25 Sep 2019

An overview: HIV vaccine approaches at IGH

There are two major types of the human immunodeficiency virus or HIV, HIV-1 and HIV-2, and current treatment for HIV-1 is with life-long antiretroviral therapy. In this blog, IGH researchers Professor Bill Paxton and Dr Georgios Pollakis updates us on recent developments in HIV-1 vaccine approaches.

HIV-1 is the most common form of the HIV virus, and research to produce a vaccine is still ongoing. There is still considerable debate as to what is going to result in a successful HIV-1 vaccine, either preventative or therapeutic, and which strategies should be best employed to do so. It is still relatively unknown which combination of cellular or antibody immune responses are going to provide the optimal immunity required. The group of Bill Paxton and Georgios Pollakis are involved in two EU funded programmes analysing two different approaches, one is a T cell approach (a type of cell that forms the immune system) and the other is antibody (a protein produced by the immune system to neutralise pathogens).  

The ongoing H2020 funded European HIV-1 Vaccine Alliance programme includes HIV-1 infected individuals boosted with a substance designed to stimulate the immune system (an immunogen) aimed at heightening the response of T-cells to HIV-1. Participants receiving successful antiretroviral therapy will be vaccinated with a regime of a T-cell boosting immunogen after which they will be taken off therapy (treatment interruption) and time to viral rebound and to what extent measured. This will include a control arm to which time to viral rebound can be compared. During the vaccination protocol cellular immune responses will be measured by looking at HIV-1 viral loads. Furthermore, this study incorporates an arm receiving immunogen/placebo along with a special antibody (Vedolizumab) that has been linked with heightened immune response in the body’s mucosal linings. This study will identify whether therapeutic vaccination can provide benefit through increased elimination of HIV-1 infected cells and control of virus spreading through the blood. 

An EDCTP EU (bnAb-baby) funded proposal (started May 2019) is a vaccine proof of concept study looking to address whether neutralising antibodies have the potential to prevent HIV-1 infection in infants. A highly potent human neutralising antibody (VRC-007LS) will be administered to HIV-1 negative infants being breastfed by HIV-1 positive mothers. It is known that HIV-1 transmission can occur via this route even though mothers receive antiretroviral therapy. Breakthrough cases will be identified where virus being transmitted will be studied. These results will indicate whether high levels of circulatory antibodies have the potential to block HIV-1 transmission via this route of exposure and identify how potent they can be, whilst at the same time providing an indication of potential viral escape. How to induce such antibody responses would be the obvious aim stemming from these results.  

For vaccines to be successful they will likely have to induce immune responses that can clear HIV-1  ‘hiding’ in a resting or latent state in our own immune cells, or prevent the early establishment of such cells in newly infected individuals. Therefore, better understanding the cellular molecular environments that induce latency or support active viral replication is relevant to not only therapy but also vaccine success. Conversely, using therapeutic vaccines to activate T-cells may well enhance the possibility of HIV-1 transmission as well as virus replication in the case of therapeutic vaccines. Indeed, there are indications that the failure of the STEP vaccine trial, where more infections were reported among vaccine recipients than placebos, was due to cell activation and recruitment of cells to sites of exposure and thereby increased transmission. We are therefore actively involved in better understanding the molecular events that lead to increased infection and replication and are currently studying such mechanisms using cellular materials from the participants within our vaccine trials.


Certain types of parasite are known to change the immune response of their host through dampening or skewing T cell activation, to avoid the host immune system. Our most recent work (Mouser et.al. PLoS Pathogens e1007924, 5th Sep 2019) demonstrates that two different antigens (kappa-5 and omega-1) from parasitic blood flukes can differentially effect HIV-1 interactions with the immune system. Kappa-5 has been shown to bind dendritic cells (part of the immune system) and can prevent viral capture and transfer, whilst omega-1 matures dendritic cells towards skewing T cells with a reduced capacity to support HIV-1 replication. These results indicate that co-pathogen interactions can alter HIV-1 transmission as well as subsequent viral replication. Vaccines that induce a similar immune response would therefore be advantageous as they would reduce the detrimental effects mentioned earlier, such as increased virus replication and transmission.

9 Jul 2019

Meet the Researcher: Professor Alan Radford

Hannah Williams is a Year 10 Work experience student spending a week learning about the research and communication activity of IGH. Here, she interviews IGH’s Professor Alan Radford to find out about his work and why it’s important.

Alan Radford is Professor of Veterinary Health Informatics at the University Of Liverpool. His job entails teaching vet students about viruses of relevance to animals and public health, and researching the use of big data to improve the health of animals and their owners.

As part of his work he leads SAVSNET (Small Animal Veterinary Surveillance Network), a project which uses electronic health data and which monitors the many diseases or infecting organisms tested for at veterinary diagnostic laboratories across the UK. The latter data can be analysed alongside real-time data recorded at the end of consultations from participating veterinary surgeons to monitor, for example, what antibiotics are being prescribed and whether antibiotic resistance is present in bacteria causing infections in animals. Moreover, SAVSNET helps to make information accessible for all, which will increase awareness and knowledge of diseases in the small animal population in the UK.

