̽��ֱ�� of Cambridge - Laboratory of Viral Zoonotics

New vaccine technology could protect from future viruses and variants

sc604 — Mon, 25 Sep 2023 15:10:32 +0000

̽��ֱ��vaccine antigen technology, developed by the ̽��ֱ�� of Cambridge and spin-out DIOSynVax in early 2020, provided protection against all known variants of SARS-CoV-2 – the virus that causes COVID-19 – as well as other major coronaviruses, including those that caused the first SARS epidemic in 2002.

̽��ֱ��studies in mice, rabbits and guinea pigs – an important step before beginning human clinical trials, currently underway in Southampton and Cambridge – found that the vaccine candidate provided a strong immune response against a range of coronaviruses by targeting the parts of the virus that are required for replication. ̽��ֱ��vaccine candidate is based on a single digitally designed and immune-optimised antigen.

Even though the vaccine was designed before the emergence of the Alpha, Beta, Gamma, Delta and Omicron variants of SARS-CoV-2, it provided a strong protection against all of these and against more recent variants, suggesting that vaccines based on DIOSynVax antigens may also protect against future SARS-CoV-2 variants.

DIOSynVax (Digitally Immune Optimised Synthetic Vaccines) uses a combination of computational biology, protein structure, immune optimisation, and synthetic biology to maximise and widen the spectrum of protection that vaccines can provide against global threats including existing and future virus outbreaks. Its vaccine candidates can be deployed in a variety of vaccine delivery and manufacturing platforms. ̽��ֱ��results are reported in the journal Nature Biomedical Engineering.

Since the SARS outbreak in 2002, coronavirus ‘spillovers’ from animals to humans have been a threat to public health, and require vaccines that provide broad-based protection. “In nature, there are lots of these viruses just waiting for an accident to happen,” said Professor Jonathan Heeney from Cambridge’s Department of Veterinary Medicine, who led the research. “We wanted to come up with a vaccine that wouldn’t only protect against SARS-CoV-2, but all its relatives.”

All currently available vaccines, such as the seasonal flu vaccine and existing Covid-19 vaccines, are based on virus strains or variants that arose at some point in the past. “However, viruses are mutating and changing all the time,” said Heeney. “Current vaccines are based on a specific isolate or variant that occurred in the past, it’s possible that a new variant will have arisen by the time we get to the point that the vaccine is manufactured, tested and can be used by people.”

Heeney’s team has been developing a new approach to coronavirus vaccines, by targeting their ‘Achilles heel’. Instead of targeting just the spike proteins on the virus that change to evade our immune system, the Cambridge vaccine targets the critical regions of the virus that it needs to complete its virus life cycle. ̽��ֱ��team identifies these regions through computer simulations and selecting conserved structurally engineered antigens. “This approach allows us to have a vaccine with a broad effect that viruses will have trouble getting around,” said Heeney.

Using this approach, the team identified a unique antigen structure that gave a broad-based immune responses against different Sarbeco coronaviruses, the large group of SARS and SARS-CoV-2 related viruses that occur in nature. ̽��ֱ��optimised antigen is compatible with all vaccine delivery systems: the team administered it as a DNA immunogen (in collaboration with the ̽��ֱ�� of Regensburg), a weakened version of a virus (Modified Vaccinia Ankara, supported by ProBiogen), and as an mRNA vaccine (in collaboration with Ethris). In all cases, the optimised antigen generated a strong immune response in mice, rabbits and guinea pigs against a range of coronaviruses. Based on a strong safety profile, the "first-in-human" clinical trials are ongoing at Southampton and Cambridge NIHR Clinical Research Facilities. ̽��ֱ��last booster immunisations will conclude by the end of September.

“Unlike current vaccines that use wild-type viruses or parts of viruses that have caused trouble in the past, this technology combines lessons learned from nature’s mistakes and aims to protect us from the future,” said Heeney. “These optimised synthetic antigens generate broad immune responses, targeted to the key sites of the virus that can’t change easily. It opens the door for vaccines against viruses that we don’t yet know about. This is an exceptionally different vaccine technology – it’s a real turning point.”

