1 / 15

National Vaccine Advisory Committee November 29, 2005

National Vaccine Advisory Committee November 29, 2005. Update on NIH H5N1 Vaccine Trials Linda C. Lambert Chief, Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/DHHS. H5 inactivated vaccine candidate. rg A/Vietnam/1203/04 (H5N1)

july
Download Presentation

National Vaccine Advisory Committee November 29, 2005

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. National Vaccine Advisory CommitteeNovember 29, 2005 Update on NIH H5N1 Vaccine Trials Linda C. Lambert Chief, Respiratory Diseases Branch Division of Microbiology and Infectious Diseases NIAID/NIH/DHHS

  2. H5 inactivated vaccine candidate • rg A/Vietnam/1203/04 (H5N1) • Basic amino acid sequence at cleavage site replaced by sequence of apathogenic avian virus (St. Jude’s CRH) • Egg-grown subunit vaccines without adjuvant, using current production • Formulated at 90 mcg and 30 mcg per mL,

  3. Evaluation of H5 vaccines: Objectives • Determine dose-related safety and immunogenicity • Gain experience with the logistical issues involved in producing a pandemic vaccine

  4. Initial evaluation of H5: DMID 04-063 • Product produced by Sanofi Pasteur for NIH • Subjects: Healthy adults ages 18 to 64 • Design: Prospective, randomized, double blind • Interventions: Two IM doses H5 vaccine separated by 28 days • Placebo, 7.5 mcg, 15 mcg, 45 mcg, 90 mcg • 1:2:2:2:2 randomization • Endpoints • Safety: solicited and unsolicited AEs • Immunogenicity: neutralizing titer of 1:40

  5. 04-063 Demographics (N=451)

  6. 04-063 Assessment of immune response • Sera collected on day 0 (pre dose 1), 28 (pre dose 2), 56 (28 days post dose 2), 180. • Microneutralization (MN) against vaccine seed virus in MDCK cells • Hemagglutination-inhibition (HAI) against vaccine seed virus using horse erythrocytes • Also tested for H3-specific antibody • Results available for stage I only

  7. DMID 04-063: Summary • Vaccine was well tolerated at all doses • Dose related local pain and tenderness • Some neutralizing responses seen at all doses • Best responses seen at two highest doses • HAI test using horse erythrocytes correlates well with neutralizing response

  8. H5N1 Vaccine TrialsDosage Sparing Approaches 1. Type of Vaccine - Whole virus vs. subunit >Baxter - Live vs. inactivated >LID/NIAID: Kanta Subbarao 2. Intradermal route 3. Inclusion of an adjuvant

  9. DOSAGE SPARINGIntradermal Immunization • Design: Phase I, randomized trial; subjects & investigators blinded to dosage level but not to route • Population: Healthy 18-49 years old • Vaccine: Inactivated rg A/Vietnam (H5N1) Two formulations: 30µg and 90µg/mL • Study Groups (N=25/group): Intradermal - 3µg or 9µg in 0.1mL Intramuscular - 15µg or 45µg in 0.5mL Patel S, et. al., study in progress at BCM.

  10. STUDY PROCEDURES • Vaccination on Day 0 and Day 28 • Reactogenicity Assessments • Clinic visits Days 1, 2, and 7 after each vaccine dose; symptoms/signs recorded daily for 7 days; 6-month SAE follow-up • Immunogenicity Assessments • Serum HAI and neutralizing antibody levels to be assayed on samples collected before dose 1, 1 month after each dose, and 6 months after dose 2.

  11. PRIMARY ENDPOINTS • Adverse events (AE) or serious adverse events (SAE) solicited in-clinic and via memory aids and periodic targeted physical assessments • Proportion of subjects in each vaccine group achieving a serum neutralizing antibody titer of 1:40 against the influenza A/H5N1 virus on Day 56

  12. REACTOGENICITY • IM Groups – Occasional erythema observed; usually resolved in 1-2 days • ID Groups – Erythema and induration lasting 3-5 days; occasional faint pigmentation at injection site • No severe vaccine- associated adverse events

  13. PROGRESS TO DATE • All 100 subjects completed the 56 day follow up • HAI and Neut immunoassays; results in December • Follow-up visit scheduled for day 206

  14. Dose SparingInclusion of Adjuvants • HHS and NIH are supporting several manufacturers to produce adjuvanted H5N1 vaccines for clinical testing by the NIH • Trials will assess safety and whether adjuvants improve the immunogenicity of influenza vaccines Aluminum hydroxide adjuvanted H5N1 vaccines: • Sanofi Pasteur (under HHS contract); Q12006 • Chiron (also MF59); Q12006 • Baxter (cell based/whole virus); Q22006 • IDBiomedical (GSK) NIH grant (cell based); 1 year +

  15. NIH Vaccine Evaluation Units • Baylor College of Medicine • Cincinnati Children’s Hospital • St. Louis University • UCLA Harborview Medical Center • University of Maryland • University of Rochester • Vanderbilt University

More Related