Real-world effectiveness of the heterologous SOBERANA-02 and SOBERANA-Plus vaccine scheme in 2-11 years-old children during the SARS-CoV-2 Omicron wave in Cuba: a longitudinal case-population study.

Background: Increased pediatric COVID-19 occurrence due to the SARS-CoV-2 Omicron variant has raised concerns about the effectiveness of existing vaccines. The protection provided by the SOBERANA-02-Plus vaccination scheme against this variant has not yet been studied. We aimed to evaluate the scheme's effectiveness against symptomatic Omicron infection and severe disease in children. Methods: In September 2021, Cuba implemented a mass pediatric immunization with the heterologous SOBERANA-02-Plus scheme: 2 doses of conjugated SOBERANA-02 followed by a heterologous SOBERANA-Plus dose. By December, before the Omicron outbreak, 95.4% of 2-18 years-old had been fully immunized. During the entire Omicron wave, we conducted a nationwide longitudinal post-vaccination case-population study to evaluate the real-world effectiveness of the SOBERANA-02-Plus scheme against symptomatic infection and severe disease in children without previous SARS-CoV-2 infection. The identification of COVID-19 cases relied on surveillance through first line services, which refer clinical suspects to pediatric hospitals where they are diagnosed based on a positive RT-PCR test. We defined the Incidence Rate ratio (IRR) as IRvaccinated age group/IRunvaccinated 1-year-old and calculated vaccine effectiveness as VE = (1-IRR)∗100%. 24 months of age being the 'eligible for vaccination' cut-off, we used a regression discontinuity approach to estimate effectiveness by contrasting incidence in all unvaccinated 1-year-old versus vaccinated 2-years-old. Estimates in the vaccinated 3-11 years-old are reported from a descriptive perspective. Findings: We included 1,098,817 fully vaccinated 2-11 years-old and 98,342 not vaccinated 1-year-old children. During the 24-week Omicron wave, there were 7003/26,241,176 person-weeks symptomatic COVID-19 infections in the vaccinated group (38.2 per 105 person-weeks in 2-years-old and 25.5 per 105 person-weeks in 3-11 years-old) against 3577/2,312,273 (154.7 per 105 person-weeks) in the unvaccinated group. The observed overall vaccine effectiveness against symptomatic infection was 75.3% (95% CI, 73.5-77.0%) in 2-years-old children, and 83.5% (95% CI, 82.8-84.2%) in 3-11 years-old. It was somewhat lower during Omicron BA.1 then during Omicron BA.2 variant circulation, which took place 1-3 and 4-6 months after the end of the vaccination campaign. The effectiveness against severe symptomatic disease was 100.0% (95% CI not estimated) and 94.6% (95% CI, 82.0-98.6%) in the respective age groups. No child death from COVID-19 was observed. Interpretation: Immunization of 2-11 years-old with the SOBERANA-02-Plus scheme provided strong protection against symptomatic and severe disease caused by the Omicron variant, which was sustained during the six months post-vaccination follow-up. Our results contrast with the observations in previous real-world vaccine effectiveness studies in children, which might be explained by the type of immunity a conjugated protein-based vaccine induces and the vaccination strategy used. Funding: National Fund for Science and Technology (FONCI-CITMA-Cuba).

Open-label phase I/II clinical trial of SARS-CoV-2 receptor binding domain-tetanus toxoid conjugate vaccine (FINLAY-FR-2) in combination with receptor binding domain-protein vaccine (FINLAY-FR-1A) in children.

