Publications by authors named "Darielys Santana Mederos"

8 Publications

  • Page 1 of 1

Glycan Array Evaluation of Synthetic Epitopes between the Capsular Polysaccharides from 19F and 19A.

ACS Chem Biol 2021 09 1;16(9):1671-1679. Epub 2021 Sep 1.

Department of Medical Biotechnology and Translational Medicine, University of Milan, Via Saldini 50, 20133 Milano, Italy.

Vaccination represents the most effective way to prevent invasive pneumococcal diseases. The glycoconjugate vaccines licensed so far are obtained from capsular polysaccharides (CPSs) of the most virulent serotypes. Protection is largely limited to the specific vaccine serotypes, and the continuous need for broader coverage to control the outbreak of emerging serotypes is pushing the development of new vaccine candidates. Indeed, the development of efficacious vaccine formulation is complicated by the high number of bacterial serotypes with different CPSs. In this context, to simplify vaccine composition, we propose the design of new saccharide fragments containing chemical structures shared by different serotypes as cross-reactive and potentially cross-protective common antigens. In particular, we focused on (Sp) 19A and 19F. The CPS repeating units of Sp 19F and 19A are very similar and share a common structure, the disaccharide ManNAc-β-(1→4)-Glc (A-B). Herein, we describe the synthesis of a small library of compounds containing different combinations of the common 19F/19A disaccharide. The six new compounds were tested with a glycan array to evaluate their recognition by antibodies in reference group 19 antisera and factor reference antisera (reacting against 19F or 19A). The disaccharide A-B, phosphorylated at the upstream end, emerged as a hit from the glycan array screening because it is strongly recognized by the group 19 antisera and by the 19F and 19A factor antisera, with similar intensity compared with the CPSs used as controls. Our data give a strong indication that the phosphorylated disaccharide A-B can be considered a common epitope among different Sp 19 serotypes.
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http://dx.doi.org/10.1021/acschembio.1c00347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453487PMC
September 2021

SARS-CoV-2 RBD-Tetanus Toxoid Conjugate Vaccine Induces a Strong Neutralizing Immunity in Preclinical Studies.

ACS Chem Biol 2021 07 4;16(7):1223-1233. Epub 2021 Jul 4.

Center for Genetic Engineering and Biotechnology, Ave 31 e/158 y 190, Havana 10600, Cuba.

Controlling the global COVID-19 pandemic depends, among other measures, on developing preventive vaccines at an unprecedented pace. Vaccines approved for use and those in development intend to elicit neutralizing antibodies to block viral sites binding to the host's cellular receptors. Virus infection is mediated by the spike glycoprotein trimer on the virion surface via its receptor binding domain (RBD). Antibody response to this domain is an important outcome of immunization and correlates well with viral neutralization. Here, we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid (TT) induce a potent immune response in laboratory animals. Some advantages of immunization with RBD-TT conjugates include a predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. These result demonstrate the potential of the conjugate COVID-19 vaccine candidates and enable their advance to clinical evaluation under the name SOBERANA02, paving the way for other antiviral conjugate vaccines.
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http://dx.doi.org/10.1021/acschembio.1c00272DOI Listing
July 2021

Molecular Aspects Concerning the Use of the SARS-CoV-2 Receptor Binding Domain as a Target for Preventive Vaccines.

ACS Cent Sci 2021 May 19;7(5):757-767. Epub 2021 Apr 19.

Finlay Vaccine Institute, 200 and 21 Street, Havana 11600, Cuba.

The development of recombinant COVID-19 vaccines has resulted from scientific progress made at an unprecedented speed during 2020. The recombinant spike glycoprotein monomer, its trimer, and its recombinant receptor-binding domain (RBD) induce a potent anti-RBD neutralizing antibody response in animals. In COVID-19 convalescent sera, there is a good correlation between the antibody response and potent neutralization. In this review, we summarize with a critical view the molecular aspects associated with the interaction of SARS-CoV-2 RBD with its receptor in human cells, the angiotensin-converting enzyme 2 (ACE2), the epitopes involved in the neutralizing activity, and the impact of virus mutations thereof. Recent trends in RBD-based vaccines are analyzed, providing detailed insights into the role of antigen display and multivalence in the immune response of vaccines under development.
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http://dx.doi.org/10.1021/acscentsci.1c00216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084267PMC
May 2021

Expanding the Scope of Ugi Multicomponent Bioconjugation to Produce Pneumococcal Multivalent Glycoconjugates as Vaccine Candidates.

