Seasonal influenza kills hundreds of thousands of people every year due to a constantly changing virus and highly inefficient vaccine production. A universal flu vaccine could deal with the first problem, and mRNA technology with the second.
One of the first clinical trials of an experimental flu vaccine that works against most, if not all, strains of flu recently yielded positive results, and a new study of a similar vaccine — this one using mRNA technology — just began enrolling volunteers.
Creating a universal influenza vaccine has long been vaccinologists’ dream.
Seasonal flu kills an estimated 400,000 people annually worldwide, most of them old or very young. Annual U.S. deaths over the past decade ranged from roughly 12,000 to 52,000, depending on the severity of disease caused by that season’s main strain, except during the COVID-19 pandemic when social distancing and other factors resulted in lower flu mortality.
Uptake of flu vaccines is low, largely because a new shot or nasal spray is needed every year due to the influenza virus’s ability to change slightly but far more frequently than most other viruses.
The production process is cumbersome and slow. Scientists make educated guesses about which of the influenza strains circulating during South Asia’s summer monsoon season are likely to out-compete the others in the West the following winter. Those three or four strains are then grown in fertilized eggs for use in the seasonal flu vaccines.
The scientists’ predictions are not always accurate. Sometimes there’s a poor match between some of the strains in the vaccine and the strains that circulate in the United States during that flu season.
A universal vaccine against most strains of flu would take much of the guesswork out of flu vaccination and could confer longer-lasting protection, so the annual flu shot would be a thing of the past.
Scientists at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC) designed an experimental non-RNA vaccine, known as H1ssF, to elicit immunity against a broad range of viruses. A phase I clinical trial of 52 volunteers found that it was safe, well-tolerated and induced broad antibody responses, according to two research articles published last monthin Science Translational Medicine by first authors Sarah F. Andrews, Ph.D., staff scientist, and Alicia T. Widge, M.D., staff clinician and associate chief for clinical research and development, and their VRC colleagues.
Messenger RNA was discovered only in the 1960s, and the first vaccine to use it was against Ebola in Africa, a target population so small that there was no commercial development in the U.S. The first mRNA vaccines to win approval from the FDA were the Pfizer and Moderna vaccines against COVID-19. They were highly effective and produced in record time, no eggs required.
Using this technology for a universal flu vaccine could provide many benefits.
The early-stage clinical trial that just began enrolling 50 healthy adults at Duke University School of Medicine in Durham, N.C. will test a new vaccine, also developed at NIAID, that is similar to the universal influenza vaccine described in the recently published papers. But this investigational vaccine, manufactured at the Duke Human Vaccine Institute, uses an mRNA platform.
ClinicalTrials.gov describes the H1ssF-3928 mRNA-LNP trial as consisting of three sequential groups of 10 participants each who will receive single low, medium or high doses, with pauses in between groups to evaluate safety. A fourth group will get an “optimal dose” based on data from the first three.
A fifth group will receive the current quadrivalent seasonal influenza vaccine so that researchers can compare immunogenicity and safety and, secondarily, efficacy. Participants will be followed for up to a year after vaccination to measure how long the immune response lasts and whether it remains effective over time as the virus continues to undergo small changes, known as drifts.
"This is an exciting moment,” principal investigator Emmanuel “Chip” Walter, M.D., chief medical officer of the Duke Human Vaccine Institute and director the Duke Vaccine and Trials Unit. “As we continue to test additional vaccine candidates, we move closer to the ultimate goal of modernizing the flu vaccine in a way that provides better, longer-lasting protection against a virus that kills hundreds of thousands of people worldwide each year.”
As big a killer as seasonal influenza is — to say nothing of the misery endured by multitudes who are laid up in bed by the disease — the possibility of a bird flu pandemic caused by a virus against which no humans have any immunity is much scarier.
“The hope for a universal vaccine,” Walter said in an emailed response to questions from Managed Healthcare Executive, “is to include coverage against avian influenza strains.”