A Universal, One-Shot Flu Vaccine?

ResearchBlogging.orgA Better Grip: T Cells Strengthen Our Hand against Influenza Clinical Infectious Diseases, 52 (1), 8-9 DOI: 10.1093/cid/ciq018Flu vaccines are important and useful, but also relatively ineffective compared to many other vaccines. Immunity is imperfect, there are many ‘strains’ of influenza in a given year only some of which are addressed by the available vaccine (though often the most common ones) and one year’s vaccine does not provide immunity to subsequent years’ influenza because the virus changes so much. Well, actually that’s not exactly true: The influenza virus has various different parts, and the parts that the traditional flu vaccine uses to induce an antigenic reaction in the potential hose is highly variable. Other parts of the flu virus are not as variable. If only a vaccine could be developed that uses the less variable part of the influenza virus, then perhaps it would be a universal, long-lasting vaccine that you take once, and become pretty much immune to all future influenza.

Well, it is possible that this has actually happened. A British research team has developed a vaccine that induces t-cells to respond to a conserved part of the influenza virus. It appears to be effective, and it appears to be safe. This is very preliminary …. much more work needs to be done to prove that it is safe, to suss out any rare side effects and, most importantly at this stage, to determine the ideal dosage.

Here’s what the researchers say:

…A vaccine providing protective immunity to the highly conserved internal antigens could provide longer-lasting protection against multiple influenza subtypes.

… We prepared a Modified Vaccinia virus Ankara (MVA) vector encoding nucleoprotein and matrix protein 1 (MVA−NP+M1) and conducted a phase I clinical trial in healthy adults.

… The vaccine was generally safe and well tolerated, with significantly fewer local side effects after intramuscular rather than intradermal administration. …

… We conclude that the vaccine was both safe and remarkably immunogenic, leading to frequencies of responding T cells that appear to be much higher than those induced by any other influenza vaccination approach. Further studies will be required to find the optimum dose and to assess whether the increased T-cell response to conserved influenza proteins results in protection from influenza disease.

Traditional vaccines teach the body’s immune system to create appropriate antibodies to fight a particular strain of flue. This new vaccine induces increased production of T-cells, using a different feature of the immune system. T-cells would destroy virus-infected cells.

The reported trial involved vaccinating eleven volunteers, then infecting them and eleven unvaccinated volunteers with the H2N2 flue. The vaccination appeared to work well. This is the first time this has been done in people, according to the study’s author:

This is the first time anyone’s tested if you can boost somebody’s T-cell response to flu and, having done that, if it helps protect against getting flu. It’s the first time anybody’s done that in people. Fewer of the people who were vaccinated got flu than the people who weren’t vaccinated. We did get an indication that the vaccine was protecting people, not only from the numbers of people who got flu but also from looking at their T-cells before we gave them flu. The people we vaccinated had T-cells that were more activated. The people we hadn’t vaccinated had T-cells as well but they were in a resting state so they would probably have taken longer to do anything. The volunteers we vaccinated had T-cells that were activated, primed and ready to kill. There were more T-cells in people we vaccinated and they were more activated.

Also, this approach to vaccination may work better on older individuals, for whom the traditional vaccine tends to be less effective.

The work needed to verify this result and bring it to the point of being an actual vaccine that we can have the use of, assuming the result holds up, will take time, probably years. But since the work was reported as an Open Access paper, you can read about it now (click the links below).

Berthoud, T., Hamill, M., Lillie, P., Hwenda, L., Collins, K., Ewer, K., Milicic, A., Poyntz, H., Lambe, T., Fletcher, H., Hill, A., & Gilbert, S. (2011). Potent CD8+ T-Cell Immunogenicity in Humans of a Novel Heterosubtypic Influenza A Vaccine, MVA-NP+M1 Clinical Infectious Diseases, 52 (1), 1-7 DOI: 10.1093/cid/ciq015

Hambleton, S. (2011). A Better Grip: T Cells Strengthen Our Hand against Influenza Clinical Infectious Diseases, 52 (1), 8-9 DOI: 10.1093/cid/ciq018

Comments

  1. #1 Mike Haubrich
    February 9, 2011

    You know what occurred to me on reading this post? Would the same ideas be able to be used to develop a vaccination to rhinovurus. Apparently, this has been nearly impossible because of a lack of cross-protections across serotypes (a phrase I just learne at at Google U.) But, if research can find a way to create a vaccine for the varieties of flu virus, then a vaccine for colds may not be such speculative fiction as to vex Dr, McCoy.

