13. Representación esquemática de la Partícula del Virus Influenza Poner gráfico escaneado CL: capa lipídica CRNP: Complejo ribonucleoproteico-polimerasas PA, PB1 y PB2 HA: Hemaglutinina NA: Neuraminidasa M1: Proteína M2: Proteína M2 Las proyecciones HA y NA están dispuestas en la superficie del virión y enclavadas en la CL, ubicada sobre la proteína M1. En el interior de la partícula se encuentran 8 segmentos del RNA viral junto a la nucleoproteína y a las polimerasas, integrantes del CRNP.
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20. Distribución de casos internados por Infección Respiratoria Aguda Baja Viral Año 2009*. N°casos Semana Epidemiológica n=320 *Hasta semana epidemiológica 34 (29 de Agosto de 2009)
21. Distribución de casos internados por Infección Respiratoria Aguda Baja por Virus Influenza. Años 2007-2008-2009*. N°casos Semana Epidemiológica n=131 *Hasta semana epidemiológica 34 (29 de Agosto de 2009)
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23. Casos % >= 5 años < 5 años n=120 Edad 5 años 18.8 81,2 1.2 98.8 RR 15.75 (1.97-125)
25. Casos % ARM No ARM n=120 Asistencia Ventilatoria Mecánica (ARM) 44.4 55.6 2.8 97.2 RR 27.47 (3.74-230)
26. Casos % Con C sin C n=120 Complicaciones (C) 16.6 83.4 1.3 98.7 RR 15.04 (1.71-354)
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34. AFLUNOV (H5N1 + MF59 ) Niveles de anticuerpos luego de 2 dosis. Esquema 0-21 días Microneutralizacion Cepa H5N1 Vietnam * ClinicalTrials.gov Identifier: NCT00382187 Data from V87P, Galli G et al . PNAS, 2009; in press. 15 μg / nil (n=13) 7.5 μ g / MF59 AFLUNOV (n=14) Esquema * Diferencia estadisticamente significativa ( P <0.01) * Días post-primera vacunación MN títulos de anticuerpos (GMT) 0 20 40 60 80 100 120 0 21 42 Estudio Fase II aleatorizado, controlado, ciego al observador, solo en un centro, en adultos (N=27)
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39. A(H1N1) – clinical data slide deck Data inclusion status: FOCETRIA platform L, local S, systemic Sv, severe HI, hemaglutinnin inhibition HI40, HI titer≥1:40 SC, seroconversion mth, months yrs, years N/A, not available currently MN, microneutralization MN40, MN titer≥1:40 USR, unsolicited reactions For APPROVAL – Sally, Nicola/Joe, Luiz and Lamberto must review Study Phase Age group Safety Immunogenicity GMCC approved Data Up to day Data Up to day FOCETRIA platform V111_02 II ≥ 18 yrs L,S, USR 42 HI40, SC, GMR, GMT, MN40, MN 42 21 Approved V111_03 II 6 mth – 17yrs USR/SR 28 HI40, SC, GMR, GMT 6 – 35 mth: N/A 3 – 8 yrs: 21 9 – 17 yrs: 42 Approved V111_04 II ≥ 18 yrs L, S, USR 21 HI40, SC, GMT, GMR 21 Approved Seasonal immunogenicity 21 Approved L, S, USR 42 HI40, SC, GMT, GMR 42 Approved
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41. FOCETRIA platform : Phase II, formulation, dosage and schedule of A(H1N1) ± MF59, adult/elderly (V111_02) HI titer ≥1:40 by day 42, by age group 18–60 years >60 years Subjects (% ± 95% CI) 0 20 40 60 80 100 Day 0 21 0 21 42 42 57% n= 126 120 122 126 120 122 117 117 CHMP criteria Novartis Vaccines data on file. Data from V111_02. 126 120 122 117 117 117 117 15 µg non-adj. 3.75 μ g + 50% MF59 7.5 μ g + 100% MF59
42. FOCETRIA platform : Phase II, formulation, dosage and schedule of A(H1N1) ± MF59, adult/elderly (V111_02) Seroconversion by day 42, by age group Subjects (% ± 95% CI) 0 20 40 60 80 100 Day 21 42 26% 18–60 years >60 years 21 42 n= 126 120 122 126 120 122 117 117 117 117 CHMP criteria Novartis Vaccines data on file. Data from V111_02. 15 µg non-adj. 3.75 μ g + 50% MF59 7.5 μ g + 100% MF59
43. FOCETRIA platform: Phase II, formulation, dosage and schedule of A(H1N1) ± MF59, adult/elderly (V111_02) HI GMT by day 42, by age group 50 100 150 200 250 300 350 400 450 0 Day 0 21 42 0 21 42 HI GMT ± 95% CI 18–60 years >60 years n= 126 126 120 122 117 117 120 122 Novartis Vaccines data on file. Data from V111_02. 126 120 122 117 117 117 117 15 µg non-adj. 3.75 μ g + 50% MF59 7.5 μ g + 100% MF59