̽��ֱ��research was initially funded by the DHSC UK Vaccine Network programme and later in part by the Innovate UK DIOS-CoVax programme. ̽��ֱ��DIOSynVax pipeline includes vaccine candidates for influenza viruses, haemorrhagic fever viruses, and coronaviruses including SARS-CoV-2, the latter of which is currently in clinical trials.

DIOSynVax is a spin-out company from the ̽��ֱ�� of Cambridge, established in 2017 with the support of Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm. Jonathan Heeney is the Professor of Comparative Pathology at the ̽��ֱ�� of Cambridge, and a Fellow at Darwin College.

Reference:
Sneha Vishwanath et al. ‘A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses.’ Nature Biomedical Engineering (2023). DOI: 10.1038/s41551-023-01094-2

Studies of a ‘future-proof’ vaccine candidate have shown that just one antigen can be modified to provide a broadly protective immune response in animals. ̽��ֱ��studies suggest that a single vaccine with combinations of these antigens – a substance that causes the immune system to produce antibodies against it – could protect against an even greater range of current and future coronaviruses.

This is an exceptionally different vaccine technology – it’s a real turning point

Jonathan Heeney

Uma Shankar sharma via Getty Images

Virus mutation

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Cambridge ̽��ֱ��’s needle-free coronavirus vaccine begins clinical trials in home city

cjb250 — Mon, 24 Apr 2023 07:00:20 +0000

̽��ֱ��vaccine – known as DIOS-CoVax – has been developed by Professor Jonathan Heeney at the ̽��ֱ�� of Cambridge and spin-out company DIOSynVax. It is envisaged as a booster targeting SARS-CoV-2 and relatives that threaten future coronavirus pandemics.

This next generation vaccine is administered through a needle-free ‘injection’ – a blast of air that delivers it into the skin. It has already been part of safety trials conducted at the NIHR Southampton Clinical Research Facility, but now recruitment is being expanded to Cambridge.

Professor Heeney said: “We’re excited to be bringing our vaccine ‘home’ and are looking to recruit healthy volunteers to help in this crucial stage of development towards what we hope will eventually become a universal coronavirus vaccine.

“Our vaccine is innovative, both in terms of how it aims to protect against thevirus responsible for our current pandemic and future coronaviruses, but also in how it is delivered. If you’re someone who hates needles, our vaccine could be the answer as it’s delivered by a jet of air, not a needle.”

If the clinical trials are successful, the vaccine could be scaled up and manufactured as a powder to boost global vaccination efforts, particularly in low- and middle-income countries.

̽��ֱ��clinical trials team at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust is looking for healthy volunteers aged 18-50 to take part in the study. Volunteers will receive payment for their time, and participation on the trial will last around 12 months with volunteers attending 11 visits. To find out more, contact the Project Management Team at cuh.dioscovaxtrial@nhs.net.

Funding for the development of the vaccine has come from Innovate UK, part of UK Research and Innovation.

DIOSynVax is a spin-out company from the ̽��ֱ�� of Cambridge, established in 2017 with the support of Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm. Professor Heeney is a Fellow at Darwin College, Cambridge.

Trials of a novel needle-free coronavirus vaccine begin in Cambridge

Lloyd Mann ( ̽��ֱ�� of Cambridge)

Vaccine being administered by needle-free injection into a volunteer's arm

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Cambridge vaccine expert in $42million partnership to develop 'future-proofed' coronavirus vaccines

cjb250 — Tue, 08 Mar 2022 10:00:33 +0000

̽��ֱ��investment from the Coalition for Epidemic Preparedness Innovations (CEPI) will support the development of an mRNA vaccine. DIOSynVax, led by Professor Jonathan Heeney, Head of the Laboratory of Viral Zoonotics, ̽��ֱ�� of Cambridge, will design and select the lead antigen through proof-of-concept preclinical studies, and undertake initial clinical development through Phase I/II studies.

DIOSynVax uses the combination of protein structure, computational biology and immune-optimisation to maximise the protection that vaccines can provide against global threats including existing and future virus outbreaks. Its vaccine candidates can be deployed in a variety of vaccine delivery and manufacturing platforms.

