The Impact of Bioinformatics on Vaccine Design and Development

Vaccines are the pharmaceutical products that offer the best cost‐benefit ratio in the prevention or treatment of diseases. In that a vaccine is a pharmaceutical product, vaccine development and production are costly and it takes years for this to be accomplished. Several approaches have been applied to reduce the times and costs of vaccine development, mainly focusing on the selection of appropriate antigens or antigenic structures, carriers, and adjuvants. One of these approaches is the incorporation of bioinformatics methods and analyses into vaccine development. This chapter provides an overview of the application of bioinformatics strategies in vaccine design and development, supplying some successful examples of vaccines in which bioinformatics has furnished a cutting edge in their development. Reverse vaccinology, immunoinformatics, and structural vaccinology are described and addressed in the design and development of specific vaccines against infectious diseases caused by bacteria, viruses, and parasites. These include some emerging or re‐emerging infectious diseases, as well as therapeutic vaccines to fight cancer, allergies, and substance abuse, which have been facilitated and improved by using bioinformatics tools or which are under development based on bioinformatics strategies

Vaccination against Trichinella spiralis: Potential, Limitations and Future Directions

Trichinellosis is a food-borne parasitic disease caused by round worms of the genus Trichinella. The majority of human outbreaks are attributed to consumption of raw or undercooked pork meat contaminated with T. spiralis muscle larvae. A blocking-transmission vaccine against trichinellosis will allow preventing swine infection and will contribute to disease control. In this chapter, different vaccine candidates so far developed against T. spiralis, including first-, second-, and third-generation vaccines, are discussed. Most vaccine candidates are based on a unique antigen mainly from the muscle larva stage, inducing with some exceptions, partial protection although a mix Th1/Th2 immune response is elicited. Therefore, the need for identification of new antigens from different parasite stages focusing on infective intestinal larvae, adult, and newborn larvae stages as well as the evaluation of their protective capacity in pigs is presented. The design of multi-epitope vaccines and the use of adjuvants or immunomodulatory molecules capable to polarize the immune response to a Th2-type-protective response are discussed as imperative elements of modern vaccines. Plant-based vaccines and probiotics as excellent tools for vaccine development against T. spiralis are also presented as an attractive platform for veterinary vaccines

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Detection of Myosin 1g Overexpression in Pediatric Leukemia by Novel Monoclonal Antibodies

Myosin 1g (Myo1g) is a mechanoenzyme associated with actin filaments, expressed exclusively in hematopoietic cells, and involved in various cellular functions, including cell migration, adhesion, and membrane trafficking. Despite the importance of Myo1g in distinct functions, there is currently no monoclonal antibody (mAb) against Myo1g. mAbs are helpful tools for the detection of specific antigens in tumor cells and other tissues. The development of mAbs against targeted dysregulated molecules in cancer cells remains a crucial tool for aiding in the diagnosis and the treatment of patients. Using hybridoma technology, we generated a panel of hybridomas specific for Myo1g. ELISA, immunofluorescence, and Western blot assay results revealed the recognition of Myo1g by these novel monoclonal antibodies in normal and transformed T and B cells. Here, we report the development and application of new monoclonal antibodies against Myo1g for their potential use to detect its overexpression in acute lymphoblastic leukemia (ALL) patients

Detection of Myosin 1g Overexpression in Pediatric Leukemia by Novel Monoclonal Antibodies

Myosin 1g (Myo1g) is a mechanoenzyme associated with actin filaments, expressed exclusively in hematopoietic cells, and involved in various cellular functions, including cell migration, adhesion, and membrane trafficking. Despite the importance of Myo1g in distinct functions, there is currently no monoclonal antibody (mAb) against Myo1g. mAbs are helpful tools for the detection of specific antigens in tumor cells and other tissues. The development of mAbs against targeted dysregulated molecules in cancer cells remains a crucial tool for aiding in the diagnosis and the treatment of patients. Using hybridoma technology, we generated a panel of hybridomas specific for Myo1g. ELISA, immunofluorescence, and Western blot assay results revealed the recognition of Myo1g by these novel monoclonal antibodies in normal and transformed T and B cells. Here, we report the development and application of new monoclonal antibodies against Myo1g for their potential use to detect its overexpression in acute lymphoblastic leukemia (ALL) patients