Bioconjug Chem 2020 09 2;31(9):2231-2240. Epub 2020 Sep 2.

Center for Natural Products Research, Faculty of Chemistry, University of Havana, Zapata y G, Havana 10400, Cuba.

Conjugate vaccines against encapsulated pathogens like face many challenges, including the existence of multiple serotypes with a diverse global distribution that constantly requires new formulations and higher coverage. Multivalency is usually achieved by combining capsular polysaccharide-protein conjugates from invasive serotypes, and for , this has evolved from 7- up to 20-valent vaccines. These glycoconjugate formulations often contain high concentrations of carrier proteins, which may negatively affect glycoconjugate immune response. This work broadens the scope of an efficient multicomponent strategy, leading to multivalent pneumococcal glycoconjugates assembled in a single synthetic operation. The bioconjugation method, based on the Ugi four-component reaction, enables the one-pot incorporation of two different polysaccharide antigens to a tetanus toxoid carrier, thus representing the fastest approach to achieve multivalency. The reported glycoconjugates incorporate three combinations of capsular polysaccharides 1, 6B, 14, and 18C from . The glycoconjugates were able to elicit functional specific antibodies against pneumococcal strains comparable to those shown by mixtures of the two monovalent glycoconjugates.
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http://dx.doi.org/10.1021/acs.bioconjchem.0c00423DOI Listing
September 2020

Design and Biological Assembly of Polyester Beads Displaying Pneumococcal Antigens as Particulate Vaccine.

ACS Biomater Sci Eng 2018 Sep 14;4(9):3413-3424. Epub 2018 Aug 14.

Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan Campus, Nathan, Queensland 4111, Australia.

can cause life-threatening infections mostly in infants, children, and elderly people. Capsular polysaccharide conjugate vaccines provide serotype-dependent protection against infections but fail to protect against new emerging serotypes. To overcome these limitations, pneumolysin (Ply), a serotype-independent and conserved protein was selected. As such subunit vaccines lack immunogenicity, we engineered Ply to be attached to self-assembled polyester beads in order to boost immunogenicity. To display Ply at the surface of these polyester beads, it was translationally fused to the N-terminus of the polyhydroxybutyrate (PHB) synthase (PhaC), which mediates PHB bead assembly inside recombinant . We also chemically conjugated the capsular polysaccharide (CPS) 19F to isolated PHB beads to further assess their antigen carrier properties. CPS conjugated to soluble tetanus toxoid served as control. Balb/c mice immunized with Ply-PhaC beads and 19F-PhaC beads induced specific and higher IgG levels than the respective soluble counterparts. The induced IgG antibodies recognized Ply in whole cell lysates of six different serotypes of Additionally, restimulated splenocytes from animals immunized with Ply-PhaC beads produced a balanced INF-γ/IL-17A profile unlike animals immunized with soluble Ply. The 19F-PhaC beads induced production of antibodies showing high opsonophagocytic titers against the homologous strain, serotype 19F, while CPS 19F only mixed with PhaC beads did not elicit any detectable immune response. This study provided insight into the design of PHB beads as a carrier of proteinaceous antigens and CPS in order to induce immune responses for the prevention of pneumococcal infections.
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http://dx.doi.org/10.1021/acsbiomaterials.8b00579DOI Listing
September 2018

Safety and immunogenicity of the Cuban heptavalent pneumococcal conjugate vaccine in healthy infants. Results from a double-blind randomized control trial Phase I.

Vaccine 2018 08 10;36(32 Pt B):4944-4951. Epub 2018 Jul 10.

Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba. Electronic address:

Background: Cuba has a new pneumococcal conjugate vaccine candidate (PCV7-TT). This study evaluates the safety and immunogenicity in healthy infants using 2p+1 vaccination schedule.

Methods: A phase I, controlled, randomized and double blind clinical trial was designed. 30 unvaccinated healthy infants were included. 20 subjects were assigned to study group (PCV7-TT) and 10 to control group (Synflorix®) to receive the vaccines at 7, 8 months of age (primary series) and 11 months (booster dose). Blood samples were collected 30 days after second dose and post booster for antibodies measure analysis by ELISA and OPA. The statistics analysis included the frequency of occurrence for adverse events and the immune response. Non-parametric tests were used to compare the immune response. The clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173 available at http://registroclinico.sld.cu.