̽��ֱ��DIOSynVax pipeline includes vaccine candidates for haemorrhagic fever viruses, influenza, and SARS-CoV-2, the latter of which is currently in clinical trials.

If DIOSynVax’s novel antigen design is successfully deployed using the intended mRNA platform, it could potentially be used to enable rapid development of vaccines against so-called Disease X – unknown pathogens with pandemic potential that have yet to emerge.

Professor Jonathan Heeney, Cambridge, said: "We are excited to be working with CEPI on its ground-breaking mission to leverage revolutionary science and technology to outmanoeuvre and minimise future pandemic threats.

"Our approach is to be ahead of the next pandemic - to deliver custom designed, immune selected vaccine antigens – which is ideal to prevent diseases caused by complex viruses such as the large and diverse family of coronaviruses. If successful, it will result in a safe, affordable NextGen vaccine for widespread use.”

CEPI, DIOSynVax and the ̽��ֱ�� of Cambridge are committed to enabling global equitable access to the vaccines developed through this partnership. Under the terms of the funding agreement, DIOSynVax has committed to achieving equitable access to the outputs of this project.

Dr Richard Hatchett, CEO of CEPI, said: “ ̽��ֱ��UK Government and the country’s world-leading scientific institutions have been pivotal to the global response to COVID-19. From the development of the CEPI-supported Oxford/AstraZeneca vaccine – which is used in more countries than any other – to the ground-breaking Recovery trial to evaluate life-saving treatments like dexamethasone, British science has played a leading role in protecting the world from COVID-19.

“I am excited to further strengthen CEPI’s strong ties to British science through this partnership with DIOSynVax, Cambridge, to develop a vaccine with the potential to protect against variants of SARS-CoV-2 and other Betacoronaviruses in the future. Coronaviruses have now proven their pandemic potential, so it’s imperative for global health security that we invest in R&D now to future-proof the world against the threat of coronaviruses.”

̽��ֱ��announcement was made today at the Global Pandemic Preparedness Summit, which brings together a unique mix of leaders across governments, international agencies, science and academia, industry, philanthropy, and civil society to explore how to collectively prepare for future viral threats and mobilise critical resources and political support for CEPI’s work.

DIOSynVax is a spin-out company from the ̽��ֱ�� of Cambridge, set up in 2017 with the support of Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm.

Professor Heeney is a Fellow at Darwin College, Cambridge.

Adapted from a press release from CEPI

Prime Minister Boris Johnson announced that DIOSynVax, a biotech spinout of the ̽��ֱ�� of Cambridge, will receive $42 million (about £32 million) to develop a vaccine candidate that could provide protection against both existing and future variants of SARS-CoV-2 – the virus that causes COVID-19 – as well as other major coronaviruses, including those that cause SARS and MERS.

Our approach is to be ahead of the next pandemic - to deliver custom designed, immune selected vaccine antigens – which is ideal to prevent diseases caused by complex viruses such as the large and diverse family of coronaviruses

Jonathan Heeney

Nick Saffell ( ̽��ֱ�� of Cambridge)

Professor Jonathan Heeney

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Cambridge COVID vaccine in clinical trials

cjb250 — Tue, 14 Dec 2021 08:15:52 +0000

Safety trials are underway for a vaccine developed by Cambridge researchers that could be used as a booster targeting COVID-19 virus variants and relatives that threaten future coronavirus pandemics.

Cambridge-developed SARS-CoV-2 vaccine receives £1.9million from UK government for clinical trial

cjb250 — Tue, 25 Aug 2020 23:01:09 +0000

Innovate UK, the UK government’s innovation agency, has provided the funding for a collaboration between Cambridge spin-out company DIOSynVax (which is contributing an additional £400,000 to the trial), the ̽��ֱ�� of Cambridge and the ̽��ֱ�� Hospital Southampton NHS Foundation Trust.

