The UNAIDS estimates that 38 million people currently live with human immunodeficiency virus (HIV) infection. Combination antiretroviral treatment has had great success in saving lives but is also associated with numerous medical and public health challenges. Vaccination remains the best and most cost-effective option for controlling HIV infection across the world. Professor Tomáš Hanke jointly from the University of Oxford, UK, and Kumamoto University, Japan, designs vaccines and coordinates clinical programs testing the most advanced vaccine candidates developed by his team in the UK, Europe, U.S. and Africa.
Ending AIDS with vaccination
Human immunodeficiency virus (HIV) type 1 represents 95% of all HIV infections worldwide and is responsible for the global HIV pandemic. If untreated, HIV-infected patients develop acquired immunodeficiency syndrome—better known as AIDS—that manifests as a progressive failure of their immune system. As a result, patients eventually succumb to opportunistic infections. Combination antiretroviral treatment (cART) has transformed the lives of people living with HIV, and dramatically decreased AIDS-related mortality and onward transmission of HIV. Unfortunately, the provision of cART to everybody who needs it faces many obstacles particularly in low- and middle-income countries. The cost, complexity of the treatment, necessity of regular monitoring of patients, threat of drug resistance, side effects, social stigma and the use of cART to prevent HIV infections (or pre-exposure prophylaxis), which further stretches the cART supply, make cART a suboptimal therapeutic and an unlikely stand-alone tool to end the HIV epidemic. Therefore, an effective vaccine for both prevention and cure of HIV is urgently needed.
Professor Tomáš Hanke and his team at the Jenner Institute at the University of Oxford, UK, together with their collaborators at the Joint Research Center for Human Retrovirus Infection, Kumamoto University, Japan, are studying T cell responses to HIV to inform vaccine development. In addition, Professor Hanke oversees Experimental Medicine trials of his leading T-cell vaccine candidates in healthy and HIV-positive people at several global sites and collaborates with prestigious universities and organizations such as the International AIDS Vaccine Initiative, IrsiCaixa AIDS Research Institute-HIVACAT in Spain, Imperial College London, the Kenya AIDS Vaccine Initiative-Institute for Clinical Research and National Institute of Allergy and Infectious Diseases. He also co-ordinates the "Globally Relevant AIDS Vaccine Europe-Africa Trials Partnership" consortium, acronymed GREAT, which builds research capacity and tests vaccine candidates in Eastern and Southern Africa, and is one of the principal investigators of the European AIDS Vaccine Initiative 2020.
Rational iterative development
Most of today's HIV vaccine research focuses on antibody-mediated immunity, which neutralizes cell-free viruses and typically involves exposing people to the outer HIV spike. However, to achieve HIV control, antibodies may need to be complemented by T-cell responses, the focus of Professor Hanke's research. There is no doubt that T cells contribute in an important way to anti-HIV immunity, whereby CD8 T cells known as "killer cells" directly kill virus-infected cells, the virus factories, and CD4 T cells or 'helper cells' assist and co-ordinate antibody and T-cell induction. "The trick is to induce not just any, but protective killer T cells that can slow or stop HIV," explains Professor Hanke. The first clinically tested vaccine that Professor Hanke and his colleagues developed was called HIVA. It was derived from an African clade A strain of HIV and was tested in over a dozen clinical trials. Following the field's full appreciation of the HIV's enormous ability to change, Professor Hanke improved his approach by focusing vaccine-elicited T cells on the functionally conserved regions of HIV, which are common to most HIV strains and essential for virus survival. If successful, such a vaccine could be deployed universally in all global regions. The prototype conserved immunogen was called HIVconsv (to emphasize conserved in addition to consensus sequences) and assembled highly conserved HIV regions into a chimeric protein alternating the global major HIV strains. This vaccine showed encouraging results in initial small clinical trials and informed the design of the second-generation conserved vaccines called HIVconsvX. Notable HIVconsvX improvements include the use of bioinformatics to redefine conserved regions and increase the vaccine match to the global HIV variants by using a so-called "mosaic" design. The HIVconsvX vaccines entered clinical evaluation in 2019 with further trials in the pipeline...
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