Author Archives: Imperial College

  1. The Quest for an HIV Vaccine

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    Since COVID-19 reared its head in December 2019, several effective vaccines have been developed against it. The Pfizer vaccine became the first to be approved just one year later, in December 2020.

    HIV has been around for decades and hundreds of thousands of people around the world die every year from the disease, and yet no effective vaccine exists.

    “We’ve been trying to develop a vaccine for HIV for over 30 years as a field,” says Professor Robin Shattock, lead researcher for the European AIDS Vaccine Initiative (EAVI2020). “It still remains one of the biggest biological challenges of a generation.”

    Why is HIV so hard to vaccinate against?

    Viruses are known to mutate – everyone will know that there have already been several variants of COVID-19 – but HIV operates on another scale, mutating incredibly quickly to produce new strains.

    Not only are there many, many strains of HIV, but the virus is also variable even within an infected individual.

    “If you look at the variability of viral strains of COVID-19, that’s probably less variability than you have within a single HIV-infected individual,” explains Professor Shattock. “So, the problem is orders of magnitude greater for HIV. There’s just so many strains, and the virus can change so quickly, that being able to have a vaccine that can keep up with that moving target is proving particularly challenging.”

    The continuously changing nature of HIV means that your body’s immune system finds it very difficult to produce antibodies that can fight off the virus, as it can rapidly change itself so that those antibodies are no longer effective.

    Individual parts of HIV that are targeted by antibodies are also not able to elicit a strong response from the immune system on their own, so a vaccine would have to target several aspects of HIV at once in order to prevent infection.

    The way that HIV works – by infecting T cells, your very own immune defences, and integrating its own genome into them to turn them into HIV factories – has also made the virus an expert at avoiding the immune system as it lasts in the body for a very long time.

    “COVID is a respiratory infection, and you eliminate it fairly quickly, in a matter of days or week or so, so it doesn’t have the time to adapt to the immune system,” says Professor Shattock. “For HIV, it’s a chronic disease, so somebody who is infected with HIV will carry the virus for the rest of their lifetime. And that means it’s got multiple opportunities to adapt and avoid the immune system. So it’s become really, really good at avoiding immune responses.”

    Rising to the challenge

    Despite the odds being stacked against them, EAVI2020 is rising to the challenge of developing a vaccine for HIV. And whilst the challenge is a daunting one, progress has been made.

    “We have had some success in terms of understanding that humans can make antibodies that are able to neutralise the huge variety of strains that are circulating around the world,” says Professor Shattock. “And what people are now trying to do is work out how you can make that happen with a vaccine in somebody who’s not been infected, so that those responses are there before somebody is exposed to the virus.”

    EAVI2020 currently has 8 clinical trials of vaccine candidates underway, and the team hopes to start to see some success with some of those. The team are also making the most of the latest vaccine technologies, such as mRNA vaccines that have been the basis for several of the COVID-19 vaccines. By harnessing this technology, they hope to be doing, instead of 8 trials over 5 years, 8 trials every year.

    EAVI2020 hopes that by bringing together HIV experts from around the world, they can bring forward the day where an HIV vaccine is a reality.

  2. World AIDS Vaccine Day 2022

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    “We’ve been trying to develop a vaccine for over 30 years as a field. It still remains one of the biggest biological challenges of the generation.” – Professor Robin Shattock.

    HIV remains a global health issue. According to UNAIDS,  there were 37.7 million [30.2 million–45.1 million] people living with HIV in 2020. 18 May marks World AIDS Vaccine Day, raising awareness of the need for an HIV vaccine to help bring about an HIV-free future, and celebrating the research that is happening around the world to make this a reality.

    Members of the EAVI2020 consortium came together to spread a message of support for the day:

     

    Professor Robin Shattock also spoke to Imperial College London’s podcast team to mark the day, discussing where we are at for a vaccine for HIV, what are some of the recent successes, and what hurdles remain. Listen to the full interview below.