SARS-CoV-2 is a coronavirus, a class of virus named after their appearance: spherical objects, on the surface of which sit ‘spike’ proteins. ̽��ֱ��virus uses these spikes to attach to and invade cells in our body. One vaccine strategy is to block this attachment; however, not all immune responses against this virus and against this spike protein are protective – antibodies to the wrong part of the spike protein have been implicated in triggering hyper-inflammatory immune responses causing life-threatening COVID-19 disease. Added to this, SARS-CoV-2 is mutating and changes in the virus spike protein during the COVID-19 pandemic have already been observed to be widespread.

To develop their new vaccine candidate – DIOS-CoVax2 – the team use banks of genetic sequences of all known coronaviruses, including those from bats, the natural hosts of many relatives of human coronaviruses. ̽��ֱ��team have developed libraries of computer-generated antigen structures encoded by synthetic genes that can train the human immune system to target key regions of the virus and to produce beneficial anti-viral responses. These immune responses include neutralising antibodies, which block virus infection, and T-cells, which remove virus-infected cells. This ‘laser-specific’ computer generated approach is able to help avoid the adverse hyper-inflammatory immune responses that can be triggered by recognition of the wrong parts on the coronavirus’s surface.

Professor Jonathan Heeney, head of the Laboratory of Viral Zoonotics at the ̽��ֱ�� of Cambridge, and founder of DIOSynVax, said: “Our approach involves 3D computer modelling of the SARS-CoV-2 virus’s structure. It uses information on the virus itself as well as its relatives – SARS, MERS and other coronaviruses carried by animals that threaten to ‘spill-over’ to humans again to cause future human epidemics.

“We’re looking for cracks in its armour, crucial pieces of the virus that we can use to construct the vaccine to direct the immune response in the right direction. Ultimately we aim to make a vaccine that will not only protect from SARS-CoV-2, but also other related coronaviruses that may spill over from animals to humans.

“Our strategy includes targeting those domains of the virus’s structure that are absolutely critical for docking with a cell, while avoiding the parts that could make things worse. What we end up with is a mimic, a synthetic part of the virus minus those non-essential elements that could trigger a bad immune response.”

While most vaccines use RNA or adenoviruses to deliver their antigens, DIOSynVax’s is based around DNA. These synthetic gene inserts are very versatile and can also be placed within a number of different vaccine delivery systems that other companies are using. Once an antigen is identified, the key piece of genetic code that the virus uses to produce the essential parts of its structure is inserted into a DNA parcel known as a vector. ̽��ֱ��body’s immune cells take up the vector, decode the DIOS-vaccine antigen and use the information to program the rest of the immune system to produce antibodies against it.

This DNA vector has already been shown to be safe and to be effective at stimulating an immune response against other pathogens in multiple phase I and early phase II trials.

̽��ֱ��proposed vaccine can be freeze-dried as a powder and is therefore heat stable, meaning that it does not need to be cold-stored. This makes transport and storage much more straightforward – which is particularly important in low- and middle-income countries where the infrastructure to make this possible can be costly. ̽��ֱ��vaccine can be delivered pain-free without a needle into the skin, using the PharmaJet Tropis ® intradermal Needle-free Injection System, which delivers the vaccine in less than a 1/10th of a second by spring-powered jet injection.

Dr Rebecca Kinsley, Chief Operating Officer of DIOSynVax and a postdoctoral researcher at the ̽��ֱ�� of Cambridge, added: “Most research groups have used established approaches to vaccine development because of the urgent need to tackle the pandemic. We all hope the current clinical trials have a positive outcome, but even successful vaccines are likely to have their limitations – they may be unsuitable for vulnerable people, and we do not know how long their effects will last for, for example.

“Our approach – using synthetic DNA to deliver custom designed, immune selected vaccine antigens – is revolutionary and is ideal for complex viruses such as coronavirus. If successful, it will result in a vaccine that should be safe for widespread use and that can be manufactured and distributed at low cost.”

̽��ֱ��UKRI funding will allow the team to take the vaccine candidate to clinical trial, which will take place at the National Institute for Health Research (NIHR) Southampton Clinical Research Facility at the ̽��ֱ�� Hospital Southampton NHS Foundation Trust and could begin as early as late autumn this year.

Professor Saul Faust, Director of the NIHR Southampton Clinical Research Facility, said: “It is critical that different vaccine technologies are tested as part of the UK and global response to the pandemic as at this stage no one can be sure which type of vaccine will produce the best and most long-lived immune responses.

