VRC 307: A Double-Blind, Randomized Phase I Study of the Safety and Immunogenicity of a Prime-Boost Schedule of the Investigational DNA Trivalent Influenza Vaccine, VRC-FLUDNA047-00-VP, Followed by the 2008/2009 Seasonal Influenza Trivalent Inactivat...

Summary

Objectives: * To evaluate the safety and tolerability of a prime-boost study regimen that includes the recombinant DNA vaccine followed by licensed 2008/2009 FluLaval(Registered Trademark) in adults ages 18-50 years and adults ages 51-70 years as compared with control groups that receive the licensed vaccine only. * To evaluate whether the study participants in each age group receiving a prime-boost schedule have a greater frequency of H1 or H3 neutralizing antibodies compared with those of the same age group who received only the 2008/2009 trivalent influenza vaccine. * To evaluate differences in antibody or T cell responses (quantity, quality, or durability) between the two groups. Eligibility: * Participants ages 18 to 70 years of age who are available for clinic follow-up through Week 24 and who have no previously undiagnosed clinically significant chronic diseases. Participants will provide blood samples for further testing to determine eligibility. Females must not be or become pregnant during the study. * Volunteers who have been immunized with the current season FDA-approved influenza vaccine (2008-2009), or who are being treated for tuberculosis may not participate. Design: * The study lasts for 24 weeks. * Week 0: The first day of Week 0 (i.e., Day 0) is defined as the day of enrollment and first injection. Specific eligibility is reviewed. Participants will receive an injection of either the DNA vaccine VRC-FLUDNA047-00-VP (at 4 mg dosage) or a placebo. * Week 4: All study participants will receive an injection of the trivalent seasonal influenza vaccine, according to the manufacturer's package insert directions. * Participants will be given 7-day diary cards on which to record temperature and symptoms (e.g., muscle aches, headache, chills, nausea) and injection site reactions (e.g., pain, tenderness). Participants may also enter this information via the Internet. Presence of symptoms may require additional visits to the clinic. * Participants will return to the clinic 2 weeks after each injection for the following procedures: * Blood draws for further tests to determine the immune system's response to the vaccine(s) Clinical evaluations: vital signs and weight, examinations of the lymph nodes, and targeted physical exam on any visit if indicated by interim complaints or laboratory findings.

Timeline

Start

2009-03-03

Primary completion

2010-06-21

Completion

2010-06-21

Publications

• Background Subbarao K, Murphy BR, Fauci AS. Development of effective vaccines against pandemic influenza. Immunity. 2006 Jan;24(1):5-9. doi: 10.1016/j.immuni.2005.12.005.
• Background Luke CJ, Subbarao K. Vaccines for pandemic influenza. Emerg Infect Dis. 2006 Jan;12(1):66-72. doi: 10.3201/eid1201.051147.
• Background Beigel JH. Influenza. Crit Care Med. 2008 Sep;36(9):2660-6. doi: 10.1097/CCM.0b013e318180b039.
• Ledgerwood JE, Hu Z, Costner P, Yamshchikov G, Enama ME, Plummer S, Hendel CS, Holman L, Larkin B, Gordon I, Bailer RT, Poretz DM, Sarwar U, Kabadi A, Koup R, Mascola JR, Graham BS; VRC 307 and VRC 309 Study Teams. Phase I clinical evaluation of seasonal influenza hemagglutinin (HA) DNA vaccine prime followed by trivalent influenza inactivated vaccine (IIV3) boost. Contemp Clin Trials. 2015 Sep;44:112-118. doi: 10.1016/j.cct.2015.08.006. Epub 2015 Aug 12.
• Enama ME, Hu Z, Gordon I, Costner P, Ledgerwood JE, Grady C; VRC 306 and 307 Consent Study Teams. Randomization to standard and concise informed consent forms: development of evidence-based consent practices. Contemp Clin Trials. 2012 Sep;33(5):895-902. doi: 10.1016/j.cct.2012.04.005. Epub 2012 Apr 20.

Drugs

Indications