  3. What’s next for an HIV vaccine?

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    As part of EAVI2020’s final Annual Meeting in Brussels, Professor Gabriella Scarlatti hosted a panel of EAVI2020 researchers and advisory group members in front of a live in-person and virtual audience to discuss an important question: What’s next for an HIV vaccine?

    Catch-up on the fascinating discussion below.

  4. EAVI quarterly newsletter | Special Edition – EAVI2020 PhD Training Program December 2021

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    Download the December Special Edition (.pdf)

    Foreword from Robin

    In this special issue we celebrate the success of our training programme in HIV vaccinology which has directly supported students in obtaining their PhD degrees. The programme has also supported career development of technicians and postdoctoral research from across the EU, both those directly funded by the EAVI2020 consortium and external researchers working on related HIV projects. An important component of building greater connectivity has been the successful exchanges of students between groups across the EU, Australia and the USA to learn new technologies.

    I am extraordinarily grateful to the leadership of Joan Joseph-Munne from Hospital Vall d’Hebron at Microbiology department / Vall d’Hebron Research Institute and Britta Wahren from the Karolinska Institutet, who led the program and provided mentorship to all our students. The programme provided new opportunities for early career researchers to learn basic and applied science in their field and obtain extended collaborations within both the consortium groups and associated scientific researchers at many universities in Europe, Australia and USA. This has helped accelerate their professional development, through tutorials, exchange visitor programmes and wet workshops activities.

    During their training, PhD students, technical staff and postdoctoral researchers have actively participated in and contributed to tutorials held at universities in Europe, and developed new skills through laboratory exchanges and visits to biotechnology companies. We are especially proud of all our students and celebrate both their commitment and achievements within the EAVI2020 programme, as well as their journey to new positions in both the academic and biotechnology sectors.

    Prof Robin Shattock
    EAVI2020 coordinator and on behalf of the EAVI2020 consortium

     

  5. EAVI2020 continues the fight | World AIDS Day 2021

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    For World AIDS Day 2021, the EAVI2020 clinicians and researchers are shedding a light on the EAVI2020 clinical trials that aim to help accelerate the search for an effective HIV vaccine. Every year on 1st December since 1988, World AIDS Day is an international day dedicated to raising awareness of the AIDS pandemic caused by the spread of the HIV virus. According to WHO, since the beginning of the pandemic, 36.3 million people have lost their lives and it was estimated that there were 37.7 million people living with HIV at the end of 2020, over two thirds of whom (25.4 million) are in the WHO African Region.

    It is a day to remember those who have perished due to AIDS and that international research projects such as EAVI2020, are continuing the fight to find an effective vaccine for the HIV virus that has so far evaded eradication for the past 30+ years. Learn more about EAVI2020’s clinical trials and what the dedicated consortium of researchers and clinicians aim to achieve.

    Click on each image to find out about EAVI2020’s clinical trials.

    info card on clinical trial HIV-CORE 0051

    HIV-CORE 0051

    info card on clinical trial HIV-CORE 0052

    HIV-CORE 0052

    info card on clinical trial EAVI2020 - 3SM

    EAVI2020-3SM

    info card on clinical trial EAVI2020_01

    EAVI2020-01

    info card on clinical trial BCN03

    BCN03

    Follow World AIDS Day campaigns on Twitter with #Rocktheribbon

    To donate and show your support, go to the National AIDS Trust website

  6. World AIDS DAY Part 1: EAVI2020’s research to a better future | Trial EAVI2020_3Sm

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    Hi! I’m the EAVI2020-3Sm trial and I am testing the VAC02 vaccine. VAC02 is an HIV vaccine candidate based on discovery of the immunogenicity of a conserved gp41 peptide, namely W614A-3S, recognized by natural broadly Neutralizing Ab detected in HIV-1 infected individuals. It is composed of gp41-3Sm peptide that is coupled to CRM197 in an adjuvant formulation. VAC02 is an HIV vaccine candidate based on discovery of the immunogenicity of a conserved gp41 peptide, namely W614A-3S, recognized by natural broadly neutralizing Ab detected in HIV-1 infected individuals. It is composed of gp41-3Sm peptide that is coupled to CRM197 in an adjuvant formulation. The first in man clinical trial will discern the safety and the immunogenicity of VAC02 as well as the induction of broadly neutralizing antibodies against HIV-1.