OBJECTIVES: To evaluate a heterologous vaccination scheme in children 3-18 years old (y/o) combining two SARS-CoV-2r- receptor binding domain (RBD)protein vaccines. METHODS: A phase I/II open-label, adaptive, and multicenter trial evaluated the safety and immunogenicity of two doses of FINLAY-FR-2 (subsequently called SOBERANA 02) and the third heterologous dose of FINLAY-FR-1A (subsequently called SOBERANA Plus) in 350 children 3-18 y/o in Havana Cuba. Primary outcomes were safety (phase I) and safety/immunogenicity (phase II) measured by anti-RBD immunoglobulin (Ig)G enzyme-linked immunoassay (ELISA), molecular and live-virus neutralization titers, and specific T-cells response. A comparison with adult immunogenicity and predictions of efficacy were made based on immunological results. RESULTS: Local pain was the unique adverse event with frequency >10%, and none was serious neither severe. Two doses of FINLAY-FR-2 elicited a humoral immune response similar to natural infection; the third dose with FINLAY-FR-1A increased the response in all children, similar to that achieved in vaccinated young adults. The geometric mean (GMT) neutralizing titer was 173.8 (95% confidence interval [CI] 131.7; 229.5) vs Alpha, 142 (95% CI 101.3; 198.9) vs Delta, 24.8 (95% CI 16.8; 36.6) vs Beta and 99.2 (95% CI 67.8; 145.4) vs Omicron. CONCLUSION: The heterologous scheme was safe and immunogenic in children 3-18 y/o. TRIAL REGISTRY: https://rpcec.sld.cu/trials/RPCEC00000374.

Safety and immunogenicity of anti-SARS-CoV-2 heterologous scheme with SOBERANA 02 and SOBERANA Plus vaccines: Phase IIb clinical trial in adults.

BACKGROUND: SOBERANA 02 has been evaluated in phase I and IIa studies comparing homologous versus heterologous schedule (this one, including SOBERANA Plus). Here, we report results of immunogenicity, safety, and reactogenicity of SOBERANA 02 in a two- or three-dose heterologous scheme in adults. METHOD: Phase IIb was a parallel, multicenter, adaptive, double-blind, randomized, and placebo-controlled trial. Subjects (n = 810) aged 19-80 years were randomized to receive two doses of SARS-CoV-2 RBD conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredients of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with ≥4-fold the anti-RBD immunoglobulin G (IgG) concentration. Secondary outcomes were safety, reactogenicity, and neutralizing antibodies. FINDINGS: Seroconversion rate in vaccinees was 76.3% after two doses and 96.8% after the third dose of SOBERANA Plus (7.3% in the placebo group). Neutralizing IgG antibodies were detected against D614G and variants of concern (VOCs) Alpha, Beta, Delta, and Omicron. Specific, functional antibodies were detected 7-8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%). Local pain was the most frequent AE. CONCLUSIONS: Two doses of SOBERANA 02 were safe and immunogenic in adults. The heterologous combination with SOBERANA Plus increased neutralizing antibodies, detectable 7-8 months after the third dose. TRIAL REGISTRY: https://rpcec.sld.cu/trials/RPCEC00000347 FUNDING: This work was supported by Finlay Vaccine Institute, BioCubaFarma, and the Fondo Nacional de Ciencia y Técnica (FONCI-CITMA-Cuba, contract 2020-20).

Safety and immunogenicity of anti-SARS CoV-2 vaccine SOBERANA 02 in homologous or heterologous scheme: Open label phase I and phase IIa clinical trials.

