Publications by authors named "Dagmar García Rivera"

19 Publications

  • Page 1 of 1

Effect of Biomodulina-T® and VA-MENGOC-BC® on lymphocyte subpopulations in older adults.

Exp Gerontol 2021 10 26;153:111497. Epub 2021 Jul 26.

Institute of Hematology and Immunology, Immunochemistry-Immunology Department, 19th St, between 8th and 10th St, Vedado, 10400 Plaza de la Revolución, Havana, Cuba. Electronic address:

Introduction: The elderly population suffers from the natural process called immunosenescence, which may be related to the high mortality rates it has against the SARS-CoV2 virus, which is why therapies that improve the immune status are required. The combined treatment of the VA-MENGOC-BC® (V-BC) vaccine and the Biomodulina T® (BT) drug could achieve this purpose. This treatment could immunomodulate both the innate and adaptive branches of the immune system simultaneously.

Objective: To determine the effect of BT and V-BC on the immunomodulation of lymphocyte subpopulations in older adults.

Methods: Our study was carried out in 30 apparently healthy Cuban adults over 65 years of age. The study included three groups of 10 subjects per treatment: a combination of both and the monotherapies. Before and 7 days after treatment, 2 mL of peripheral blood was drawn from each subject. Multiparametric flow cytometry was used to identify lymphocyte subpopulations. For the comparison between the groups, point estimates and the confidence intervals of the Odds Ratio were made.

Results: We found that subpopulations of B lymphocytes and natural cytotoxic T (NKT) cells increased only with the administration of BT. Additionally, combination treatments and V-BC did not generate statistically significant immunomodulatory changes in any of the studied lymphocyte subpopulations.

Conclusions: BT presented an immunoenhancing effect on the B and NKT lymphocyte subpopulations of older adults. The three-dose treatment scheme a novel and specific treatment strategy for this formulation. We also were verified that the combined application of V-BC and BT did not have the expected benefits. All these findings suggest that BT administration is a promising approach for immune restoration and to offering protection in elderly patients against COVID-19.
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http://dx.doi.org/10.1016/j.exger.2021.111497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310781PMC
October 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

Repeat-Dose Toxicity Study Using the AFPL1-Conjugate Nicotine Vaccine in Male Sprague Dawley Rats.

Pharmaceutics 2019 Nov 23;11(12). Epub 2019 Nov 23.

Health Sciences North Research Institute (HSNRI), Sudbury, ON P3E 2H3, Canada.

Tobacco smoking is the cause of 20% of Canadian deaths per year. Nicotine vaccines present a promising alternative to traditional smoking cessation products, but to date, no vaccine has been able to move through all phases of clinical trials. We have previously demonstrated that the AFPL1-conjugate nicotine vaccine does not induce systemic or immunotoxicity in a mouse model and that a heterologous vaccination approach is more advantageous than the homologous routes to inducing mucosal and systemic anti-nicotine antibodies. The purpose of this study was to confirm the safety profile of the vaccine in a repeat-dose toxicity study. The heterologous vaccination strategy was again used, and Sprague Dawley rats were administered a dose five times greater than in our previous studies. Physiological conditions, food and water consumption, body temperature, injection site inflammation, relative weights of organs, histopathology, and blood chemistry and hematology were evaluated during the course of the vaccination period to determine the safety of the vaccine. The AFPL1-conjugate nicotine vaccine did not induce clinically relevant changes or induce symptoms that would be associated with toxicity, making it a promising candidate for future investigations.
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http://dx.doi.org/10.3390/pharmaceutics11120626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955701PMC
November 2019

Assessing the immunogenicity and toxicity of the AFPL1-conjugate nicotine vaccine using heterologous and homologous vaccination routes.

PLoS One 2019 23;14(8):e0221708. Epub 2019 Aug 23.

Health Sciences North Research Institute, Sudbury, Ontario, Canada.

Despite the increased risks of cancers and cardiovascular related diseases, tobacco smoking continues to be prevalent in the population due largely in part to the addictive nature of nicotine. Nicotine vaccines are an attractive alternative to the current smoking cessation options but have yet to be successful enough in clinical trials to reach the market due to a lack of neutralizing antibodies and inconsistent results. Using AFPL1 derived from the Cuban meningococcal vaccine as an adjuvant, we have previously published promising results with an intranasally administered nicotine vaccine. In order to examine the immunogenicity and safety of this vaccine in mice we set up a pilot trial administering the vaccine either intranasally, intramuscularly or utilizing both routes simultaneously and evaluated immune responses and clinical symptoms throughout the duration of the vaccination protocol and post-mortem. These data further demonstrate the ability of the AFPL1 nicotine conjugate vaccine to be a safe and potential candidate for clinical use.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221708PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707630PMC
March 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

Multicomponent polysaccharide-protein bioconjugation in the development of antibacterial glycoconjugate vaccine candidates.

