Influenza HA Ferritin Vaccine, Alone or in Prime-Boost Regimens With an Influenza DNA Vaccine in Healthy Adults

Summary

Background: Influenza, or "flu", is a very common infectious respiratory disease. Researchers want to develop a vaccine against flu. Vaccines teach the body to fight or prevent an infection. When the body learns to fight an infection, this is called an immune response. In this study, researchers want to test two new vaccines to help the body make an immune response to flu. Subjects received the vaccine injections in the upper arm muscle. One vaccine, the influenza HA Ferritin vaccine (HA-F A/Sing), was given to all subjects with a needle injection. The other vaccine, influenza DNA vaccine (DNA A/Sing), was given to subjects in Group 3 by a needle-free device that uses high pressure to push the vaccine through the skin and into the muscle. Objective: To test the safety and side effects of two new vaccines for prevention of H2 influenza (flu). Eligibility: Part I: Healthy adults ages 18-47 born after 1969. Part II: Healthy adults ages 18-70, but not born in 1966-1969. Design: Volunteers were tested for eligibility in a separate screening protocol. In Part I, all subjects received injections of HA Ferritin vaccine. These subjects were not expected to have H2N2 exposure based on their age and when H2N2 last circulated in the population. Five subjects in Group 1 received one injection of 20 mcg dose vaccine at Day 0 to test if it is safe. Then, five additional subjects in Group 2 received a total of two injections of a 60 mcg dose on Day 0 and 16 weeks later. In Part II, responses were evaluated from adults born before 1966 who may have prior potential exposure to H2N2 influenza as well as adults similar to those enrolled in Part I who are not expected to have H2N2 exposure. Also, Part II compared responses to 2 different vaccine regimens. Group 3 subjects received a DNA influenza vaccine prime at Day 0 and the HA Ferritin vaccine boost 16 weeks later. Group 4 subjects received the HA Ferritin vaccine 2 times, on Day 0 and 16 weeks later.

Timeline

Start

2017-10-25

Primary completion

2019-09-03

Completion

2019-09-03

Publications

• Background Kanekiyo M, Wei CJ, Yassine HM, McTamney PM, Boyington JC, Whittle JR, Rao SS, Kong WP, Wang L, Nabel GJ. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature. 2013 Jul 4;499(7456):102-6. doi: 10.1038/nature12202. Epub 2013 May 22.
• Background Yamashita I, Iwahori K, Kumagai S. Ferritin in the field of nanodevices. Biochim Biophys Acta. 2010 Aug;1800(8):846-57. doi: 10.1016/j.bbagen.2010.03.005. Epub 2010 Mar 12.
• Background Nabel GJ, Wei CJ, Ledgerwood JE. Vaccinate for the next H2N2 pandemic now. Nature. 2011 Mar 10;471(7337):157-8. doi: 10.1038/471157a. No abstract available.
• Andrews SF, Raab JE, Gorman J, Gillespie RA, Cheung CSF, Rawi R, Cominsky LY, Boyington JC, Creanga A, Shen CH, Harris DR, Olia AS, Nazzari AF, Zhou T, Houser KV, Chen GL, Mascola JR, Graham BS, Kanekiyo M, Ledgerwood JE, Kwong PD, McDermott AB. A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination. Nat Med. 2022 Feb;28(2):373-382. doi: 10.1038/s41591-021-01636-8. Epub 2022 Feb 3.
• Houser KV, Chen GL, Carter C, Crank MC, Nguyen TA, Burgos Florez MC, Berkowitz NM, Mendoza F, Hendel CS, Gordon IJ, Coates EE, Vazquez S, Stein J, Case CL, Lawlor H, Carlton K, Gaudinski MR, Strom L, Hofstetter AR, Liang CJ, Narpala S, Hatcher C, Gillespie RA, Creanga A, Kanekiyo M, Raab JE, Andrews SF, Zhang Y, Yang ES, Wang L, Leung K, Kong WP, Freyn AW, Nachbagauer R, Palese P, Bailer RT, McDermott AB, Koup RA, Gall JG, Arnold F, Mascola JR, Graham BS, Ledgerwood JE; VRC 316 Study Team. Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial. Nat Med. 2022 Feb;28(2):383-391. doi: 10.1038/s41591-021-01660-8. Epub 2022 Feb 3.

Drugs

Indications