BACKGROUND: SOBERANA 02 is a COVID-19 vaccine based on SARS-CoV-2 recombinant RBD conjugated to tetanus toxoid (TT). SOBERANA Plus antigen is dimeric-RBD. Here we report safety and immunogenicity from phase I and IIa clinical trials using two-doses of SOBERANA 02 and three-doses (homologous) or heterologous (with SOBERANA Plus) protocols. METHOD: We performed an open-label, sequential and adaptive phase I to evaluate safety and explore the immunogenicity of SOBERANA 02 in two formulations (15 or 25 µg RBD-conjugated to 20 µg of TT) in 40 subjects, 19-59-years-old. Phase IIa was open-label including 100 volunteers 19-80-years, receiving two doses of SOBERANA 02-25 µg. In both trials, half of volunteers were selected to receive a third dose of the corresponding SOBERANA 02 and half received a heterologous dose of SOBERANA Plus. Primary outcome was safety. The secondary outcome was immunogenicity evaluated by anti-RBD IgG ELISA, molecular neutralization of RBD:hACE2 interaction, live-virus-neutralization and specific T-cells response. RESULTS: The most frequent adverse event (AE) was local pain, other AEs had frequencies ≤ 5%. No serious related-AEs were reported. Phase IIa confirmed the safety in 60 to 80-years-old subjects. In phase-I SOBERANA 02-25 µg elicited higher immune response than SOBERANA 02-15 µg and progressed to phase IIa. Phase IIa results confirmed the immunogenicity of SOBERANA 02-25 µg even in 60-80-years. Two doses of SOBERANA02-25 µg elicited an immune response similar to that of the Cuban Convalescent Serum Panel and it was higher after the homologous and heterologous third doses. The heterologous scheme showed a higher immunological response. Anti-RBD IgG neutralized the delta variant in molecular assay, with a 2.5-fold reduction compared to D614G neutralization. CONCLUSIONS: SOBERANA 02 was safe and immunogenic in persons aged 19-80 years, eliciting neutralizing antibodies and specific T-cell response. Highest immune responses were obtained in the heterologous three doses protocol. TRIAL REGISTRY: https://rpcec.sld.cu/trials/RPCEC00000340, https://rpcec.sld.cu/trials/RPCEC00000347.

A COVID-19 vaccine candidate composed of the SARS-CoV-2 RBD dimer and Neisseria meningitidis outer membrane vesicles.

SARS-CoV-2 infection is mediated by the interaction of the spike glycoprotein trimer via its receptor-binding domain (RBD) with the host's cellular receptor. Vaccines seek to block this interaction by eliciting neutralizing antibodies, most of which are directed toward the RBD. Many protein subunit vaccines require powerful adjuvants to generate a potent antibody response. Here, we report on the use of a SARS-CoV-2 dimeric recombinant RBD combined with Neisseria meningitidis outer membrane vesicles (OMVs), adsorbed on alum, as a promising COVID-19 vaccine candidate. This formulation induces a potent and neutralizing immune response in laboratory animals, which is higher than that of the dimeric RBD alone adsorbed on alum. Sera of people vaccinated with this vaccine candidate, named Soberana01, show a high inhibition level of the RBD-ACE2 interaction using RBD mutants corresponding to SARS-CoV-2 variants of concern and wild-type expressed using the phage display technology. To our knowledge, this is the first time that the immunostimulation effect of N. meningitidis OMVs is evaluated in vaccine candidates against SARS-CoV-2.

Repeat-dose and local tolerance toxicity of SARS-CoV-2 FINLAY-FR-02 vaccine candidate in Sprague Dawley rats.

This study evaluates safety of FINLAY-FR-02, a vaccine candidate against SARS-CoV-2 based on the recombinant receptor binding domain conjugated to tetanus toxoid, in a preclinical, repeat-dose toxicity and local tolerance study. Sprague Dawley rats were randomly allocated to three experimental groups: control (receiving physiological saline solution); placebo (receiving all vaccine components except antigens) and vaccine group (receiving three doses of the vaccine candidate, 37.5 µg of RBD) administered intramuscularly in hind limbs at 24 h intervals during three days. We evaluated physiological condition, pain, food and water consumption, body temperature, dermal irritability, injection site temperature and inflammation, immunological response, blood chemistry, relative organ weight, histopathology and immunotoxicology. The product was well tolerated; no clinically relevant changes, pain, local effects or adverse systemic toxicological changes or deaths were observed. These preliminary results permitted the Cuban regulatory authorities to authorize clinical trials in humans.

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

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 Streptococcus pneumoniae (Sp) 19A and 19F. The CPS repeating units of Sp 19F and 19A are very similar and share a common structure, the disaccharide ManNAc-ß-(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.

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

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.

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

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.

