University of Cambridge research paves way for effective HIV vaccine

With 36.7 million living with HIV across the world, there is a pressing need for a vaccine. But so far, one that offers lasting protection has eluded scientists.

It is estimated that more than 100,000 people in the UK are living with HIV – 13 per cent of whom are unaware of their condition.

Today, treatment for the virus is highly effective. If diagnosed promptly, a person with HIV in the UK can expect to live into old age.

Free antiretroviral therapy (ART) has transformed HIV over the last two decades from a fatal infection into a chronic, manageable condition – and for many, treatment consists of just one tablet a day, with no or few side effects.

What’s more, a landmark scientific study last year showed that those on effective HIV treatment have such low levels of the virus in their blood that they cannot pass it on.

It means that new infections are driven by those who do not know they are infected – and those who are not on effective treatment.

The picture is very different in some other parts of the world.

Across the globe, an estimated 36.7 million people were living with HIV in 2016 – a rise of 24 per cent from 2001, reflecting a high number of new infections but also the fact that effective treatment has reduced AIDS-related deaths.

Sub-Saharan Africa remains the region most badly affected, with an estimated 25.4 million people living with the virus – more than two-thirds of all cases – in 2015. AIDs has claimed more than a million lives a year in the region since 1998.

The need for a vaccine, then, is still pressing. Its advantages over anti-retroviral drugs are obvious – prevention could lead to the eradication of HIV.

In 2009, a clinical trial in Thailand found that an experimental vaccine against HIV lowered the rate of human infection by 31 per cent.

While promising, there was a significant problem: the vaccine did not offer long-lasting protection because the immune response it generated was very short-lived.

Now, University of Cambridge scientists have helped to discover why – and unlocked a potential solution that gives renewed hope of a long-lasting, effective vaccine.

“For a vaccine to work, its effects need to be long lasting,” says Professor Jonathan Heeney, from Cambridge’s Laboratory of Viral Zoonotics. “It isn’t practical to require people to come back every six-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.”

HIV stands for human immunodeficiency virus. Like all viruses, it replicates itself inside the human body and spreads. But HIV is particularly notorious because it targets the immune system’s master regulators, known as CD4 T-helper cells. These cells produce key signals that prompt other immune cells to swing into action – namely B-cells, which make antibodies and T-killer cells, which destroy cells infected with a virus.

HIV paralyses the body’s immune defences and it does so without even needing to enter or kill the CD4 T-cells. Instead, it binds to them via an important molecule on their surface.

Vaccines aimed at preventing HIV infection have used a form of a protein on the outer coat of the virus, called gp140, to provoke the immune system’s B-cells into producing an antibody response.

But in previous studies the response has only worked for a brief period, which proved insufficient to generate enough antibodies to provide lasting protection against HIV infection.

Prof Heeney, working with scientists in the UK, France, the USA and the Netherlands, identified that the binding of gp140 to a receptor on the CD4 T-helper cells was causing this.

By preventing the protein from attaching to the receptor, this short-term block in antibody producing B-cells could be overcome.

“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 had the time to make all the changes necessary to create the ‘silver bullets’ to stop HIV,” says Prof Heeney. “What we have found is a way to greatly improve B-cell responses to an HIV vaccine.”

Announcing their findings in the Journal of Virology, the researchers demonstrated that they could provoke the immune response needed that was capable of lasting more than a year.

They found that adding a tiny specific protein patch to the gp140 protein stopped it from binding to the receptor. This meant the CD4 T-helper cells could still work and send signals to the antibody-producing B-cells. The B-cells were better able to recognise contours on the coat of the virus, improving the quality of the antibodies.

This small patch was one of a number of strategies employed to improve the use of gp140 in an HIV vaccine by a team led by Susan Barnett, now at the Bill and Melinda Gates Foundation.

The discovery should allow HIV vaccines to be developed that give the immune system sufficient time to develop an effective B-cell response that produces protective antibodies. The team now aims to secure funding to test its vaccine candidate in humans.

Prof Heeney says: “We hope our discovery will unlock the paralysis in the field of HIV vaccine research and enable us to move forward.”

The studies were funded by the US National Institutes of Health and the Isaac Newton Trust in Cambridge.

HIV in Cambridgeshire and the East

There is concern about the number of people diagnosed late with HIV in the East of England.

A Public Health England report released last month said: “HIV remains an important public health problem in the East of England with high and increasing rates of HIV and evidence of sustained HIV transmission in men who have sex with men. “In 2015, an estimated 418 East of England residents were newly diagnosed with HIV.

“It is of particular concern that a large proportion of people with HIV are diagnosed late in the East of England (52 per cent from 2013 to 2015, compared to 40 per cent in England).”

In Cambridgeshire, the proportion diagnosed late – defined by low CD4 count - was 48 per cent.

“People who are diagnosed late have a tenfold risk of mortality within one year of diagnosis compared to those diagnosed promptly and they have increased healthcare costs,” added the report.

Those undiagnosed are also at risk of transmitting the virus to others through unprotected sex.

There were 133 residents in Cambridge aged 15-59 accessing HIV-related care in 2015. East Cambridgeshire had the lowest proportion of people with HIV of any district in the East, with South Cambridgeshire also among the lowest.

PHE said heterosexuals were more likely to be diagnosed late (67% of males, 56% of females) than men who have sex with men (38%). By ethnic group, Black Africans were more likely to be diagnosed late than the white population (64% and 45% respectively).

The diagnosis rate for over-15s in the East was eight per 100,000, compared to 12 per 100,000 across England. Heterosexual contact was the largest route of infection for those newly diagnosed in the East during 2015 (57%). Infections in African-born people accounted for 49% of heterosexually-acquired cases, while 30% of patients were born in the UK.

Some 97% of the 16,846 people known to have HIV in the East of England and the Midlands in 2015 were receiving anti-retroviral therapy.