In 2008, Acambis announced work on a universal flu vaccine (ACAM-FLU-ATM) based on the less variable M2 protein component of the flu virus shell. See also H5N1 vaccines.
In 2009, the Wistar Institute in Pennsylvania received a patent for using "a variety of peptides" in a flu vaccine, and announced it was seeking a corporate partner.
In 2010, the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. NIH announced a breakthrough; the effort targets the stem, which mutates less often than the head of the viral HA.
By 2010 some universal flu vaccines had started clinical trials.
* BiondVax identified 9 conserved epitopes of the influenza virus and combined them into a recombinant protein called Multimeric-001. All seven of Biondvax's completed phase 2 human trials demonstrated safety and significant levels of immunogenicity. More recently, Biondvax undertook a two-year, phase 3 study of Multimeric-001, its candidate universal influenza vaccine. In October 2020, results of the phase 3 study were published, indicating no apparent efficacy.
* ITS's fp01 includes 6 peptide antigens to highly conserved segments of the PA, PB1, PB2, NP & M1 proteins, and has started phase I trials.
DNA vaccines, such as VGX-3400X (aimed at multiple H5N1 strains), contain DNA fragments (plasmids). Inovio's SynCon DNA vaccines include H5N1 and H1N1 subtypes.
Other companies pursuing the vaccine as of 2009 and 2010 include Theraclone,  VaxInnate, Crucell NV, Inovio Pharmaceuticals, Immune Targeting Systems (ITS) and iQur.
In 2019, Distributed Bio completed pre-clinical trials of a vaccine that consists of computationally selected distant evolutionary variants of hemagglutinin epitopes and is expected to begin human trials in 2021.
In recent years, research has concerned use of an antigen for the flu hemagglutinin (HA) stem.
Based on the results of animal studies, a universal flu vaccine may use a two-step vaccination strategy: priming with a DNA-based HA vaccine, followed by a second dose with an inactivated, attenuated, or adenovirus-vector-based vaccine.
Some people given a 2009 H1N1 flu vaccine have developed broadly protective antibodies, raising hopes for a universal flu vaccine.
A vaccine based on the hemagglutinin (HA) stem was the first to induce "broadly neutralizing" antibodies to both HA-group 1 and HA-group 2 influenza in mice.
In July 2011, researchers created an antibody, which targets a protein found on the surface of all influenza A viruses called haemagglutinin.
 FI6 is the only known antibody that binds (its neutralizing activity is controversial) to all 16 subtypes of the influenza A virus hemagglutinin and might be the lynchpin for a universal influenza vaccine. The subdomain of the hemagglutinin that is targeted by FI6, namely the stalk domain, was actually successfully used earlier as universal influenza virus vaccine by Peter Palese's research group at Mount Sinai School of Medicine.
Other vaccines are polypeptide based.