmonary infections. Nine patients with recurrent bacterial respiratory infections were identified by retrospective chart review as having adequate pneumococcal antibody concentrations, but with low avidity for multiple serotypes following immunization with pneumococcal vaccine polyvalent (PPSV23). We assessed response with IgG replacement therapy in these patients. The mean number of serotypes with a normal antibody response (>1.3 𝛍g/ml) among 9 children following immunization with pneumococcal vaccine polyvalent was 19.1 (range 12-22) of 23 serotypes while the mean number of serotypes with a normal avidity response (≥1.0) was 4.7 (range 2-7) of 23 serotypes. Flow cytometry was performed for 8 of the 9 patients prior to starting SCIG replacement therapy. 100% of the cohort experienced a significant decrease in yearly infection rate after starting immunoglobulin replacement. This is the first study to assess the clinical response to immune globulin replacement in patients with normal pneumococcal antibody response but poor pneumococcal avidity, and suggests that patients with poor pneumococcal avidity but apparent normal response by pneumococcal antibody following PPSV23 may benefit from IgG replacement therapy.

DOI: 10.29245/2578-3009/2020/4.1194 View / Download Pdf
Vol 4-4 Original Research Article

Heterologous Protection to COVID-19 with BCG Vaccine: Deciphering the Reality Using Meta-Analysis Approach

Anurag Singh1, Lakshya Gupta2, Vandana Gupta1*

1Department of Microbiology, Ram Lal Anand College, University of Delhi, Benito Juarez Road, New Delhi 110021, India

2Department of Computer Science and Engineering, Indian Institute of Technology, Varanasi, Uttar Pradesh 221005, India

The coronavirus disease (COVID-19) emerged in China in December 2019 and has since spread to over 188 countries affecting millions of individuals. Several reports in favour or against the heterologous protection conferred by the BCG vaccine against COVID-19 came up in the initial days of the pandemic and continue to do so. In this study, we compared the three worst-affected nations: The USA, India, and Brazil, their current pandemic scenario, and their respective national BCG immunization policies. USA recommends BCG vaccine only to a specific group of people and never had a national immunization scheme in place. Meanwhile, India introduced a nationwide scheme as early as 1948 and continues to endorse BCG immunization at birth. Brazil used the oral route to administer the BCG vaccine till 1976, and then shifted to intradermal injection. The correlation coefficient for the total number of cases, cases per million, the total number of deaths, deaths per million and case fatality rate ranges between 0.81-0.98. This indicates a very strong positive correlation in the various epidemiological parameters between countries with no national immunization scheme (USA) and countries with stringent national policies on BCG vaccination. The strongest correlation exists between the USA and Brazil followed by Brazil and India which is very closely followed by the USA and India. We found no consistent evidence to infer in favour of the hypothesis that BCG provides any non-specific protection against COVID-19.

BCG: Bacillus Calmette-Guérin

COVID-19: Coronavirus Disease 2019

DPT: Diphtheria, Pertussis, and Tetanus

HPV: Human Papillomavirus

HSV: Herpes Simplex Virus

ICTV: International Committee on Taxonomy of Viruses

OPV: Oral Poliovirus Vaccine

RSV: Respiratory Syncytial Virus

SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2

TB: Tuberculosis

WHO: World Health Organization

DOI: 10.29245/2578-3009/2020/4.1199 View / Download Pdf
Vol 4-4 Original Research Article

SARS-CoV-2 Virus and Human Leukocyte Antigen (HLA) Class II: Investigation in silico of Binding Affinities for COVID-19 Protection and Vaccine Development

Spyros S. Charonis 1,2, Effie-Photini Tsilibary 1,2, Apostolos P. Georgopoulos 1,2*

1Brain Sciences Center, Department of Veterans Affairs Health Care System, Minneapolis, MN 55417, USA

2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN 55455, USA

SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Human Leukocyte Antigen (HLA) Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common HLA-Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each HLA allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a HLA Class II molecule for CD4+ T cell activation by the antigen-HLA molecule complex.

DOI: 10.29245/2578-3009/2020/4.1198 View / Download Pdf
Vol 4-4 Original Research Article

Is Rotavirus Immunization Safe in Infants Born to Mothers Treated with Immunosuppressive Drugs for Inflammatory Bowel Disease During Pregnancy?

R. Christina Smith, MD1, Meera N. Patel2, Richard Sigmon, MD3, Niraj C. Patel, MD, MS1

1Division of Pediatrics, Division of Pediatric Infectious Disease and Immunology, Atrium Health, Charlotte, NC, USA

2North Carolina School of Science and Math

3Department of Internal Medicine, Division of Gastroenterology, Atrium Health, Charlotte, NC, USA

The licensed rotavirus vaccines are live attenuated and are a component of the routine U.S. childhood immunization schedule. Live vaccines administered to infants of mothers who received biologic response modifiers (BRM) during pregnancy can potentially cause serious vaccine-associated disease. The Advisory Committee on Immunization Practices (ACIP) recommends infants born to women who received BRM during pregnancy avoid live viral vaccines during the first year of life. There is a paucity of information regarding adverse events following inadvertent administration of live viral vaccines in these infants. We report three infants, born to mothers receiving infliximab during pregnancy, who tolerated multiple doses of rotavirus vaccine. Live viral vaccines may be safe in infants who were exposed to BRM in utero. Further studies are needed to support this observation, as this could affect current ACIP recommendations.

DOI: 10.29245/2578-3009/2020/4.1195 View / Download Pdf
Vol 4-4 Mini Review Article

Autophagy Modulation in Mammarenavirus Infection

Giovanna L. Gallo1*, Julieta S. Roldán2, Laura R. Delgui3,4

1Centro de Virología Animal (CEVAN)-CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas).

2Instituto de Investigaciones Biotecnológicas "Dr. Rodolfo A. Ugalde" (IIBIO), Universidad Nacional de San Martín (UNSAM) - CONICET, San Martín, Buenos Aires, Argentina.

3Instituto de Histología y Embriología de Mendoza (IHEM-CONICET). Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, CONICET, Mendoza, Argentina.

4Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo, Mendoza, Argentina.

Mammarenavirus genus groups viruses causing human haemorrhagic diseases, including the New World (NW) Junín virus (JUNV), and the Old World (OW) viruses Lassa (LASV), among others. The high mortality and morbidity rates associated to pathogenic mammarenaviruses, the absence of vaccines and the constant threat of new emerging species, make these viruses a public health concern in endemic areas. Autophagy is a widely-known intracellular metabolic pathway involved in maintaining the cellular homeostasis in response to several stress conditions.

DOI: 10.29245/2578-3009/2020/4.1197 View / Download Pdf