So how does research on big data helps us understand health in animals? Animals are a big part of our lives, recent statistics show 49% of adults in the UK own a pet. We also eat animals, as well as keeping them as companions, therefore their welfare is very important to us.

How does this benefit society? Not only do we want our animals to be happy and healthy but the health of animals can impact our health too. For example, if your dog has an illness there is a chance it may be passed onto you. To ensure this doesn’t happen, big data is a new way to better understand diseases that could be passed to humans and reduce these diseases.

What impact will this research have? The data collected shows all types of ill health in animals, therefore by looking at disease, SAVSNET can identify new ways to reduce the risk of diseases. An example of their work is chocolate poisoning in dogs. We all know that chocolate is poisonous to dogs, however do you know what time of the year chocolate poisoning most often occurs? Through using big data, they found Christmas was in fact the most common time of the year for chocolate poisoning in dogs to occur. Using this information, owners can be reminded to be careful where they leave chocolate lying around at Christmas and it enables vets to be aware they may have more cases of chocolate poisoning in dogs during the Christmas period.

What changes do you hope to see? SAVSNET will help to understand individual diseases, how common they are in vet practice, which animals are most likely to be affected, what are the best treatments and best ways to avoid disease in the small animal population of the UK.

Currently, Professor Alan Radford is working on a variety of diseases, as well as antibiotic use, tumours, rabbit dental disease and fleas infestations. When asked what made him want to become a researcher he said he never planned to; he wanted to be a vet, however after he got his veterinary degree, he discovered he wanted to create new knowledge and understand animals at a population level where he could have broad impact on improving animal health.

Finally, some of his favourite things about his job include working with people, being stretched to think of new ways of doing things, with every day different and that he is starting to see the research he is doing have an impact.   



25 Jun 2019

Learning with the Experts - Liverpool Neuro ID Fellowship 2019


Learning with the Experts - Liverpool Neuro ID Fellowship 2019
Sofia Valdoleiros is a Portuguese medical resident in Infectious Diseases and from January until March 2019, caried out a clinical and academical internship in Neurology, with a primary focus in Neurological Infection, with the Liverpool Brain Infections Group (LBIG), under Professor Solomon, also with Dr. Benedict Michael and Dr. Christine Burness.
The academical module took place at the Institute of Infection and Global Health (IGH), where I was so well received and involved in the activities by everyone. Along with the academical work I developed, I got to participate in the Liverpool Brain Infections Group meetings, which included the discussion of major research projects, such as Enceph-UK, and UK-ChiMES, major programmes on adult and paediatric encephalitis. I even heard from Professor Solomon himself on “How to write a winning grant”! I was given the opportunity to attend international meetings of ground-breaking multicentre projects, such as Brain Infections Global and ZikaPLAN, and what an honour it was to be able to take part in these meetings and actually meet world leaders in Neurological Infectious Diseases research!
Exciting activities seem to be always happening, such as these meetings or Neuroscience Day or open discussions about neuroscience research. I was sad my internship ended before some other events took place, such as the Big Infection Day or the Neurological Infectious Diseases Course, but these sure were “replaced” by other activities, such as the e-learning Neuro ID Course or teaching sessions with Dr. Benedict Michael, who invested a lot of time in discussing fascinating Neuro ID cases with me. 
The clinical module took place at the Walton Centre and the Royal Liverpool University Hospital. As a renowned neurosciences medical centre, at the Walton Centre it is possible to attend experts’ subspecialty Neurology Clinics, observe inpatients with neuro-infection and attend stimulating meetings, from Grand Rounds to Lectures from Neurology experts and teaching sessions, and MDT meetings such as Spinal Infection, Infection Control or Neuroradiology. At the Royal, I accompanied Dr. Burness, a Neurology consultant with a special interest in Neurological Infection, in observing referrals from the ID wards, and attended the Neuro ID Clinic, an innovative approach bringing together a Neurology consultant (specialized in Neurological Infection – Professor Solomon, Dr. Michael and Dr. Burness) and an ID consultant (Dr. Defres) in a multidisciplinary view of the patient. I was also given the opportunity to attend the Encephalitis MDT monthly meeting at the National Hospital for Neurology and Neurosurgery in London. I am so grateful for the opportunity to learn from these Neuro ID experts’ experience and for their valuable insights. It will certainly change my approach of the neuro infected patient in Portugal.
Overall, the major point I highlight is the amount of opportunities (to learn, to participate in) I was given in only 3 months. With so much and so interesting and versatile things to do, these 3 months just completely flew by. Thank you so much to everyone!

25 Apr 2019

Measles: should vaccinations be compulsory?