Results: Overall, the safety profile of PCV7-TT was similar to Synflorix®. Local reactions were predominant and systemic events were mild in severity. Swelling and redness were frequently associated with PCV7-TT mainly after the first dose (50% and 40% respectively). 15% and 10% of subject reported severe swelling after first dose with PCV7-TT and after second dose with Synflorix®. Mild fever (≥38-≤39), vomiting and sleep disturb were the systemic events reported. 100% of infants achieved pneumococcal IgG antibody concentrations ≥0.35 µg/ml after booster dose for serotypes 1, 14, 18C and 19F in each vaccine group. For serotypes 5, 6B and 23F, more than 80% infants vaccinated with Synflorix® or PCV7-TT achieved protective IgG GMC ≥ 0.35 µg/ml after booster dose. OPA proportion's responders to the seven common serotypes were 89.5% or more after the primary dose and 100% after booster dose in vaccinated with PCV7-TT.

Conclusions: The Cuban PCV7-TT is safe, well tolerated and immunogenic in healthy infants.
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http://dx.doi.org/10.1016/j.vaccine.2018.05.027DOI Listing
August 2018

From individual to herd protection with pneumococcal vaccines: the contribution of the Cuban pneumococcal conjugate vaccine implementation strategy.

Int J Infect Dis 2017 Jul 28;60:98-102. Epub 2017 Apr 28.

Finlay Vaccine Institute, Havana, Cuba.

A new pneumococcal conjugate vaccine is currently undergoing advanced clinical evaluation prior to its planned introduction in Cuba. The implementation of the pneumococcal vaccination strategy has been designed with consideration of the need to maximize both its direct and indirect effects. A novel approach is suggested, which addresses preschool children as the first-line target group to generate herd immunity in infants and to have an impact on transmission at the community level. The clinical evaluation pipeline is described herein, including evaluations of effectiveness, cost-effectiveness, and impact. The scientific contribution of the Cuban strategy could support a paradigm shift from individual protection to a population effect based on a rigorous body of scientific evidence.
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http://dx.doi.org/10.1016/j.ijid.2017.03.011DOI Listing
July 2017

Prevalence of Pneumococcal Nasopharyngeal Carriage Among Children 2-18 Months of Age: Baseline Study Pre Introduction of Pneumococcal Vaccination in Cuba.

Pediatr Infect Dis J 2017 01;36(1):e22-e28

From the *Tropical Medicine Institute "Pedro Kourí" (IPK), Havana, Cuba; †Pediatric Hospital "Paquito González Cueto," Cienfuegos, Cuba; ‡Finlay Vaccine Institute, Havana, Cuba; and §Medical University of Cienfuegos, Cienfuegos, Cuba.

Background: A new vaccine candidate against pneumococcus is being developed in Cuba, and it is a priority of the national health system. There is limited information on nasopharyngeal colonization burden, though it is essential for monitoring the impact of the vaccine. The study aims to estimate the prevalence of nasopharyngeal colonization in children 2-18 months of age and identify circulating serotypes, antimicrobial resistance and its association with selected risk factors.

Methods: A cross-sectional study was conducted between October and December 2013 in Cienfuegos municipality. Inclusion criteria were evaluated, and informed consent was obtained from the parents. Clinical and epidemiologic data were collected through a semistructured questionnaire. Nasopharyngeal swabs according to established protocols were taken. Data analysis included frequency distributions and comparison of proportions. The association between colonization and selected risk factors was assessed by multivariate analysis.

Results: A total of 984 children (87.2% living in urban areas) were included. The overall prevalence of colonization was 21.6%. The most frequent serotypes isolated were 6A (23.1%), 23F (10.8%), 6B (10.3%), 19F (8.5%) and 14 (3.3%). We found no resistance to β-lactamases in circulating serotypes. Living with sibling younger than 5 years, previous respiratory infections, previous hospitalization and day-care attendance were determinants of nasopharyngeal carriage.

Conclusions: The findings suggest that the burden of pneumococcal disease and colonization in Cuba could be significantly affected after vaccine introduction.
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http://dx.doi.org/10.1097/INF.0000000000001341DOI Listing
January 2017
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