Chem Sci 2018 Mar 19;9(9):2581-2588. Epub 2018 Jan 19.

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

A new synthetic strategy for the development of multivalent antibacterial glycoconjugate vaccines is described. The approach comprises the utilization of an isocyanide-based multicomponent process for the conjugation of functionalized capsular polysaccharides of and Typhi to carrier proteins such as diphtheria and tetanus toxoids. For the first time, oxo- and carboxylic acid-functionalized polysaccharides could be either independently or simultaneously conjugated to immunogenic proteins by means of the Ugi-multicomponent reaction, thus leading to mono- or multivalent unimolecular glycoconjugates as vaccine candidates. Despite the high molecular weight of the two or three reacting biomolecules, the multicomponent bioconjugation proved highly efficient and reproducible. The Ugi-derived glycoconjugates showed notable antigenicity and elicited good titers of functional specific antibodies. To our knowledge, this is the only bioconjugation method that enables the incorporation of two different polysaccharidic antigens to a carrier protein in a single step. Applications in the field of self-adjuvanting, eventually anticancer, multicomponent vaccines are foreseeable.
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http://dx.doi.org/10.1039/c7sc05467jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5897956PMC
March 2018

Bioengineered polyester beads co-displaying protein and carbohydrate-based antigens induce protective immunity against bacterial infection.

Sci Rep 2018 01 30;8(1):1888. Epub 2018 Jan 30.

Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.

The efficacy of protein and carbohydrate antigens as vaccines can be improved via particulate delivery strategies. Here, protein and carbohydrate antigens used in formulations of vaccines against Neisseria menigitidis were displayed on in vivo assembled polyester beads using a combined bioengineering and conjugation approach. An endotoxin-free mutant of Escherichia coli was engineered to produce translational fusions of antigens (Neisseria adhesin A (NadA) and factor H binding protein (fHbp) derived from serogroup B) to the polyhydroxybutyrate synthase (PhaC), in order to intracellularly assemble polyester beads displaying the respective antigens. Purified beads displaying NadA showed enhanced immunogenicity compared to soluble NadA. Both soluble and particulate NadA elicited functional antibodies with bactericidal activity associated with protective immunity. To expand the antigen repertoire and to design a more broadly protective vaccine, NadA-PhaC beads were additionally conjugated to the capsular polysaccharide from serogroup C. Co-delivery of surface displayed NadA and the capsular polysaccharide induced a strong and specific Th1/Th17 mediated immune response associated with functional bactericidal antibodies. Our findings provide the foundation for the design of multivalent antigen-coated polyester beads as suitable carriers for protein and polysaccharide antigens in order to induce protective immunity.
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http://dx.doi.org/10.1038/s41598-018-20205-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789850PMC
January 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

Self-assembled particulate PsaA as vaccine against infection.

Heliyon 2017 Apr 11;3(4):e00291. Epub 2017 Apr 11.

Institute of Fundamental Sciences and MacDiarmid Institute of Advanced Materials and Nanotechnology, Massey University, Palmerston North, New Zealand.

is a human pathogen responsible for the majority of childhood pneumonia and media otitis cases worldwide. The diversity of its capsular polysaccharides (CPS) results in more than 91 serotypes of which at least 23 are virulent. Various CPS conjugated to immunogenic carrier proteins are currently licensed and provide protection against the infection caused by the respective serotypes but not against new and emerging virulent serotypes. In this study, we considered the conserved protein antigen PsaA, the pneumococcal surface adhesin A, in order to overcome the limitations of CPS antigens. The PsaA was translationally fused to a polyhydroxybutyrate (PHB) synthase which mediated production of PsaA displayed on PHB inclusions in recombinant . This suggested that the PsaA fusion to the PHB synthase did not interfere with PHB synthase activity and its ability to mediate formation of nano-sized inclusions composed of a PHB core surrounded by the PHB synthase fused to PsaA. Isolated PHB beads showed a negative surface charge. Transmission electron microscopy analysis suggested that the PsaA fusion to the PHB synthase reduced the size of PHB beads from about 500 nm to 100 nm. The integrity and antigenicity of the fusion protein attached to isolated PHB beads was confirmed by SDS-PAGE, tryptic peptide fingerprinting analysis using MALDI-TOF-MS/MS and immunoblotting using a monoclonal anti-PsaA antibody. Mice immunized with PsaA displaying PHB beads produced high and specific IgG levels dominated by IgG1 isotype. While IgG1 titer were similar between soluble and insoluble PsaA, the IgG2 titers were strongly increased upon vaccination with insoluble PsaA i.e. PsaA displayed on PHB beads. Particulate PsaA-PHB beads elicited IgG antibodies recognizing PsaA in whole cell lysates of seven different serotypes of This study suggested that PHB beads are suitable carriers for PsaA in order to induce a significant and specific Th-2-type immune response.
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http://dx.doi.org/10.1016/j.heliyon.2017.e00291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390691PMC
April 2017