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Measles virus. Design_Cells/Shutterstock
Tom Solomon, University of Liverpool

Following a measles outbreak in Rockland County in New York State, authorities there have declared a state of emergency, with unvaccinated children barred from public spaces, raising important questions about the responsibilities of the state and of individuals when it comes to public health.
Measles virus is spread by people coughing and spluttering on each other. The vaccine, which is highly effective, has been given with mumps and rubella vaccines since the 1970s as part of the MMR injection. The global incidence of measles fell markedly once the vaccine became widely available. But measles control was set back considerably by the work of Andrew Wakefield, which attempted to link the MMR vaccine to autism.

There is no such link, and Wakefield was later struck off by the General Medical Council for his fraudulent work. But damage was done and has proved hard to reverse.
In 2017, the global number of measles cases spiked alarmingly because of gaps in vaccination coverage in some areas, and there were more than 80,000 cases in Europe in 2018.

Anti-vaxxer threat

The World Health Organisation has declared the anti-vaccine movement one of the top ten global health threats for 2019, and the UK government is considering new legislation forcing social media companies to remove content with false information about vaccines. The recent move by the US authorities barring unvaccinated children from public spaces is a different legal approach. They admit it will be hard to police, but say the new law is an important sign that they are taking the outbreak seriously.

Most children suffering from measles simply feel miserable, with fever, swollen glands, running eyes and nose and an itchy rash. The unlucky ones develop breathing difficulty or brain swelling (encephalitis), and one to two per thousand will die from the disease. This was the fate of Roald Dahl’s seven-year-old daughter, Olivia, who died of measles encephalitis in the 1960s before a vaccine existed.

Roald Dahl’s daughter died of measles. Carl Van Vechten/Wikimedia Commons

When measles vaccine became available, Dahl was horrified that some parents did not inoculate their children, campaigning in the 1980s and appealing to them directly through an open letter. He recognised parents were worried about the very rare risk of side effects from the jab (about one in a million), but explained that children were more likely to choke to death on a bar of chocolate than from the measles vaccine.

Dahl railed against the British authorities for not doing more to get children vaccinated and delighted in the American approach at the time: vaccination was not obligatory, but by law you had to send your child to school and they would not be allowed in unless they had been vaccinated. Indeed, one of the other new measures introduced by the New York authorities this week is to once again ban unvaccinated children from schools.

Precedents

With measles rising across America and Europe, should governments go further and make vaccination compulsory? Most would argue that this is a terrible infringement of human rights, but there are precedents. For example, proof of vaccination against yellow fever virus is required for many travellers arriving from countries in Africa and Latin America because of fears of the spread of this terrifying disease. No-one seems to object to that.

Also, on the rare occasions, when parents refuse life-saving medicine for a sick child, perhaps for religious reasons, then the courts overrule these objections through child protection laws. But what about a law mandating that vaccines should be given to protect a child?

Vaccines are seen differently because the child is not actually ill and there are occasional serious side effects. Interestingly, in America, states have the authority to require children to be vaccinated, but they tend not to enforce these laws where there are religious or “philosophical” objections.
There are curious parallels with the introduction of compulsory seat belts in cars in much of the world. In rare circumstances, a seat belt might actually cause harm by rupturing the spleen or damaging the spine. But the benefits massively outweigh the risks and there are not many campaigners who refuse to buckle up.

I have some sympathy for those anxious about vaccinations. They are bombarded daily by contradictory arguments. Unfortunately, some evidence suggests that the more the authorities try to convince people of the benefits of vaccination, the more suspicious they may become.

I remember taking one of my daughters for the MMR injection aged 12 months. As I held her tight, and the needle approached, I couldn’t help but run through the numbers in my head again, needing to convince myself that I was doing the right thing. And there is something unnatural about inflicting pain on your child through the means of a sharp jab, even if you know it is for their benefit. But if there were any lingering doubts, I just had to think of the many patients with vaccine-preventable diseases who I have looked after as part of my overseas research programme.

Working in Vietnam in the 1990s, I cared not only for measles patients but also for children with diphtheria, tetanus and polio – diseases largely confined to the history books in Western medicine. I remember showing around the hospital an English couple newly arrived in Saigon with their young family. “We don’t believe in vaccination for our kids,” they told me. “We believe in a holistic approach. It is important to let them develop their own natural immunity.” By the end of the morning, terrified by what they had seen, they had booked their children into the local clinic for their innoculations.

In Asia, where we have been rolling out programmes to vaccinate against the mosquito-borne Japanese encephalitis virus, a lethal cause of brain swelling, families queue patiently for hours in the tropical sun to get their children inoculated. For them the attitudes of the Western anti-vaccinators are perplexing. It is only in the West, where we rarely see these diseases, that parents have the luxury of whimsical pontification on the extremely small risks of vaccination; faced with the horrors of the diseases they prevent, most people would soon change their minds.


Tom Solomon is the author of:

Roald Dahl’s Marvellous Medicine.The Conversation

Liverpool University Press provides funding as a content partner of The Conversation UK

Tom Solomon, Director of the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections, and Professor of Neurology, Institute of Infection and Global Health, University of Liverpool
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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