    Let me introduce you the team: Robin Shattock (Imperial College London, Study sponsor, UK), Behazine Combadiere, Vincent Vieillard and Patrice Debre (Institut National de Santé et de Recherche Medicale – Inserm, Cimi-Paris, France), Agence Nationale de Recherche sur le SIDA et Maladies Infectieuses Emergentes (ANRS-MIE, France) and Minka Therapeutics (France), they all work together to ensure I am successful!

    Progress has been made in epitope identification for the induction of broadly neutralizing antibodies. Peptide-based vaccination has become one of the challenges of this decade. Based on the discovery of natural broadly neutralizing antibodies against a conserved short epitope of GP41 in long-term non progressor HIV+ patients however rarely observed in HIV progressors, the EAVI2020-3Sm trial will be pioneering in the induction of such antibodies against HIV in man using VAC02 designed vaccine. Furthermore, the translation of VAC02 vaccine candidate into an experimental medicine (EM) study with results expected in 2022 will accelerate progress in the development of an HIV-1 vaccine.

    Find out more about the other EAVI2020 trials taking place:

    info card on clinical trial HIV-CORE 0051

    HIV-CORE 0051

    info card on clinical trial HIV-CORE 0052

    HIV-CORE 0052

    info card on clinical trial EAVI2020_01

    EAVI2020-01

    info card on clinical trial BCN03

    BCN03

    Follow World AIDS Day campaigns on Twitter with #Rocktheribbon

    To donate and show your support, go to the National AIDS Trust website

    For World AIDS Day 2022, the EAVI2020 clinicians and researchers are shedding a light on the EAVI2020 clinical trials that aim to help accelerate the search for an effective HIV vaccine. Every year on 1st December since 1988, World AIDS Day is an international day dedicated to raising awareness of the AIDS pandemic caused by the spread of the HIV virus. According to WHO, since the beginning of the pandemic, 36.3 million people have lost their lives and it was estimated that there were 37.7 million people living with HIV at the end of 2020, over two-thirds of whom (25.4 million) are in the WHO African Region.

    It is a day to remember those who have perished due to AIDS and that international research projects such as EAVI2020, are continuing the fight to find an effective vaccine for the HIV virus that has so far evaded eradication for the past 30+ years. Learn more about EAVI2020’s clinical trials and what the dedicated consortium of researchers and clinicians aim to achieve.

  7. World AIDS DAY Part 4: EAVI2020’s research to a better future | Trial HIV-CORE 0051

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    Hi! I am Trial HIV-CORE 0051. I am a phase 1/2a open-label trial to assess the safety and immunogenicity of candidate T-cell vaccines ChAdOx1.HTI and MVA.HTI given sequentially to healthy HIV-1/2 negative adult volunteers at the Jenner Institute, University of Oxford. Our trial aims to establish the initial safety and immunogenicity of the candidate on the path towards a preventive use of this strategy and is complemented by a series of HIV cure trials in early-treated PLWH.

    The HIV-CORE 0051 team including Dr Paola Cicconi (Principal Investigator) Prof Tomáš Hanke (Non-Clinical Principal Investigator), Dr Nicola Borthwick and Dr Edmund Wee (Immunology Laboratory Leads) and trial managers Dr Alison Crook and Ms Molly Glaze along with the many other team members that make up the HIV-CORE 0051 Trial team, in close collaboration with AELIX.