Premio "BIOMERIUX"

XLII Congreso Mexicano de Patología Clínica y el XXI Congreso Latinoamericano de Patología Clínica, otorgó una Constancia a: AE Martínez Fernández; MS Méndez Tovar; RM Ribas Jaimes; RM Ribas Aparicio, JE Donis Rocandio por la presentación del trabajo libre: Detección Fenotópica y Genotípica de Metalo-B-Lactamasas en Cepas de Pseudomonas Aeruginosa Cepas de Multidrogorresistente; llevado a cabo del 24 al 27 de Octubre del 2012 en Cancún Center, Cancún Quintana Roo

Identification of Novel Potential Vaccine Candidates against Tuberculosis Based on Reverse Vaccinology

Tuberculosis (TB) is a chronic infectious disease, considered as the second leading cause of death worldwide, caused by Mycobacterium tuberculosis. The limited efficacy of the bacillus Calmette-Guérin (BCG) vaccine against pulmonary TB and the emergence of multidrug-resistant TB warrants the need for more efficacious vaccines. Reverse vaccinology uses the entire proteome of a pathogen to select the best vaccine antigens by in silico approaches. M. tuberculosis H37Rv proteome was analyzed with NERVE (New Enhanced Reverse Vaccinology Environment) prediction software to identify potential vaccine targets; these 331 proteins were further analyzed with VaxiJen for the determination of their antigenicity value. Only candidates with values ≥0.5 of antigenicity and 50% of adhesin probability and without homology with human proteins or transmembrane regions were selected, resulting in 73 antigens. These proteins were grouped by families in seven groups and analyzed by amino acid sequence alignments, selecting 16 representative proteins. For each candidate, a search of the literature and protein analysis with different bioinformatics tools, as well as a simulation of the immune response, was conducted. Finally, we selected six novel vaccine candidates, EsxL, PE26, PPE65, PE_PGRS49, PBP1, and Erp, from M. tuberculosis that can be used to improve or design new TB vaccines

Cambiando los paradigmas de la infección por M. pneumoniae en pediatría

La neumonía atípica es un término que originalmente se utilizó en pacientes adultos que presentaban neumonías de curso atípico, generalmente leves y de evolución benigna, que eran causadas por agentes como: Mycoplasma pneumoniae, Chlamydophila pneumoniae y Legionella pneumophila. En población pediátrica la presentación, tanto clínica como epidemiológica, de las neumonías por M. pneumoniae merece una especial atención ya que no siempre son cursos benignos y pueden existir numerosos cuadros extrapulmonares asociados; el proceso diagnóstico es complejo y poco diferencial de otros agentes etiológicos. Recientemente ha llamado la atención la emergencia de la resistencia a macrólidos en algunos países del mundo, por lo que existen controversias respecto al tratamiento. Estudios numerosos realizados a nivel mundial, particularmente derivados de países asiáticos, han generado nueva información en relación al comportamiento biológico, clínico, epidemiológico, radiológico y respuesta terapéutica de M. pneumoniae en pacientes pediátricos

1er. lugar en el "Primer reporte en Latinoamérica de la rRNA metiltransferasa ArmA en una cepa de Acinetobacter baumanni de origen nosocomial"

En la 3ra. Reunión Regional y 1er. Congreso Latinoaméricano de Ciencias Microbiológicas; el Tecnológico de Monterrey campus Puebla y la Asociación Poblana de Ciencias Microbiológicas A.C. otorgó una Constancia a Ribas Aparicio Rosa María; Martínez Hernández Johana Vianey; Cauich Sánchez Patricia Isidra; Donis Rocandio Jenny Elizabeth y Aparicio Ozores Gerardo por obtener el 1er. lugar en la presentación del trabajo: "Primer reporte en Latinoámerica de la rRNA metiltransferas ArmA en una cepa de Acinetobacter baumanni de origen nosocomial" en la modalidad CARTELES celebrado en la Cd. de México los días 11 y 12 de Noviembre del 2011