James Merson, chief scientific officer at the Vaccines Research Unit at Pfizer, talks about the continuing challenge of finding a vaccine for HIV and MRSA.
Question - What is the greatest obstacle to finding an HIV vaccine? James Merson: HIV has been with us a little over 20 years now and enormous amounts of efforts have gone into trying to find a vaccine against HIV. The situation and our understanding is pretty straightforward, because the virus replicates very quickly, but also changes its genetic material (the genes that encode its proteins on a daily basis). The immune system has a problem targeting the virus such that on a daily basis the proteins encoded by the virus change. To generate what we call a neutralizing immune response takes weeks, so as far as the virus is concerned it’s a moving target. The immune system really does need a static target, a protein that doesn’t change such that because HIV mutates its genetic material so frequently, so rapidly the immune system is always several steps behind the virus. When the immune system does generate an immune response against a virus protein it kills that virus, but other viruses are selected and are able to replicate because there is no immune response feasible. So the challenges for HIV vaccines are very real and are very noticeable in the respect that we haven’t been able to find one over 20 years. However, as we continue to study the virus and the immune system we’re looking for regions of the virus that change less, simply because the function of that protein cannot be changed and, therefore, there are conserved regions within those proteins. Now the virus is clever in the respect that those conserved regions are often hidden from the immune system, but many investigators throughout the world are trying to exploit as be we can what some of those weak points in the viral replication cycle might be. So targeting conserved regions of these HIV proteins may be a way forward. I think our ability to generate better immune responses and faster so that antibodies which can neutralize the virus, what we call t-cells, white blood cells able to kill infected cells getting high enough levels of those types of cells to afford the killing of the infected cells, all very important. And even now people are looking at maybe not targeting necessarily HIV proteins, but proteins provided by the cells that the virus needs to replicate. If some of those proteins could be targeted safely by the immune system, we may prevent the virus from continuing its replication. So whereas perhaps a few years ago people were somewhat daunted by the continuing lack of success in finding an HIV vaccine typical human perseverance is probably still there. There are many people trying to find a vaccine and I’m hopeful that in at least my lifetime we will see a vaccine. It’s not beyond the realms of possibility. It just means we need to continue to better understand where the Achilles’ heels are on this virus. Topic – MRSA James Merson: So the MRSA bug or bacteria, the methicillin-resistant staphylococcus aureus organism is indeed changing, but it’s changing from the perspective of its ability to evade antibiotics, so it takes on multiple antibiotic resistances. However, the antibiotic resistant genes that enable this bacteria to avoid antibiotics- and it’s a very serious problem because we are running out of antibiotics with which to treat this disease. Hence the reason why we’d like to try and generate a vaccine to prevent people from becoming infected with MRSA. Now those genes that correlate with antibiotic resistance seem to have very little effect on the surface proteins of the bacterium, which are recognized by the immune system. So the challenge for us is to identify those proteins on the surface of the bacteria, which when the antibodies generated by the immune system bind to the bacterium can facilitate the removal and the killing of that bacteria from the human being. So the challenge right now, as I say, is to identify those proteins with which we can generate a vaccine to generate a protective immune response such that people don’t become infected with MRSA, such that they don’t need to be treated with antibiotics.