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53. Vida Media (metodo 1 compartimiento) Pichichero, M. E. Gentile A et al. Pediatrics 2008;121:e208-e214 Edad Vida ½ (días) IC 95% Total 3.7 2.9-4.5 Rec Nac. 3.7 2.5-4.9 2 meses 2.0 1.3-2.6 6 meses 2.2 1.6-2.9
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Notas del editor
Se conocen 3 serotipos de virus influenza: A, B y C basadas en diferencias antigénicas entre sus nucleoproteínas (NP) y matrices proteicas (M). En el virus influenza A, se distinguen subtipos, basados en las características de sus proteínas de envoltura: hemaglutinina (H) y neuraminidasa (N).
Key messages: Vaccination with AFLUNOV led to rapid and statistically significant increases in antibody levels. AFLUNOV demonstrated superior immunogenicity compared to non-adjuvanted vaccine. Context: These data can be used to directly demonstrate that AFLUNOV can induce strong and durable immunity after primary immunisation. More detail: In this Phase II, randomized, controlled, observer-blind, single-center study, 40 adults were recruited to receive three doses of either AFLUNOV (n=14), 15 μg MF59-adjuvanted H5N1 vaccine (n=13) or 15 μg non-adjuvanted H5N1 vaccine (n=13). Two priming vaccinations were administered 3 weeks apart, followed by a 6 month booster dose. Data shown on the slide is for the AFLUNOV (n=14) and the 15 μg non-adjuvanted H5N1 vaccine (n=13) groups after the second priming dose. At 21 days following the second primary vaccination, subjects receiving MF59-adjuvanted vaccine reported statistically significant increases in microneutralization antibody titers ( P <0.01). AFLUNOV induced sustained antibody levels for 200 days (data not shown, but is present in the references). Following booster immunization (day 201), the MN titers sharply increased above baseline (data not shown, but is present in the references) for both groups receiving MF59-adjuvanted vaccines . ClinicalTrials. Gov Identifier: NCT00382187 Data from V87P2, Galli G et al . PNAS, 2009; in press.
Several factors affect the efficacy and effectiveness of influenza vaccines, notably the antigenic similarity between circulating strains and the recommended influenza vaccine strains. 1 The effect of mismatch between the circulating and vaccine influenza strains can be seen in a US randomized placebo-controlled trial of adults (18-64 years of age) during the 1997-1998 (n = 1184) and 1998-1999 (n = 1191) influenza seasons. During the 1997-1998 season, culture isolates containing influenza A were characterized as A/Sydney/5/97-like(H3N2) viruses, a strain antigenically distinct from the A/H3N2 strain contained in the seasonal vaccine. The resulting vaccine efficacy against serologically confirmed illness was 50%. In 1998-1999, however, the circulating strains – A/Sydney/5/97 (H3N2)-like and B/Beijing/184/93-like viruses – were similar to the vaccine viruses, yielding a vaccine efficacy of 86%. In order to account for changes in viral antigenicity due to antigenic drift, vaccine composition is reviewed annually, and modified as necessary to respond to antigenic drift. Annual vaccination is needed to maximize protection against currently circulating strains. References Bridges CB, Thompson WW, Meltzer MI, et al. Effectiveness and cost-benefit of influenza vaccination of healthy working adults: a randomized controlled trial. JAMA. 2000;284:1655-1663. Centers for Disease Control and Prevention (CDC) Interim Within-Season Estimate of the Effectiveness of Trivalent Inactivated Influenza Vaccine – Marshfield, Wisconsin, 2007-08 Influenza Season. 2008;57(15):393-398.
Blood samples taken to assess: antibody responses Safety and tolerability recorded: Immediately after each vaccination, on a diary card (<7 days post-vaccination)
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