  2. #2 Greg Laden
    February 9, 2011

    Maybe. I think this approach (the T-cell part) actually comes from malarial vaccine research.

  3. #3 G.Shelley
    February 9, 2011

    The people we vaccinated had T-cells that were more activated. The people we hadn’t vaccinated had T-cells as well but they were in a resting state so they would probably have taken longer to do anything. The volunteers we vaccinated had T-cells that were activated, primed and ready to kill.

    I couldn’t tell from the interview, are these specific T-cells that are being primed, or is it a general T-cell activation?

  4. #4 Greg Laden
    February 9, 2011

    G. Shelley: Cytotoxic T cells (or CTL for cytotoxic T-lymphocytes) are primed by a specific antigen response caused by influenza (this is already in place, and the vaccine hypes it up) by which helper-cells (another form of T-cells) (CD4+ and CD8+ cells) mediate between virus-infected body cells and the CTL cells.

    In other words, there is already an anti-viral T-cell system in place, and it can deal with influenza. It just takes days to do so. This vaccine trains that system, so I suppose the answer to your question is that it is the former, but the the immune system is not really being adapted as much as with other forms of antibody production. (And, more exactly, it is probably CD4+/CD8+ system that is being primed.)

    I was hoping my friend Becca would jump in here because this is her area of expertise, IIRC.

  5. #5 Jason
    February 9, 2011

    “other parts of the flu vaccine are not as variable” should be “other parts of the flu virus are not…” no?

  6. #6 rob
    February 9, 2011

    wow. a better vaccine would be awesome. especially if the researchers could extend it to colds. i think i am developing a cold even as we speak. arrgh. bring me teh vaccines!

  7. #7 gwen
    February 9, 2011

    That would be friggin’ AWESOME! I get the flu vaccine every year as a part of my job (but I would do it anyway), and I have had H1N1 3 times in my life. I would love never to get it again! Next the scourge Malaria. It would be wonderful if they could create a vaccine against Malaria in the same way. Personally, I think they should concentrate on the vaccines people would appreciate. I can’t wait to read what the anti-vax moron machine will have to say about this, if it is every cleared for release!

  8. #8 Greg Laden
    February 9, 2011

    Jason, correct. Thanks. Fixed.

  9. #9 Jason
    February 9, 2011

    I can’t wait to read what the anti-vax moron machine will have to say about this, if it is every cleared for release!

    “That’s vaccinating against too many strains too soon!”

  10. #10 Leah DiPlacido
    February 9, 2011

    Actually testing vaccines in vivo (i.e., in humans or even in animals) is so important because testing how T cells respond in culture is often very different from how they behave in a living being. Generating effectiev T cell immunity is a big problem in developing cancer vaccines: there’s tons of antigens that seem to be very “immunogenic” in vitro, but do little to nothing in the host. Actually demonstrating protection from the microbe (or cancer) is, of course, the gold standard. Good to see that this seems to be working for a flu vaccine. . .

  11. #11 Skeptic Ginger
    February 11, 2011

    Seems to me I recall something about Tamiflu and Relenza working on a conserved part of the influenza virion.

    I recognize preventing replication provides fewer opportunities for resistance to emerge, but that influenza is one persistent bugger. Perhaps the champaign should wait for the after market experience.

  12. #12 Greg Laden
    February 11, 2011

    Ginger, the comparison isn’t really reasonable. Oseltamivir (Tamiflu, etc.) works in a totally different way. And, I’m sure you would agree, there is no reason to attribute special powers to the influenza virus just because it has … been difficult.

  13. #13 vaccine scheduler
    February 16, 2011

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  14. #14 plumbing
    April 15, 2011

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