Towards better Influenza vaccines

Hello fellows

   First of all, Wish you a happy christmas. Its a good longtime since i put up something. I was too busy working on my personal projects and didn't get the time to write. Almost at the end of the year, i want to put a short post. And, probably, I will be taking a short break again. For now, 2 quick stories of interest.

Photo 1: Influenza vaccine
Source

   What has been the most sensational news in Medical Microbiology this year? I would say the first was Influenza study that finally came out with some positive decisions, the second was the XMRV story that finally has been nailed down. And the most recent one is again influenza.

    To make an influenza vaccine is a huge challenge. Every year, you have to determine what is the most important strain. Take the gene from relevant strain put it up in another strain (Which grows more easily in an egg) and then make a vaccine out of it. The whole process is a time consuming story. To overcome this problem is one of the big point in Influenza research. So 2 papers in Nature have made some significant contributions into this.

     The first paper is from SS Wong and RJ Webby (Link). The study showed that an mRNA encoding full-length influenza A/PuertoRico/8/1934 (PR8HA) hemagglutinin (HA) was in itself sufficiently immunogenic and induced anti-influenza B- and T-cell responses in mice. The authors simply put up the RNA into the test animal. The mRNA is probably taken up by Immune response cells, mRNA codes right away for the proteins and displayed in the surface, and you get an immune response. What is so smart about this? Well, all you need is a purified mRNA. Nothing else. The paper has looked into the possibility of RNA vaccine in contrast to DNA vaccines. A great in depth discussion on this was presented in TWiV 211 (Link)

    This synthetic vaccine was developed based on CureVac’s RNActive ® technology. CureVac’s CEO, commented, “The synthetic nature of our RNActive vaccines reduces production time dramatically and allows for sequence-matched vaccines that can be produced quickly and reliably in a scalable process. Additionally, our vaccines can be stored at room temperature, thereby avoiding the cold-chain in contrast to all other vaccines on the market and making worldwide distribution of our vaccines logistically and financially attractive.” For source go here.

Fig 1: M2 protein
Source

     The second paper is by Kim etal (Link). If the first problem of making a vaccine is the time the second more important problem is the variation. Every year and maybe more, the virus keeps changing its protein and universal vaccine is most desired. Out of the whole set of proteins in the Influenza A, is M2. If you can recall from my previous blogposts, I mentioned that M2 is a viroporin. Of interest, this protein has hardly changed in last 80 years, at least in strains of human pathology. The authors, engineered a tandem repeat of M2e epitope sequences (M2e5x) of human, swine, and avian origin influenza A viruses, which was expressed in a membrane-anchored form and incorporated in virus-like particles. The vaccine was effective. As i can say from their figures, the protection was impressive. All the vaccinated challenged mice survived. Thats impressive.

    My conclusion is very simple. We still have a long way to go for a better performance all round influenza vaccine. But these 2 papers, both in nature is opening some new doors and avenues.

Wong SS, & Webby RJ (2012). An mRNA vaccine for influenza. Nature biotechnology, 30 (12), 1202-4 PMID: 23222788

Kim MC, Song JM, O E, Kwon YM, Lee YJ, Compans RW, & Kang SM (2012). Virus-like Particles Containing Multiple M2 Extracellular Domains Confer Improved Cross-protection Against Various Subtypes of Influenza Virus. Molecular therapy : the journal of the American Society of Gene Therapy. PMID: 23247101