Influence of the Co-Administration of Heptavalent Conjugate Vaccine PCV7-TT on the Immunological Response Elicited by VA-MENGOC-BC® and Heberpenta®-L in Rabbits.

Immunol Invest 2017 May 5;46(4):395-408. Epub 2017 Apr 5.

a Finlay Vaccine Institute , Havana , Cuba.

Finlay Vaccine Institute is developing a new heptavalent conjugate vaccine against Streptococcus pneumoniae. As infants are the target population, PCV7-TT will be necessarily co-administered with other vaccines, and then, the interactions represent a concern. The aim of this work is to evaluate the possible immunological interferences in rabbits as animal experimental model. Rabbits were immunized with Heberpenta®-L, VA-MENGOC-BC®, and PCV7-TT. Blood samples were taken fourteen days after final immunization for obtaining sera. Antibody responses to all antigens were evaluated by indirect ELISA. Functional responses against diphtheria and tetanus toxoid were done by in vivo seroneutralization assay. No interference was observed by PCV7-TT over the humoral response against diphtheria toxoid and meningococcal antigens (p > 0.05). A nonstatistically significant reduction (p > 0.05) was observed in the case of the humoral response against Haemophilus influenzae type b oligosaccharide. Concomitant administration of Heberpenta®-L and PCV7-TT increased twice the antibody titers as well as the protective activity against tetanus toxoid, but no statistical differences were found. The co-administration did not induce a reduction in the percent of responders against pneumococcal polysaccharides contained in PCV7-TT vaccine. Concomitant administration of PCV7-TT did not induce interferences over the evaluated antigens of Heberpenta®-L and VA-MENGOC-BC®. Also, no interference was observed on the immune response elicited by PCV7-TT. These preclinical results suggest that PCV7-TT will not result in a serious problem over the immune response elicited by the licensed vaccines Heberpenta®-L and VA-MENGOC-BC®. However, the clinical interference could be strictly studied during clinical trials in infants.
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http://dx.doi.org/10.1080/08820139.2017.1288238DOI Listing
May 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

Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial.

Vaccine 2014 Sep 26;32(41):5266-70. Epub 2014 Jul 26.

Center for Biomolecular Chemistry, 200 and 21 Street, Playa, Havana 11600, Cuba.

A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173.
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http://dx.doi.org/10.1016/j.vaccine.2014.06.094DOI Listing
September 2014

Mangifera indica L. extract (Vimang) and mangiferin reduce the airway inflammation and Th2 cytokines in murine model of allergic asthma.

J Pharm Pharmacol 2011 Oct;63(10):1336-45

Laboratory of Pharmacology, Department of Biomedical Research, Center for Pharmaceutical Chemistry, Atabey, Playa, Havana City, Cuba.

Objectives: The aim was to study the effects of Mangifera indica extract and its major component mangiferin on lung inflammation response and Th2 cytokine production using a murine experimental model of allergic asthma.

Methods: BALB/c mice were intraperitoneally sensitized with 10 µg of ovoalbumin (OVA) adsorbed on aluminium hydroxide on days 0, 7 and 14. Seven days after the last injection, the mice were challenged with 2% aerosolized OVA inhalation for 30 min beginning on day 21 and continuing until day 24. To evaluate the protective effect, mice were orally treated with M. indica extract (50, 100 or 250 mg/kg) or mangiferin (50 mg/kg) from days 0 to 24. Anti-OVA immunoglobulin E, interleukin (IL)-4 and IL-5 were determined by ELISA and lungs were analysed by histology.

Key Findings: M. indica extract and mangiferin produced a marked reduction of airway inflammation around vessels and bronchi, inhibition of IL-4 and IL-5 cytokines in bronchoalveolar lavage fluid and lymphocyte culture supernatant, IgE levels and lymphocyte proliferation.

Conclusion: This is the first pre-clinical report of the anti-inflammatory properties of M. indica extract and mangiferin in experimental asthma and it could be an important part of pre-clinical requirement necessary for its use to complement the treatment of this complex disease.
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http://dx.doi.org/10.1111/j.2042-7158.2011.01328.xDOI Listing
October 2011

Gallic acid indanone and mangiferin xanthone are strong determinants of immunosuppressive anti-tumour effects of Mangifera indica L. bark in MDA-MB231 breast cancer cells.