    The trial evaluates a candidate T-cell vaccine, which are being developed by a biotech company, AELIX Therapeutics. The regimen utilizes a prime with engineered replication-deficient simian (chimpanzee) adenovirus vector ChAdOx1 followed by a heterologous boost with a replication-deficient poxvirus vector called MVA. Both vectors deliver protein HTI (HIVACAT T-cell Immunogen) designed to generate protective HIV-1-specific T-cell targeting vulnerable sites of HIV-1. The HTI design was informed by human data, whereby the HTI-specific T cells were associated with better viral control in more than 1,000 people living with HIV-1 (PLWH) within a broad HLA class I and class II allele coverage. The immunogen was designed by the team led by Professor Christian Brander and Dr Beatriz Mothe at the Institut de Recerca de la Sida – IrsiCaixa in Barcelona.

    For the last decade, the HIV vaccine development has been almost entirely preoccupied with antibody-based protection, while the T-cell vaccines have been sadly ignored. It is only recently that highly rational T-cell strategies are being resurrected mainly in the context of HIV cure, where effective killer T cells will likely be key for drug-free HIV remission, perhaps even eradication. Current prevention focuses on behavioural and biomedical interventions and provision of antiretroviral drugs, however, an effective HIV-1 vaccine will help many people beyond the reach of today’s treatment and prevention options. Our trial which is aiming to understand the mechanisms and paths towards induction of protective T cells is therefore highly topical.

    Find out more about the other EAVI2020 trials taking place.

    info card on clinical trial HIV-CORE 0052

    HIV-CORE 0052

    info card on clinical trial EAVI2020 - 3SM

    EAVI2020-3SM

    info card on clinical trial EAVI2020_01

    EAVI2020-01

    info card on clinical trial BCN03

    BCN03

    Follow World AIDS Day campaigns on Twitter with #Rocktheribbon

    To donate and show your support, go to the National AIDS Trust website

    For World AIDS Day 2021, the EAVI2020 clinicians and researchers are shedding a light on the EAVI2020 clinical trials that aim to help accelerate the search for an effective HIV vaccine. Every year on 1st December since 1988, World AIDS Day is an international day dedicated to raising awareness of the AIDS pandemic caused by the spread of the HIV virus. According to WHO, since the beginning of the pandemic, 36.3 million people have lost their lives and it was estimated that there were 37.7 million people living with HIV at the end of 2020, over two-thirds of whom (25.4 million) are in the WHO African Region.

    It is a day to remember those who have perished due to AIDS and that international research projects such as EAVI2020, are continuing the fight to find an effective vaccine for the HIV virus that has so far evaded eradication for the past 30+ years. Learn more about EAVI2020’s clinical trials and what the dedicated consortium of researchers and clinicians aim to achieve.

  8. World AIDS DAY Part 5: EAVI2020’s research to a better future | Trial BCN03

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    Hi, I am EAVI2020 trial BCN03. Our trial takes place at IRSICAIXA with Christian Brander (Principal Investigator, IRSICAIXA) Beatriz Mothe (Principal Investigator, IRSICAIXA), working in collaboration with Rogier Sanders (Principal Investigator, AMC) and Dietmar Katinger (Principal Investigator, POLYMUN). Our trial focuses on a combined T- and B-cell, therapeutic HIV vaccine combining the HTI T cell vaccines with SOSIP envelope immunogens.

    Our trial is primarily focusing on the safety of the intervention and whether the intervention can induce sustained virus control once antiretroviral therapy (ART) is stopped. What sets our trial apart is that this is the first therapeutic vaccine trial that combines potent T and B cell immunogens in a combination regimen. We are hoping that this trial will test whether the addition of a B cell immunogen component to a T cell vaccine regimen can improve post-vaccination virus control compared to a single component regimen.

