A colorized transmission electron micrograph of influenza A virus particles, colorized orange, isolated from a patient sample and then propagated in cell culture. NIAID
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Flu vaccines were first produced for the military in the 1940s - but despite 80+ years of research and refinement (e.g. cell culture-propagated vaccines , adjuvanted and high dose vaccines, quadrivalent formulas, etc.) - most years they still only provide moderate protection against influenza infection, and are pretty much `strain-specific'.
The holy grail of vaccinology is the creation of a `Universal Flu Vaccine', a goal that has been described for decades as being `five years away'. A statement that still holds true today.
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 sub-types. While ideal, the current goal is a bit more modest.
Despite these reduced goals, the road to a universal flu shot is a long one, and success - at least in the near term - is far from guaranteed (see Scripps Research: Study Suggests Some Flu Viruses May Be Less Susceptible To A `Universal' Flu Vaccine).
Most of these clinical trials have involved quadrivalent influenza vaccines (QIVs), but late last week the NIH announced they were beginning clinical trials on a hexavalent `universal' flu vaccine, built off 6 virus components.
Influenza A:
- H1: A/Idaho/07/2018
- H2: A/Singapore/1/1957
- H3: A/Perth/1008/2019
- H3: A/Darwin/106/2020
Influenza B:
- B/Victoria lineage: B/Colorado/06/2017
- B/Yamagata lineage: B/Phuket/3073/2013
Although hexavalent childhood vaccines (e.g. DTaP-IPV-Hib-HepB) have been around for years, this appears to be new territory for influenza vaccines.
Interesting, this study will incorporate an H2 A/Singapore/1/1957 virus, which famously sparked the 1957 pandemic, and hasn't been seen in humans since 1968.
H2 viruses continue to circulate in birds, swine, and other mammals (see below), and are regarded as a plausible source of a future pandemic.
- In 2017, in H2N2: Everything Old Is Flu Again, we saw a study published in The Journal Of Veterinary Medical Science, which detailed the finding of H2N2 in Siberian Muskrats. (see Genetic characterization of an H2N2 influenza virus isolated from a muskrat in Western Siberia).
- In 2016's A Novel Reassortant H2N8 In China, described an H2N8 avian flu virus was isolated from a domestic duck in Zhejiang Province, Eastern China, in 2013.
- In 2006 and early 2007, a reassorted H2N3 subtype was detected in pigs on two different Missouri farms, which was the first known appearance of an H2 virus in a mammal since it was supplanted by the H3N2 virus in 1968 (see CIDRAP On Mutated Swine Flu Virus).
This clinical trial (ID CT05968989) is expected to run through the end of 2024. The NIH's press release follows.
NIH clinical trial of universal flu vaccine candidate begins
Vaccine targets six flu strains.
Enrollment in a Phase 1 trial of a new investigational universal influenza vaccine candidate has begun at the National Institutes of Health’s Clinical Center in Bethesda, Maryland. The trial is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, and will evaluate the investigational vaccine for safety and its ability to elicit an immune response.
Currently available seasonal influenza (or “flu”) vaccines are effective at preventing specific strains of influenza. Each year, the vaccines are re-evaluated and changed to best match the strains of flu predicted to be the most dominant in the upcoming flu season. Most seasonal flu vaccines are designed to train the immune system to defend against three or four different common strains of flu, but a “universal” influenza vaccine might someday provide protection against many more.
“An ideal universal influenza vaccine could be taken less frequently than once a year and protect against multiple strains of influenza virus. With each new universal influenza vaccine candidate and clinical trial, we take another step closer to that goal,” said Acting NIAID Director Hugh Auchincloss, M.D.
The vaccine candidate under investigation, FluMos-v2, was designed by researchers at NIAID’s Vaccine Research Center (VRC). It is an adaptation of an earlier universal flu vaccine candidate, FluMos-v1, which began first-in-human testing in 2021 and is still undergoing trials. FluMos-v2 is designed to induce antibodies against many different influenza virus strains by displaying part of the influenza virus hemagglutinin (HA) protein in repeating patterns on self-assembling nanoparticle scaffolds. Exposure to these harmless fragments of virus proteins prepares the immune system to recognize and fight the actual virus. When tested in animals, the experimental vaccine resulted in robust antibody responses.
While the FluMos-v1 vaccine candidate displays HA from four strains of influenza virus, FluMos-v2 displays HA from six: four influenza A viruses and two influenza B viruses. The researchers anticipate that this will further broaden vaccine recipients’ immunity, providing protection against a wider variety of influenza viruses.
The new clinical trial is expected to enroll 24 healthy volunteers, aged 18-50 years, who will receive two intramuscular injections of the FluMos-v2 vaccine candidate. These injections will be given 16 weeks apart. At first, participants will be enrolled in the lower dose group (60 mcg per vaccination). If no safety concerns are identified after at least three participants have received this dose, enrollment will begin in the higher dose (180 mcg per vaccination) group. The study team plans to enroll 12 participants into each dosage group.
For 40 weeks after their first vaccination, participants will receive regular follow-up phone calls and examinations to track their responses to the experimental vaccine. Blood samples will be taken during study visits to measure any immune responses to the vaccine candidate.
Further information about the trial is available at clinicaltrials.gov using the identifier NCT05968989.