Cancer Lett 2011 Jun 21;305(1):21-31. Epub 2011 Mar 21.

Laboratory of Pharmacology, Center for Pharmaceutical Chemistry, Atabey, Havana City, Cuba.

Vimang is a standardized extract derived from Mango bark (Mangifera Indica L.), commonly used as anti-inflammatory phytomedicine, which has recently been used to complement cancer therapies in cancer patients. We have further investigated potential anti-tumour effects of glucosylxanthone mangiferin and indanone gallic acid, which are both present in Vimang extract. We observed significant anti-tumour effects of both Vimang constituents in the highly aggressive and metastatic breast cancer cell type MDA-MB231. At the molecular level, mangiferin and gallic acid both inhibit classical NFκB activation by IKKα/β kinases, which results in impaired IκB degradation, NFκB translocation and NFκB/DNA binding. In contrast to the xanthone mangiferin, gallic acid further inhibits additional NFκB pathways involved in cancer cell survival and therapy resistance, such as MEK1, JNK1/2, MSK1, and p90RSK. This results in combinatorial inhibition of NFκB activity by gallic acid, which results in potent inhibition of NFκB target genes involved in inflammation, metastasis, anti-apoptosis and angiogenesis, such as IL-6, IL-8, COX2, CXCR4, XIAP, bcl2, VEGF. The cumulative NFκB inhibition by gallic acid, but not mangiferin, is also reflected at the level of cell survival, which reveals significant tumour cytotoxic effects in MDA-MB231 cells. Altogether, we identify gallic acid, besides mangiferin, as an essential anti-cancer component in Vimang extract, which demonstrates multifocal inhibition of NFκB activity in the cancer-inflammation network.
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http://dx.doi.org/10.1016/j.canlet.2011.02.011DOI Listing
June 2011

The paradox of natural products as pharmaceuticals. Experimental evidences of a mango stem bark extract.

Pharmacol Res 2007 May 16;55(5):351-8. Epub 2007 Jan 16.

Center of Pharmaceutical Chemistry, 21 Ave. & 200 St., Atabey, Apdo. 16042, CP 11600 Havana, Cuba.

Recent findings regarding basic, pre-clinical and clinical studies on a mango stem bark extract (MSBE) developed in Cuba (Vimang) on an industrial scale are summarized. Ethnomedical studies, extract reproducibility, biological effects and clinical evaluations in terms of patient quality of life are described as experimental evidences to support the statement that natural products, even being a mixture of compounds, could be as effective as "monoceuticals" for medical uses. Discussion about the use of "monoceuticals" versus "natureceuticals" in health care and medicine is based on effectiveness and availability, taking Vimang as an example of a natural product with supported scientific evidence to be used as antioxidant, analgesic, anti-inflammatory and immunomodulator.
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http://dx.doi.org/10.1016/j.phrs.2007.01.004DOI Listing
May 2007

Anti-allergic properties of Mangifera indica L. extract (Vimang) and contribution of its glucosylxanthone mangiferin.

J Pharm Pharmacol 2006 Mar;58(3):385-92

Laboratory of Pharmacology, Department of Biomedical Research, Center of Pharmaceutical Chemistry, P. O. Box 16042, Havana, Cuba.

Vimang is the brand name of formulations containing an extract of Mangifera indica L., ethnopharmacologically used in Cuba for the treatment of some immunopathological disorders, including bronchial asthma, atopic dermatitis and other allergic diseases. However, the effects of Vimang on allergic response have not been reported until now. In this study, the effects of Vimang and mangiferin, a C-glucosylxanthone isolated from the extract, on different parameters of allergic response are reported. Vimang and mangiferin showed a significant dose-dependent inhibition of IgE production in mice and anaphylaxis reaction in rats, histamine-induced vascular permeability and the histamine release induced by compound 48/80 from rat mast cells, and of lymphocyte proliferative response as evidence of the reduction of the amount of B and T lymphocytes able to contribute to allergic response. In these experiments, ketotifen, promethazine and disodium cromoglicate were used as reference drugs. Furthermore, we demonstrated that Vimang had an effect on an in-vivo model of inflammatory allergy mediated by mast cells. These results constitute the first report of the anti-allergic properties of Vimang on allergic models, as well as suggesting that this natural extract could be successfully used in the treatment of allergic disorders. Mangiferin, the major compound of Vimang, contributes to the anti-allergic effects of the extract.
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http://dx.doi.org/10.1211/jpp.58.3.0014DOI Listing
March 2006
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