NIH begins first human trial of universal vaccine candidate against influenza

The first clinical trial of an innovative universal influenza vaccine focuses on the safety and tolerability of the vaccine, as well as its ability to induce an immune response in healthy volunteers. Scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have developed the experimental vaccine, called H1ssF_3928.

H1ssF_3928 is designed to teach the body how to generate a protective immune response against various subtypes of influenza by concentrating the immune system on a portion of the virus that varies relatively little from one strain to the other . The candidate vaccine was developed as part of a broader research program to create a so-called "universal" influenza vaccine that provides long-term protection for all age groups against -types of influenza, including those likely to cause a pandemic.

Anthony S. Fauci, Director of NIAID, said, "Seasonal influenza is an ongoing challenge for public health and we are continually faced with the possibility of a pandemic influenza resulting from the emergence and spread of new viruses. of the flu. This Phase 1 clinical trial is a step forward in our efforts to develop a universal, broadly protective, long-lasting influenza vaccine. "

The clinical trial is conducted at the NIH Clinical Center in Bethesda, Maryland. It is led by Grace Chen, M.D., of the NIAID Vaccine Research Center (VRC) Clinical Trials Program. The trial will progressively include at least 53 healthy adults aged 18 to 70 years old. The first five participants will be 18 to 40 years old and will receive a single intramuscular injection of 20 micrograms (mcg) of the experimental vaccine. The remaining 48 participants will receive two 60-μg vaccinations spaced 16 weeks apart. They will be stratified by age into four groups of 12 people: 18 to 40, 41 to 49, 50 to 59 and 60 to 70. Investigators hope to understand how the immune response of experimental vaccine participants may vary with age and the likelihood of their prior exposure to different influenza variants.

Participants in the study will be asked to record their temperature and symptoms on a diary for one week after each injection. They will also be asked to come to the clinic to provide blood samples at different times. Investigators will badyze the samples at the laboratory to characterize and measure levels of anti-influenza antibodies, potentially indicative of immunity against influenza. Participants will return for 9 to 11 follow-up visits over a period of 12 to 15 months. They will not be exposed to any influenza virus as part of the clinical trial.

John Mascola, director of CRV, said, "This Phase 1 clinical trial is the culmination of years of research and development made possible by the unique collaborative framework that CRV offers by bringing together scientists from a high level of expertise, manufacturing expertise and an exceptional clinical team.

A team of scientists from the CRV has developed the prototype universal vaccine against influenza. It presents part of the hemagglutinin (HA), an influenza protein, on the surface of a microscopic nanoparticle made of non-human ferritin. Ferritin is a natural protein found in the cells of all living species. It is useful as a vaccine platform because it forms particles that can display multiple peaks of influenza AH on its surface, mimicking the natural organization of AH on the virus. ; influenza.

The HA, which allows the influenza virus to enter a human cell, is composed of a region of the head and stem. The body can develop an immune response to both regions, but most of the response is directed to the head. Influenza vaccines need to be updated every year because the AH's head is constantly changing – a phenomenon called "antigenic drift." The new candidate vaccine consists only of an AH stem. The stem is more constant than the head among flu strains and is therefore less likely to be updated each season. Many scientists predict that targeting the AH stem without the distraction of the AH head could induce broader and more lasting immunity.

Scientists have used the stem of an H1N1 flu virus to create the candidate vaccine. H1 is the subtype HA of the virus and N1 is the subtype neuraminidase (or NA, another surface protein of the flu). Although there are 18 subtypes of HA and 11 known AN subtypes, only H1N1 and H3N2 viruses circulate among people seasonally. However, strains H5N1 and H7N9 and other strains have been the cause of some deadly epidemics and are likely to cause a pandemic if they become more easily transmitted.

This H1N1 candidate vaccine protected animals from H5N1 infection, a different influenza subtype, indicating that the antibodies induced by the vaccine could protect against other influenza subtypes of the "flu" group. 1 ", comprising both H1 and H5. In future clinical trials, the CRV plans to evaluate a vaccine designed to protect against "group 2" influenza subtypes, which include H3 and H7.

Initial data from a previous CVR clinical trial evaluating a ferritin nanoparticle-based vaccine including both the head and haemagglutinin stem showed that the platform is safe and well tolerated at home. l & # 39; man. As with all clinical trials, a protocol safety review team will regularly review study data to monitor the safety of participants in this phase 1 study.

The CRV expects the clinical trial to be completed by the end of 2019 and hopes to begin reporting on results in early 2020