24 April marks the start of World Immunization Week – an annual campaign first launched in 2012. The week is one of 8 WHO international public health events, which include those targeting major infectious diseases – World AIDS day, World Tuberculosis (TB) day, World Malaria day, and World Hepatitis Day. These infections share a few features with each other which mean they all will continue to be global health threats for some time to come – this includes in particular the need for new or better vaccines. Where are we with vaccines for these very challenging diseases and indeed why are they so challenging?
AIDS is caused by HIV, a retroviral infection which crossed in to humans from chimpanzees in the last century and has spread to pandemic proportions. In humans, HIV targets the immune system ultimately leading to its collapse and the development of acquired immunodeficiency syndrome (AIDS). HIV has evolved complex strategies for long term infection and as a result is very hard to eliminate, either through immune responses or through drugs. The most modern drug treatments can lead to very effective suppression of the virus and thus protect the immune system. This approach – which requires the use of drug combinations – has saved countless lives and is the mainstay of therapy. Such drugs can also be used (along with other methods) to protect people against infection if they are at risk – so called Pre-exposure prophylaxis or PrEP. This situation is a remarkable turnaround from 30 years ago, when World AIDS day was launched. Things have not improved in this way in some of the other infections mentioned – drugs which were widely used to treat malaria and TB 3 decades ago are now plagued by widespread resistance in the micro-organisms.
However, effective as they are, HIV drugs cannot lead to a cure, as there is a long-term “reservoir” of virus in the body which is not eliminated by such an approach. Of the many millions infected, only one individual (the “Berlin patient”) has been cured of HIV – this was following complex medical therapy including a bone marrow transplant. There have been some individuals who have come close and there are a rare, but well recognised subset of “elite controllers” who show almost no signs of ongoing infection, largely as a result of very powerful immune responses. All these observations have spurred the field on to try and develop new cure strategies to eliminate the reservoir and allow people to stop taking antiviral therapy in the long term. Such approaches are still very much at the experimental stage and typically target the HIV reservoir using a combination of methods to reactivate the virus in the reservoir and then kill those cells through enhanced immune responses – potentially using novel “therapeutic” vaccines.
This situation contrasts markedly with that in hepatitis C – this is recognised with other hepatitis viruses affecting 500 million people globally on World Hepatitis Day in July each year. Hepatitis C Virus (HCV) causes, like HIV, long term infection, with potentially the development of liver failure and liver cancer. HCV was only discovered as an infectious agent in 1989 and like HIV is hard to eliminate as it has evolved an array of techniques to evade the host’s immune system. However, unlike HIV, it does not set up a “latent” or hidden reservoir. This means that antiviral drug treatments taken for a few weeks can lead to long-term cure. In the last 5 years, several such treatments (again drugs taken in combination) have been developed and are now available for different HCV strains. There are still many issues to solve, particularly identifying those at risk, and paying for the high costs of such treatments – but this three-decade arc, from discovery to effective cures has shown what can be done with concerted international effort.
World Immunization Week and the other internationally recognised public health days serve to remind of the everyday crises we face as a global population.
The issue of vaccine development unites HIV, HCV, TB, and malaria. Vaccination for a range of infections has saved countless lives globally and provides one of the key global health tools at our disposal. Although a vaccine exists for TB in the form of BCG, this is only really effective in infants and around 1 in 3 of the world’s population is infected. Malarial vaccines have been developed and approved but the long-term efficacy of these is still not proven. Even for hepatitis C, where the new drugs have transformed the outlook for patients, an effective vaccine would still have a major impact in interrupting spread and preventing new infections. One vaccine trial for HIV has shown marginal efficacy, while others, which looked impressive in pre-clinical trials, have been shown to be ineffective in the real-world setting.
The reason we lack a good vaccine for these infections is in some ways specific to each but there is an underlying commonality, which is that microbes have had a head start for thousands of years. Co-evolution between viruses or bacteria and their hosts have selected out micro-organisms which can exploit weaknesses in the immune system. One common trick, which is used by HIV, HCV, and malaria, is to keep modifying its shape, such that new immune responses must continuously chase a moving target. Generating a protective vaccine in each case will mean targeting the immune response to regions of the microbe which cannot be so readily mutated. These approaches are quite painstaking and the development (including the field testing) of new vaccines for these infections will be slow – but it is still an important task and even if the risk of failure for any one approach is still high, the gain for all of us is potentially huge.
World Immunization Week and the other internationally recognised public health days serve to remind of the everyday crises we face as a global population. They also serve to remind us that we need to fight these as a global population – the microbes themselves do not recognise international barriers. The stigma attached to many of these infections even today is also a problem which needs to be addressed – effective education, understanding, and acceptance of the issues surrounding the spread and prevention of such infections is the first step in controlling them. The development of new vaccines for all these major infections (and many others) is a priority which needs sustained public investment – but the human immune system can only do so much. It needs everybody’s commitment and, ultimately, everybody’s support.
Featured image credit: doctors office by annekarakash. Public domain via Pixabay.
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