ngonzalez@finlay.edu.cu. Figure 1. Subject disposition. PHASE I CLINICAL TRIAL OF A CUBAN 7-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN HEALTHY INFANTS. Authors: González N1; Paredes B1; Dotres CP2; Puga R2; Ricardo Y2; García Y2; del Valle RA2; Mora S3, Viera T3, Tasse S3, Echemendía V1; García D1; Rodríguez Y1; Iglesias A1; Santana D1; ValdésY1; Burbidge P4; Johnson M4; Goldblatt D4; Vérez V1. Finlay Institute. Ave 27, No. 19805, La Lisa. La Habana, Cuba. 2. Children University Hospital “Juan Manuel Márquez”. Havana. Cuba. 3. Primary Health System from Marianao. Havana. Cuba. 4. Institute of Child Health. London. United Kingdom.. ngonzalez@finlay.edu.cu. INTRODUCTION A new pneumococcal conjugate vaccine (PCV7-TT) have been designed in Cuba containing seven serotypes of Streptococcus pneumoniae representing the most frequently associated with infections in Latina-America [1, 2]. PCV7-TT contains 2µg of serotypes 1, 5, 14, 18C, 19F and 23F and 4µg of 6B, each conjugated to tetanus toxoid (TT) and aluminum phosphate is used as adjuvant. The safety of PCV7-TT was previously demonstrated in healthy young adults during a phase I clinical trial in 2012. Also, as a first stage of the present study a randomized Phase I clinical trial in children 4-5 years old was made [3]. The current Phase I clinical trial had the aim of assess the safety and preliminary immunogenicity of PCV7-TT in 30 infants 7-8 months of age. This is the main population for which the vaccine was designed. Material And Methods A phase I controlled double blind clinical trial was designed to assess the safety and preliminary immunogenicity of the candidate vaccine PCV7-TT in 30 infants 7-8 months of age. The protocol was reviewed by the Ethics Committee of Children University Hospital “Juan Manuel Márquez”. It was conducted in accordance with the code of Ethic of the World Medical Association for experiments in human beings [4]. Infants were randomized to receive an outline of two primary doses with an interval of four weeks and a booster 3 months after the second dose of VCN7-T (n = 20) or Synflorix (n = 10). PCV7-TT (Batch Neu-13.02, Manufacturer: Center for Bimolecular Chemistry, Cuba) contains 2mg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 mg of serotype 6B, each conjugated to TT and Synflorix vaccine (Batch ASPNA305AA, Manufacturer: GSK) was used as a control. Blood samples were taken 30 days after the second dose and 30 days after booster dose. Serotype specific OPA and ELISA were performed at the WHO Reference Laboratory, UCL Institute of Child Health in London [5,6]. Local injection-site adverse events (local pain, tenderness, redness, induration, swelling, local temperature increase, functional impotence, abscess or necrosis) and systemic symptoms (fever, anaphylactic shock, drowsiness, nausea, vomits and headache) were recorded during the first 7 days after vaccination. Any other events occurring with the infants was recorded by the parents during 30 days. Statistics: Randomization 1:2 was used to assign 20 subject to the group PCV7-TT and 10 subjects to the group Synflorix. A non-parametric test (Fisher’s Exact Test for Count Data) was used to compare incidence for each adverse event and percentages of occurrence for adverse events were calculated in both groups. Immunogenicity data were reported as serotype specific antipolysaccharide geometric mean IgG antibody concentrations with 2-sided 95% confidence intervals. Functional antibody activity (OPA) was reported as geometric mean titer with 2-sided 95% confidence intervals. Screened 36 Incluided 30 VCN7-T 20 Withdrawn post 1rst dose 1 Parent request Synflorix 10 Not incluided 6 Figure 1. Subject disposition. Results A total of 36 subjects were evaluated for inclusion and 30 were included (Figure 1). Demographic characteristic of the two groups were comparable for gender, ethnicity and age. The adverse events reported were comparable between both vaccines and PCV7-TT showed a good safety profile. No serious related adverse events were reported using PCV7-TT. After the schedule, in PCV7-TT arm, induration was the most frequent local adverse event and fever was the most common systemic event in all of doses (Table 1). ADVERSE EVENTS 1st dose 2nd dose Booster dose VCN7-T Synflorix N=20 N=10 N=19 n % Expectedd Local Events Local Pain 3 15 1 10 5 Redness 8 40 4 21 16 Induration 50 26 2 20 Expected Systemics Events Fever ≥38.00C Vomits Table 1. Adverse events in subjects vaccinated with PCV7-TT or Synflorix . IgG Geometric Mean Concentrations (GMCs) and OPA Geometric Mean Titers (GMTs) for the seven serotypes shared by both vaccines were comparable between groups. After the booster dose, 100% of infants in PCV7-TT arm had OPA ≥ 8 for all serotypes (Figure 2). Serotype-specific pneumococcal IgG concentrations ≥0.35 µg/mL were achieved in 100% of infants in PCV7-TT group for 6 serotypes: 1, 14, 18C, 19F, 23F and 6B. Seroprotection was achieved in 94.7% of infants in PCV7-TT group for serotype 5 (Figure 3). Porcentaje de sujetos con ELISA ≥ 0.20 µg/mL Figure 2. % of subjects with OPA titer ≥1:8 post-second dose and post-booster dose. Figure 3. % of subjects with con ELISA ≥ 0.20 µg/mL post-second dose and post-booster dose. REFERENCES CONCLUSIONS [1] Johnson HL et al. PLoS Med 2010;7:1-13 [2] Castañeda E et al. Pediatr Infect Dis J 2009;28:e265-70 [3] Dotres CP et al. Vaccine. 2014;32(41):5266-70 [4] WMA. Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. [2008 Oct; cited 2011 Jan 15]; Available from: http://www.wma.net/en/30publications/10policies/b3/17c.pdf. [4] Training manual for Enzyme linked immunosorbent assay for the quantitation of Streptococcus pneumoniae serotype specific IgG (Pn PS ELISA). (007sp Version). Available from: www.vaccine.uab.edu [5] Protocol for multiplexed opsonophagocytic killing assay (UAB-MOPA) for antibodies against Streptococcus pneumonia. Available from: www.vaccine.uab.edu [6] Scott DA et al. Vaccine 2007;25:6164-6. [7] Bryant KA et al. Pediatrics 2010;125:866 PCV7-TT was as safe as control vaccine Synflorix in infants 7-8 month of aged. The totality of infants seroprotected by OPA after the schedule for all serotype in PCV7-TT. Seroprotection by ELISA were achieved in all of subjects in PCV7-TT group for 6 serotypes.