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

Conjugate vaccines against encapsulated pathogens like Streptococcus pneumoniae 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 S. pneumoniae, 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 S. pneumoniae. The glycoconjugates were able to elicit functional specific antibodies against pneumococcal strains comparable to those shown by mixtures of the two monovalent glycoconjugates.

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

Streptococcus pneumoniae can cause life-threatening infections mostly in infants, children, and elderly people. Capsular polysaccharide conjugate vaccines provide serotype-dependent protection against S. pneumoniae 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 Escherichia coli. 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 S. pneumoniae. 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.

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

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.

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

La nueva vacuna cubana antineumocócica, de las evidencias científicas disponibles, a la estrategia de evaluación clínica y de impacto / New Cuban pneumococcal vaccine, from available scientific evidence to the strategy of clinical and impact evaluation

Este trabajo resume el marco de evidencias que sustenta el actual uso de las vacunas antineumocócicas conjugadas en términos de seguridad, inmunogenicidad, eficacia y efectividad. Presenta una nueva alternativa para prevenir la enfermedad neumocócica en la población infantil basada en el nuevo candidato vacunal cubano contra neumococo. Expone los principios básicos que definen la estrategia para su introducción en Cuba, y los avances derivados de la aplicación de un modelo integrado para la evaluación clínica e impacto en salud en fase de implementación, el cual busca proveer las evidencias científicas que soporten la decisión del sistema nacional de salud para su introducción en el esquema nacional de inmunizaciones y su posterior comercialización en la era de las vacunas conjugadas antineumocócicas. Se presentan los resultados preliminares de estudios concluidos, y se elaboran conclusiones sobre los aportes científicos y prácticos de la estrategia de implementación y el modelo de evaluación para la nueva vacuna(AU)

This paper summarized the group of evidence that supports the present use of the pneumococcal conjugate vaccines in terms of safety, immunogenicity, efficacy and effectiveness. It offers a new alternative to prevent the pneumococcal disease in the infant population on the basis of a new Cuban vaccinal candidate against pneumococci. It set out the basic principles that define the strategy for the introduction of this vaccine in Cuba and the advances resulting from the use of an integrated model for the clinical evaluation and the impact on health, in its implementation phase, which seeks to provide the scientific evidence backing up the decision of the national health care system to introduce this vaccine in the national immunization schedule and its further commercialization in the era of pneumococcal conjugate vaccines. Preliminary results of finished studies were presented and the conclusions on the scientific and practical contributions of the strategy of implementation and the evaluation model for the new vaccine were worked out(AU)

Activación del polisacárido capsular de Streptococcus pneumoniae serotipo 23F para la obtención de vacunas conjugadas / Activation of the capsular polysaccharide serotype 23F of Streptococcus pneumoniae to obtain conjugate vaccine

En la actualidad, las vacunas conjugadas constituyen un gran hito en el desarrollo de fármacos que protegen contra las enfermedades infecciosas. Estas vacunas no solo disminuyen drásticamente la mortalidad y morbilidad de diferentes enfermedades causadas por bacterias en la población infantil; sino que también repercuten sobre la población no vacunada. Las vacunas conjugadas se basan en establecer una unión covalente entre un polisacárido y una proteína portadora para lo cual existen diferentes procedimientos químicos. Todos los procedimientos de conjugación requieren la presencia de grupos reactivos complementarios que muchas veces son generados en ambas macromoléculas. Este trabajo se enfoca en el estudio de la reacción de fragmentación y de la oxidación peryódica sobre el polisacárido capsular serotipo 23F de Streptococcus pneumoniae para su uso como antígeno vacunal. Se estableció la fragmentación del polisacárido mediante hidrólisis con ácido acético y trifluoroácetico. En el caso de la reacción de oxidación se encontró que la cantidad de moles de peryodato de sodio y la temperatura influyen de manera directamente proporcional sobre la generación de grupos carbonilos. Adicionalmente se demostró que el sustituyente glicerol-fosfatos presente en la estructura del serotipo 23F es relevante para conservar la antigenicidad. El procedimiento descrito permite obtener conjugados inmunogénicos a partir del polisacárido capsular de Streptococcus pneumoniae serotipo 23F en el modelo de conejo(AU)