    Find out more about the other EAVI2020 trials taking place

    info card on clinical trial HIV-CORE 0051

    HIV-CORE 0051

    info card on clinical trial HIV-CORE 0052

    HIV-CORE 0052

    info card on clinical trial EAVI2020 - 3SM

    EAVI2020-3SM

    info card on clinical trial EAVI2020_01

    EAVI2020-01

    Follow World AIDS Day campaigns on Twitter with #Rocktheribbon

    To donate and show your support, go to the National AIDS Trust website

    For World AIDS Day 2021, the EAVI2020 clinicians and researchers are shedding a light on the EAVI2020 clinical trials that aim to help accelerate the search for an effective HIV vaccine. Every year on 1st December since 1988, World AIDS Day is an international day dedicated to raising awareness of the AIDS pandemic caused by the spread of the HIV virus. According to WHO, since the beginning of the pandemic, 36.3 million people have lost their lives and it was estimated that there were 37.7 million people living with HIV at the end of 2020, over two-thirds of whom (25.4 million) are in the WHO African Region.

    It is a day to remember those who have perished due to AIDS and that international research projects such as EAVI2020, are continuing the fight to find an effective vaccine for the HIV virus that has so far evaded eradication for the past 30+ years. Learn more about EAVI2020’s clinical trials and what the dedicated consortium of researchers and clinicians aim to achieve.

  9. World AIDS DAY Part 2: EAVI2020’s research to a better future | Trial HIV-CORE 0052

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    Hi! I am Trial HIV-CORE 0052; a phase I open-label trial aiming to establish and assess the safety and immunogenicity of candidate T-cell vaccines ChAdOx1.tHIVconsv1 and MVA.tHIVconsv3+MVA.tHIVconsv4 given in combination to healthy volunteers at low risk for HIV-1 infection at The Jenner Institute, University of Oxford London (Trial Sponsor) which will be followed by further studies towards both prevention of HIV infection and an HIV cure.

    The HIV-CORE 0052 team including Dr Paola Cicconi (Principal Investigator) Prof Tomáš Hanke (Non Clinical Principal Investigator), Dr Nicola Borthwick and Dr Edmund Wee (Immunology Laboratory Leads) and trial managers Dr Alison Crook and Ms Molly Glaze are aiming to test a candidate T-cell vaccine strategy against HIV-1. The tested regimen consists of a prime with engineered replication-deficient simian (chimpanzee) adenovirus vector ChAdOx1 followed by a heterologous boost with two replication-deficient poxviruses called MVA. These vectors deliver three unique mosaic algorithm-computed immunogens derived from the six most functionally conserved regions of the HIV proteome, collectively called HIVconsvX. Two regions are from the Gag including the whole capsid protein p24 and four are from the Pol proteins. These regions are common to most global HIV-1 variants and are hard to change and escape. These vaccines are so-called subunit genetic vaccines, are designated ChAdOx1.tHIVconsv1, MVA.tHIVconsv3 and MVA.tHIVconsv4 and aim to induce protective killer T-cell responses targeting HIV-1 ‘where it hurts’. If effective, they could work across all major HIV-1 clades and be deployed in all geographical regions.

    Throughout the challenging years of HIV vaccine development, when for the last decade most of the field has almost entirely focused on B-cell biology and antibody-based protection, Professor Hanke remained standing as one of a very few T-cell vaccinologists believing in vaccine-inducible protective cellular immunity, improving, and testing his highly rational T-cell strategy, which is now very much at the forefront of the current efforts.

    An HIV vaccine is urgently needed, however, simple vaccine solutions for this most difficult of viruses have remained extremely elusive. Development of an effective vaccine has been a slow and difficult process over four decades, but remarkable progress has been made in recent years. The experience with COVID-19 vaccines underscores how technologies under development for decades, such as RNA vaccines from 2001 and adenoviral vectors since 1991, can suddenly emerge as a leading and highly effective approach by building on decades of effort. Prof Hanke thinks it is likely that T cell-inducing vaccines for HIV-1 will reach this tipping point in the next 5 years and emerge as an additional tool to help control the HIV pandemic.

