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Universal Vaccines: Hope for the Future

By Amesh A. Adalja, MD, May 28, 2010

While vaccines have proven invaluable in the quest to control infectious diseases, certain microbes—exemplified by the influenza virus—have defied long lasting control because their antigenic structure mutates, creating moving targets for vaccines. For years, researchers have sought to develop an influenza vaccine that could be given once (or at least infrequently) and that would provide protection from all or most strains of influenza. Such a “universal vaccine” could greatly limit the disease burden of seasonal influenza and reduce the threat of an influenza pandemic.

In the April 2010 issue of the journal mBio, Cassone and Rappuoli review the topic of universal vaccinations for influenza and several other infectious diseases. Asserting the importance of this approach in controlling infectious diseases, the authors call for further development of universal vaccines.

Influenza Virus Exemplifies Need for Universal Vaccine

Each year as influenza season approaches, the seasonal flu vaccine is refined to best match the strains predicted to be circulating during that season. The vaccine is often a good match, but there have been occasions when mismatches occur, resulting in more widespread disease secondary to decreased vaccine efficacy. Mismatches also can have the long lasting effect of diminished confidence in the flu vaccine.

The emergence of a pandemic strain, as in 2009, necessitates the rapid development, manufacture, and distribution of a novel vaccine. While some influenza vaccines provide limited cross-reactivity between some strains, which may be boosted by adjuvants; however, this cross-reactivity is hardly a universal vaccine.

The search for a universal influenza vaccine is currently focused on identifying a structure that is present in all influenza strains and is not affected by antigenic shift and drift. Such a structure is coded for by a “conserved domain” of the virus’s genome. To date, several targets have been discovered:

  • Stalk of the hemagglutinin molecule

  • Nonglobular portion of the hemagglutinin molecule close to or containing the fusion peptide

  • Nucleoprotein

  • M2 protein

Restricted and Unrestricted Universal Vaccines

Cassone and Rappuoli divide universal vaccines into 2 broad conceptual categories:

  • Restricted—directed against related microbes (eg, influenza, pneumococcus)

  • Unrestricted—may be effective against genetically disparate microbes (eg, a vaccine targeted both S. aureus and E. coli)

Fascinating examples of vaccines with unrestricted universality are discussed, including the unrestricted vaccine mentioned above, which targets poly-N-acetylglucosamine and is protective against the gram negative bacterium E. coli and the gram positive bacterium S. aureus. Other approaches in development include a vaccine that is protective against both Candida and Aspergillus and a vaccine that targets the prokaryote bacterium S. aureus as well as the eukaryote fungi Candida.

Universal Vaccines Represent a Paradigm Shift

The employment of universal vaccines in the battle against infectious microbes represents a major paradigm shift that has the potential to revolutionize the field of vaccinology and improve the health of the human species. Targeting microbes that have defied easy vaccination solutions and decreasing the vaccination burden by elucidating universal antigenic components (Pathogen-Associated Molecular Patterns, PAMPS) will provide a 21st century solution to a problem present since the dawn of the human race.


Cassone A, Rappuoli R. Universal vaccines: shifting to one for many. mBio 2010; e00042-10. Accessed May 25, 2010.