“It is especially exciting that the clinical trial will test giving the vaccine through people’s skin using a device without any needles as together with stable DNA vaccine technology this could be a major breakthrough in being able to give a future vaccine to huge numbers of people across the world.”

Phil Packer, Innovation Lead for AMR and Vaccines at Innovate UK, said: “Innovate UK is excited to fund the development of DIOS-CoVax and its assessment in Phase I Clinical Trials. ̽��ֱ��rapid identification of the DIOS-CoVax2 vaccine was made possible because DIOSynVax were able to rapidly utilise its vaccine platform technology previously developed for an Ebola/ Marburg/Lassa fever vaccine.

“That was delivered by Innovate UK as part of DHSC’s Global Health Security Programme, which saw £110m invested in a new UK Vaccine Network charged with developing new vaccines and technologies to tackle diseases with epidemic potential.”

DIOSynVax is a spin-out company from the ̽��ֱ�� of Cambridge, set up in 2017 with the support of Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm.

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A Cambridge-developed vaccine candidate against SARS-CoV-2 could begin clinical trials in the UK in late autumn or early next year, thanks to a £1.9million award from the UK government.

Our approach – using synthetic DNA to deliver custom designed, immune selected vaccine antigens – is revolutionary and is ideal for complex viruses such as coronavirus. If successful, it will result in a vaccine that should be safe for widespread use and that can be manufactured and distributed at low cost

Rebecca Kinsley

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Coronavirus

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Cambridge research team working towards vaccine against COVID-19

cjb250 — Tue, 17 Mar 2020 11:42:35 +0000

It is hard now to conceive that two months ago, few people had heard of the new coronavirus. Now, the virus, which causes the disease COVID-19, has spread to every corner of the globe. ̽��ֱ��World Health Organization has officially declared the outbreak a pandemic.

With the threat of hundreds of thousands – possibly millions – of people being infected and healthcare systems becoming overwhelmed, the race is on to develop a vaccine that will protect individuals and slow the spread of the disease. But Professor Jonathan Heeney, Head of the Laboratory of Viral Zoonotics at the ̽��ֱ�� of Cambridge, and one of the people working on a vaccine, says that coronaviruses present a particular challenge to vaccine developers.

Coronaviruses are named after their appearance: they are spherical objects, on the surface of which sit ‘spike’ proteins. ̽��ֱ��virus uses these spikes to attach to and invade cells in our body. Once inside, the virus uses the cell’s own machinery to help itself replicate and spread throughout the body, causing disease and allowing it to transmit onwards.

Traditionally, scientists would develop vaccines that programme the body to produce antibodies that recognise and block these spikes. But this strategy can misfire with coronaviruses due to a phenomenon known as ‘antibody-induced enhancement’ or ‘vaccine-induced enhancement’, says Heeney.

“If you make antibodies against the spike, they can end up binding to it and helping the virus invade important immune cells known as monocyte-macrophages. Rather than destroying the virus, these cells can then end up being reprogrammed by the viruses, exacerbating the immune response and making the disease much, much worse than it would otherwise be.”

This phenomenon is well known, says Heeney, but it could still slow down development of a vaccine. “Researchers will want to be confident that their vaccine candidates are safe – that they don’t inadvertently make the disease worse – before they are tested in humans.”

As well as his Professorship at the Department of Veterinary Medicine, Heeney is CEO of DIOSynVax, a spin-out company set up in 2017 with the support of Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm. Its strapline is ‘We change the way vaccines are made’. In the past few years, Heeney has won significant funding from the Bill & Melinda Gates Foundation and Innovate UK to develop new vaccines for diseases ranging from influenza to Ebola and other haemorrhagic fevers. It is this technology that he is now applying to the coronavirus.

DIOSynVax’s approach involves using computer modelling of the virus’s structure, created using information on the COVID-19 virus itself as well as its relatives – SARS, MERS and other coronaviruses – and identifying cracks in its armour, crucial pieces of the spikes that will form part of the vaccine, to disable the virus but without making the infection worse.

