First human trial of universal influenza vaccine underway

Researchers are currently conducting the first human trial of a universal flu vaccine candidate, the National Institutes of Health (NIH) announced on April 3.

The NIH's National Institute of Allergy and Infectious Diseases (NIAID) hopes to develop a vaccine that will overcome the difficulties associated with seasonal changes among strains of influenza.

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

The test will examine the safety and tolerability of the vaccine (H1ssF_3928) as well as its immunogenicity in healthy volunteers.

The vaccine stimulates protective immune responses against very different influenza subtypes by installing in a relatively constant area of ​​the virus from one strain to the other. The development of the vaccine candidate is part of a broader initiative to develop a universal vaccine candidate capable of providing long-lasting protection to individuals of all ages and against several subtypes of influenza, including those likely to cause a pandemic.

Grace Chen, MD, of the NIAID Vaccine Research Center's (VRC) clinical trial program, is leading the study at the NIH Clinical Center in Bethesda, Maryland. The trial will progressively include at least 53 healthy adults aged 18 to 70 years. The first five participants, aged 18 to 40 years old, will receive a small intramuscular injection (20 μg) of the vaccine to verify its safety.

The remaining 48 participants will receive two injections of 60 μg spaced 16 weeks apart; These participants will be stratified into four age groups of 12 participants: 18 to 40, 41 to 49, 50 to 59 and 60 to 70. Researchers will investigate whether and to what extent their immune responses vary with age and the likelihood of their previous exposure to different influenza variants.

Participants will document their temperature and onset of symptoms for one week after each injection. They will not be exposed to influenza as part of the study, but will periodically provide blood samples that will be tested to characterize and measure levels of anti-influenza antibodies. Nine to 11 follow-up visits will be made over a 12 to 15 month period.

"This Phase 1 clinical trial is the culmination of years of research and development made possible by the unique collaborative framework offered by the CRV by bringing together high-level scientists, manufacturing expertise and a team of experts. exceptional clinic, "said CRV Director John Mascola, MD. in the press release.

More sustainable immunity

"A team of scientists from CRV has developed the prototype universal influenza vaccine, presenting part of hemagglutinin (HA), an influenza protein, on the surface of a microscopic nanoparticle. ferritin is a natural protein found in the cells of the human body According to the press release, it is useful as a vaccine platform, because it forms particles that can display multiple spikes of HA on its surface , thus mimicking the natural organization of HA on the influenza virus.

HA allows the flu virus to pass into a human cell; it contains a region of head and stem. Although the body can develop an immune response against both regions, most of it is focused on the head. The HA head changes or constantly undergoes "antigenic drift"; therefore, the new vaccine candidate contains only the HA stem, which makes it less likely to need an update each season. By focusing on the HA stem, the researchers believe that the new vaccine candidate could provide broader and longer-lasting immunity.

To create the vaccine candidate, researchers used the stem of an H1N1 flu virus. H1 describes the HA subtype of the virus and N1 describes the neuraminidase subtype. (Neuraminidase, or NA, is another surface protein of influenza.) Eighteen subtypes of HA and 11 subtypes of NA are currently known; However, only H1N1 and H3N2 viruses circulate in humans on a seasonal basis. The H5N1 and H7N9 viruses and other strains have caused some deadly outbreaks and could potentially cause a pandemic if they can spread more easily.

The fact that the H1N1 candidate vaccine has been effective against H5N1 infection – a different influenza subtype – suggests that the antibodies induced by the vaccine may protect against other subtypes. "Group 1" influenza, including H1 and H5. Future clinical trials will evaluate a vaccine against "Group 2" influenza subtypes, including H3 and H7.

An earlier trial on the CVR of a ferritin nanoparticle-based vaccine including both the head and hemagglutinin stem showed that the platform was safe and well tolerated when it was used in the man. In accordance with all clinical trials, a protocol safety review team will systematically evaluate vaccine safety data in Phase 1 study participants.

The test registration is expected to be completed by the end of 2019 and the results are expected by the beginning of 2020. Additional information is available at ClinicalTrials.gov (NCT03814720). ).

Follow Medscape on Facebook, Twitter, Instagram and YouTube.