Nowadays conjugate vaccines are a major milestone in the development of drugs against infectious diseases. These vaccines drastically reduce mortality and morbidity from different diseases caused by bacteria in children; but also impact on non-vaccinated population. Conjugate vaccines are based on a covalent bond between a polysaccharide and a carrier protein for which there are different chemical procedures. All conjugate procedures require the presence of additional reactive groups that often are generated in both macromolecules. This work focus on the study of the fragmentation reaction and peryodic oxidation on the capsular polysaccharide serotype 23F Streptococcus pneumoniae for use as a vaccine antigen. It was possible to establish the fragmentation reaction of the polysaccharide by hydrolysis with acetic and trifluoroacetic acid. Directly proportional ratio was found between numbers of moles of sodium periodate and temperature on the oxidation reactions. In addition the glycerol-phosphate substituent was found as important motif to preserve the antigenicity. The procedure allows immunogenic conjugate from capsular polysaccharide serotype 23F of Streptococcus pneumoniae in rabbit models(AU)

Activación del polisacárido capsular de Streptococcus pneumoniae serotipo 23F para la obtención de vacunas conjugadas / Activation of the capsular polysaccharide serotype 23F of Streptococcus pneumoniae to obtain conjugate vaccine

En la actualidad, las vacunas conjugadas constituyen un gran hito en el desarrollo de fármacos que protegen contra las enfermedades infecciosas. Estas vacunas no solo disminuyen drásticamente la mortalidad y morbilidad de diferentes enfermedades causadas por bacterias en la población infantil; sino que también repercuten sobre la población no vacunada. Las vacunas conjugadas se basan en establecer una unión covalente entre un polisacárido y una proteína portadora para lo cual existen diferentes procedimientos químicos. Todos los procedimientos de conjugación requieren la presencia de grupos reactivos complementarios que muchas veces son generados en ambas macromoléculas. Este trabajo se enfoca en el estudio de la reacción de fragmentación y de la oxidación peryódica sobre el polisacárido capsular serotipo 23F de Streptococcus pneumoniae para su uso como antígeno vacunal. Se estableció la fragmentación del polisacárido mediante hidrólisis con ácido acético y trifluoroácetico. En el caso de la reacción de oxidación se encontró que la cantidad de moles de peryodato de sodio y la temperatura influyen de manera directamente proporcional sobre la generación de grupos carbonilos. Adicionalmente se demostró que el sustituyente glicerol-fosfatos presente en la estructura del serotipo 23F es relevante para conservar la antigenicidad. El procedimiento descrito permite obtener conjugados inmunogénicos a partir del polisacárido capsular de Streptococcus pneumoniae serotipo 23F en el modelo de conejos(AU)

Nowadays conjugate vaccines are a major milestone in the development of drugs against infectious diseases. These vaccines drastically reduce mortality and morbidity from different diseases caused by bacteria in children; but also impact on non-vaccinated population. Conjugate vaccines are based on a covalent bond between a polysaccharide and a carrier protein for which there are different chemical procedures. All conjugate procedures require the presence of additional reactive groups that often are generated in both macromolecules. This work focus on the study of the fragmentation reaction and peryodic oxidation on the capsular polysaccharide serotype 23F Streptococcus pneumoniae for use as a vaccine antigen. It was possible to establish the fragmentation reaction of the polysaccharide by hydrolysis with acetic and trifluoroacetic acid. Directly proportional ratio was found between numbers of moles of sodium periodate and temperature on the oxidation reactions. In addition the glycerol-phosphate substituent was found as important motif to preserve the antigenicity. The procedure allows immunogenic conjugate from capsular polysaccharide serotype 23F of Streptococcus pneumoniae in rabbit models(AU)