“A vaccine strategy needs to be laser specific, targeting those domains of the virus’s structure that are absolutely critical for docking with a cell, while avoiding the parts that could make things worse,” he says. “Our technology does just that.”

Their approach is to look at the genetics of these viruses to identify the key piece of genetic code that the virus uses to produce the essential part of its coat, the spikes, that are important for docking with a cell and to target these elements with the vaccine.

“What we end up with is a mimic, a mirror image of part of the virus, but minus its bad parts, the non-essential parts that could trigger those bad immune responses. What remains is just the magic bullet, essentially, to trigger the right type of immune response.”

Then, using a combination of artificial intelligence and synthetic biology, the team create a vaccine that includes this piece of genetic code, which can be injected into an individual. ̽��ֱ��body’s immune cells will then find it, decode it and us the information to program the rest of the immune system to produce antibodies against it.

̽��ֱ��next step is to then test the vaccine in pre-clinical trials – in other words, give the vaccine to mice to check that it is safe to use. Mice are an important part of vaccine research: their physiology and immune systems are similar enough to ours to enable researchers to minimise the risk to humans taking part in clinical trials.

DIOSynVax’s approach is much faster than current vaccine development technologies, says Heeney, which means that even allowing for essential pre-clinical mouse studies, his vaccine candidate could be ready for human clinical trials as early as June. He is currently seeking funding to pursue his work further and a pharmaceutical company with whom to partner on clinical trials.

“We need a ‘big pharma’ partner to help us scale up our activities,” he says. “Our vaccine designs are made so that they can be easily integrated into any proprietary vaccine platform that a pharmaceutical company may have ready.”

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Updates for staff and students at the ̽��ֱ�� and Colleges on coronavirus (COVID-19)

Read the latest advice for staff and students at the ̽��ֱ�� and Colleges

̽��ֱ��race is on to find a vaccine against the new COVID-19 coronavirus. Professor Jonathan Heeney explains why a cautious approach is needed and how his team is using new technology developed for influenza and Ebola viruses to target the new infection.

A vaccine strategy needs to be laser specific, targeting those domains of the virus’s structure that are absolutely critical for docking with a cell, while avoiding the parts that could make things worse

Jonathan Heeney

COVID-19 coronavirus vaccine: everything you need to know

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Study clears important hurdle towards developing an HIV vaccine

cjb250 — Wed, 13 Sep 2017 07:03:22 +0000

In a study published in 2009, results from a clinical trial carried out in Thailand found that an experimental vaccine against HIV lowered the rate of human infection by 31%. This gave cautious optimism that a vaccine against the virus might be a feasible prospect. A vaccine has obvious advantages over treatment with anti-retroviral drugs in that prevention could lead to eradication.

However, one of the major problems that prevented the vaccine from generating long-lasting protection was that the key immune response it needed to generate was very short-lived. ̽��ֱ��reason has now become clear and researchers have found a potential solution.

When a virus enters the body, its aim is to get into our cells and replicate itself again and again, spreading throughout the body. HIV is especially notorious because a protein on its outer coat specifically targets CD4 T-helper cells, the master regulators of the immune system. These cells produce important signals for other types of immune cell: B-cells, which make antibodies; and T-killer cells, which kill virus-infected cells.

By specifically targeting the CD4 T-helper cells, HIV cripples the command and control centre of the immune system and prevents immune defences from working effectively. HIV does not even need to enter and kill the CD4 T-cells – it can cause a functional paralysis of these cells simply by binding its gp140 with the CD4 receptor, an important molecule on the surface of T-helper cells.

HIV’s envelope proteins are a key component of vaccines to protect against HIV infection. ̽��ֱ��body’s immune system targets this protein and generates antibodies directed at HIV’s outer coat to prevent the virus from entering the cells. If the effects of the vaccine last long enough, then with the assistance of robust helper T-cells, the human body should be able to develop antibodies that neutralise a large variety of HIV strains and protect people from infection.

Previous studies showed that vaccinating using a form of the outer coat protein called gp140 leads to the triggering of B-cells which produce antibodies to the virus, but only for a brief period and insufficient to generate sufficient antibodies that are protective from HIV infection over a long period.