    Find out more about the other EAVI2020 trials taking place

    info card on clinical trial HIV-CORE 0051

    HIV-CORE 0051

    info card on clinical trial EAVI2020 - 3SM

    EAVI2020-3SM

    info card on clinical trial EAVI2020_01

    EAVI2020-01

    info card on clinical trial BCN03

    BCN03

    Follow World AIDS Day campaigns on Twitter with #Rocktheribbon

    To donate and show your support, go to the National AIDS Trust website

    For World AIDS Day 2021, the EAVI2020 clinicians and researchers are shedding a light on the EAVI2020 clinical trials that aim to help accelerate the search for an effective HIV vaccine. Every year on 1st December since 1988, World AIDS Day is an international day dedicated to raising awareness of the AIDS pandemic caused by the spread of the HIV virus. According to WHO, since the beginning of the pandemic, 36.3 million people have lost their lives and it was estimated that there were 37.7 million people living with HIV at the end of 2020, over two-thirds of whom (25.4 million) are in the WHO African Region.

    It is a day to remember those who have perished due to AIDS and that international research projects such as EAVI2020, are continuing the fight to find an effective vaccine for the HIV virus that has so far evaded eradication for the past 30+ years. Learn more about EAVI2020’s clinical trials and what the dedicated consortium of researchers and clinicians aim to achieve.

  10. World AIDS DAY Part 3: EAVI2020’s research to a better future | Trial EAVI2020_01

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    Hi! I am trial EAVI2020_01. Here at Imperial College London, both scientists and clinicians are leading my study which is modelling the interaction between rationally designed synthetic model viral protein immunogens (EAVI2020_01). We are studying immune responses to several different proteins that are modelled on HIV. The immunogens have a protein-adjuvant design and are given as an injection into the arm.

    Despite global efforts, HIV has proven one of the most difficult infections against which to develop a vaccine. We use sophisticated proteins that have been precisely developed to overcome these natural barriers. If the responses are promising, then we will have an early blueprint for making an HIV vaccine. Working on this trial are Professor Robin Shattock (Imperial College London, Scientific Lead), Dr Katrina Pollock (Imperial College London, Chief Investigator), and Dr Hannah Cheeseman (Imperial College London, Laboratory Lead).

    Vaccines are typically developed by focussing on the infection and not the immune response. The effectiveness of these vaccines is dependent on how most of us would usually respond to the infection if we were to come into contact with it. This strategy for making vaccines is restricting. For example, almost everyone who gets exposed to HIV will develop life threatening diseases without treatment.  The usual immune response is not protective.  The EAVI2020_01 study takes a different approach. Proteins that mimic the hidden parts of HIV are given several times to shepherd the body’s response precisely to make antibodies. The aim is that these antibodies will be broadly protective against all strains of HIV.

    The goal of HIV vaccine research is to make vaccines that induce broadly protective antibodies. This study will tell us how close we are to being able to do that. A successful outcome would pioneer the design of new vaccines for HIV and other highly challenging infectious diseases.

    Find out more about the other EAVI2020 trials taking place.

    info card on clinical trial HIV-CORE 0051

    HIV-CORE 0051

    info card on clinical trial HIV-CORE 0052

    HIV-CORE 0052

    info card on clinical trial EAVI2020 - 3SM

    EAVI2020-3SM

    info card on clinical trial BCN03

    BCN03

    Follow World AIDS Day campaigns on Twitter with #Rocktheribbon

    To donate and show your support, go to the National AIDS Trust website

    For World AIDS Day 2021, the EAVI2020 clinicians and researchers are shedding a light on the EAVI2020 clinical trials that aim to help accelerate the search for an effective HIV vaccine. Every year on 1st December since 1988, World AIDS Day is an international day dedicated to raising awareness of the AIDS pandemic caused by the spread of the HIV virus. According to WHO, since the beginning of the pandemic, 36.3 million people have lost their lives and it was estimated that there were 37.7 million people living with HIV at the end of 2020, over two-thirds of whom (25.4 million) are in the WHO African Region.

    It is a day to remember those who have perished due to AIDS and that international research projects such as EAVI2020, are continuing the fight to find an effective vaccine for the HIV virus that has so far evaded eradication for the past 30+ years. Learn more about EAVI2020’s clinical trials and what the dedicated consortium of researchers and clinicians aim to achieve.