#14,802
There are a lot of things we think we know about influenza, and its interactions with our immune system, that - for reasons we don't always understand - don't always work out the way the way that we expect.
A long standing assumption is that once you are naturally infected with a specific influenza virus, you will carry lifelong - or at least long-lasting - antibody titers that are protective against that specific virus.Similar, but potentially less long-lasting effects are also expected from vaccination. This `acquired immunity' is also expected to extend to antigenically similar viruses, although things get much murkier once even minor changes to the virus are introduced.
Last spring, in a fascinating research study conducted by researchers at the NIH and NIAID (see C.I.D.: Influenza A Reinfection in Sequential Human Challenge), we saw that this wasn't necessarily so.
In that study, researchers exposed a small group of healthy volunteers to a specific H1N1 virus, and recorded their subsequent infections and immune responses.
A year later, they repeated this virus challenge on the same group (n=7) with the exact same virus, expecting their residual immunity would protect them. To their surprise they found that at least 3 - and possibly 5 - of the 7 were reinfected with the exact same flu strain.While pre-existing antibody titers against specific influenza virus strains are undoubtedly linked to immunity, the requisite levels, their persistence over time, and their effectiveness in preventing infection are far from fully understood.
There are also other, poorly understood factors, such as recent research which has suggested the influenza HA Group type you are first exposed to makes a significant, and lasting, impression on your immune system (see Nature: Declan Butler On How Your First Bout Of Flu Leaves A Lasting Impression).In an attempt to unravel some of these mysteries, the NIH has begun a new clinical trial where healthy adult volunteers will be inoculated with an engineered variant of the 2009 H1N1 virus (InfluenzaA/Bethesda/MM2/H1N1), and monitored in a clinical setting for at least 7 days, with follow-ups over a period of 3 months.
First, the press release from the NIH which includes a link to the clinical study, then I'll return with a brief postscript.
Influenza Human Challenge Study Begins at NIAID-Sponsored Clinical Trial Units
October 23, 2019
A clinical trial in which healthy adults will be deliberately infected with influenza virus under carefully controlled conditions is recruiting volunteers at four Vaccine and Treatment Evaluation Units (VTEUs) supported by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). One study aim is to assess how levels of pre-existing influenza antibodies impact the timing, magnitude and duration of a volunteer’s flu symptoms following exposure to influenza virus.
The first doses of challenge virus were administered to five volunteers earlier this week. Up to 80 people aged 18 to 50 years will be enrolled in the trial. The study builds on recent work by scientists in the NIAID Laboratory of Infectious Diseases to develop a model of influenza disease with controlled human infection studies.
“NIAID investigators have been pioneers in contemporary human influenza challenge trials,” said NIAID Director Anthony S. Fauci, M.D. “These trials provide a powerful tool to study many aspects of influenza disease progression and also can help to efficiently assess new treatments and vaccine candidates.”
He added: “Expanding the capacity to perform human challenge trials is a key goal in NIAID’s strategic plan to support the development of vaccines that confer broad and durable protection against influenza. This new trial at the VTEUs will help us achieve that goal.”
Volunteers will receive a nasal spray containing a strain of seasonal influenza virus made under good manufacturing practice conditions. The challenge virus, InfluenzaA/Bethesda/MM2/H1N1, was developed by NIAID scientists and reliably produces mild to moderate influenza disease in most recipients. It has been administered to approximately 400 participants in four previous influenza challenge trials conducted at the NIH Clinical Center in Bethesda, Md. No significant safety issues or severe or complicated cases of influenza occurred, and no transmission of the virus outside of the clinic was seen during the earlier trials.
In the current trial, volunteers will remain in the clinic for at least seven full days after being challenged with the virus. Blood samples and nasal and throat swabs taken before and periodically after viral challenge will be used to trace the initiation, size and duration of various immune system responses, and to detect virus shedding. The appearance and resolution of flu symptoms, such as fever and muscle aches and weakness, will be recorded daily by the volunteers and study staff for a total of 14 days after the virus challenge. All volunteers will be followed for approximately 90 days post-challenge and will have additional blood and nasal wash samples taken at several follow-up clinic visits.
Preliminary trial results are expected in May 2020.
The lead VTEU site is the University of Maryland School of Medicine, Baltimore, where Kathleen Neuzil, M.D., is principal investigator. Other VTEUs conducting the trial, and lead investigators at each, are:
Cincinnati Children’s Hospital Medical Center (David Bernstein, M.D.)Additional information about the trial, H1N1v Virus Challenge Study in Healthy Subjects, is available at ClinicalTrials.gov using the identifier NCT04044352.
Duke University (Christopher Woods, M.D.)
Saint Louis University Center for Vaccine Development (Daniel Hoft, M.D., Ph.D.)
Unless and until we can better understand the human immune system - and how it interacts with numerous exposures to a wide array of seasonal and novel flu viruses - the prospects for developing an effective and long lasting universal flu vaccine are diminished.
Dubbed the `holy grail' of immunology, a universal flu vaccine is often described in the popular press as being a `one time (or every few years) shot' that would convey nearly full protection against all flu subtypes.As it is, the immediate goal for a `universal' vaccine is a bit more realistic; a 75%+ VE (Vaccine Effectiveness) across multiple (seasonal & novel) subtypes that would last at least a year (see J.I.D.: NIAID's Strategic Plan To Develop A Universal Flu Vaccine).
Hopefully, the results from this NIH study will get us closer to that goal.