Working with scientists in the UK, France, the USA, and the Netherlands, Professor Jonathan Heeney from the Laboratory of Viral Zoonotics at the ̽��ֱ�� of Cambridge recognised that the binding of gp140 to the CD4 receptor on T-helper cells was probably causing this block, and that by preventing gp140 attaching to the CD4 receptor, the short-term block in antibody producing B-cells could be overcome.

In two back-to-back studies published in the print edition of Journal of Virology, the research team has demonstrated for the first time that this approach works, providing the desired responses that were capable of lasting over a year.

“For a vaccine to work, its effects need to be long lasting,” says Professor Heeney. “It isn’t practical to require people to come back every 6-12 months to be vaccinated. We wanted to develop a vaccine to overcome this block and generate these long-lived antibody producing cells. We have now found a way to do this.”

̽��ֱ��study showed that the addition of a tiny specific protein patch to the gp140 protein dramatically improved B-cell responses by blocking binding to the CD4 receptor and hence preventing the paralysis of T-helper cells early in the key stages of the immune response – like preventing a key from getting stuck in a lock. This small patch was one of several strategies to improve gp140 for an HIV vaccine by a team led by Susan Barnett (now at the Bill and Melinda Gates Foundation).

This modified vaccine approach now better stimulates long-lasting B-cell responses, boosting the ability of B-cells to recognise different contours of the virus coat and to make better antibodies against it. This new finding will allow HIV vaccines to be developed that give the immune system enough time to develop the essential B-cell responses to make protective antibodies.

“B-cells need time to make highly effective neutralising antibodies, but in previous studies B-cell responses were so short lived they disappeared before they have the time to make all the changes necessary to create the ‘silver bullets’ to stop HIV,” adds Professor Heeney.

“What we have found is a way to greatly improve B-cell responses to an HIV vaccine. We hope our discovery will unlock the paralysis in the field of HIV vaccine research and enable us to move forward.”

̽��ֱ��team now hopes to secure funding to test their vaccine candidate in humans in the near future.

̽��ֱ��studies were funded by the National Institutes of Health, USA, and the Isaac Newton Trust Cambridge.

Reference

Bogers, WMJM, et al. Increased, Durable B-Cell and ADCC Responses Associated with T-Helper Cell Responses to HIV-1 Envelope in Macaques Vaccinated with gp140 Occluded at the CD4 Receptor Binding Site. Journal of Virology; DOI: 10.1128/JVI.00811-17.

Shen, X et al. Cross-Linking of a CD4-Mimetic Miniprotein with HIV-1 Env gp140 Alters Kinetics and Specificities of Antibody Responses against HIV-1 Env in Macaques. Journal of Virology; DOI: 10.1128/JVI.00401-17.

An international team of researchers has demonstrated a way of overcoming one of the major stumbling blocks that has prevented the development of a vaccine against HIV: the ability to generate immune cells that stay in circulation long enough to respond to and stop virus infection.

For a vaccine to work, its effects need to be long lasting. It isn’t practical to require people to come back every 6-12 months to be vaccinated

Jonathan Heeney

NIAID

3D print of HIV (edited)

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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̽��ֱ�� of Cambridge - Laboratory of Viral Zoonotics

New vaccine technology could protect from future viruses and variants

Cambridge ̽��ֱ��’s needle-free coronavirus vaccine begins clinical trials in home city

Read more at: Cambridge coronavirus vaccine enters clinical trial

Trials of a novel needle-free coronavirus vaccine begin in Cambridge

Cambridge vaccine expert in $42million partnership to develop 'future-proofed' coronavirus vaccines

Cambridge COVID vaccine in clinical trials

Cambridge-developed SARS-CoV-2 vaccine receives £1.9million from UK government for clinical trial

How you can support Cambridge's COVID-19 research effort

Cambridge research team working towards vaccine against COVID-19

How you can support Cambridge's COVID-19 research effort

Updates for staff and students at the ̽��ֱ�� and Colleges on coronavirus (COVID-19)

COVID-19 coronavirus vaccine: everything you need to know

Study clears important hurdle towards developing an HIV vaccine