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Could we mass-produce HIV immunity?

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South Africa should be proud: of the more than six million people living with HIV in the country today, 3.4-million are on antiretroviral treatment, according to the department of health. But millions more will need treatment unless we stop new infections. One tiny protein may be the world’s best hope of halting HIV in its tracks.

South Africa continues to bear the brunt of the HIV pandemic and increasing numbers of people living with the virus are in need of treatment. Meeting this need has its costs: by 2033, about R40-billion a year will be required to finance the HIV programme, according to the country’s investment case study report by the South African National Aids Council.

High costs are just one reason that, in the long-term, continued large-scale HIV treatment is unrealistic.

An HIV vaccine is the best hope for ending the pandemic, but creating one has been a daunting challenge for more than three decades.

Now, two large clinical trials in South Africa and recent ground-breaking scientific advances are taking us closer to this goal.

One strategy builds on a 2009 Thai clinical trial in which an HIV vaccine reduced HIV infection rates among participants by about 31%. The vaccine worked much like the common polio vaccine does, tricking the body into thinking that HIV was present in participants’ bloodstreams. The body then reacted by producing antibodies, or proteins used by the immune system to fight off bacteria or viruses like HIV.

Although the Thai vaccine trial did not prevent enough infections to allow the vaccine to be marketed, it was the first trial to indicate that an HIV vaccine was possible. An improved version of this vaccine, tailor-made for the HIV strain found in South Africa, is being tested among 5 400 men and women. Researchers are hoping it will halve new HIV infections among participants by 2021.

But a different approach to an HIV vaccine relies on unusual superantibodies called  “broadly neutralising antibodies”. These antibodies can kill variants of HIV from across the world. Many scientists believe these types of proteins might provide even better protection against HIV infection than those found in the Thai trial.

South African studies have been able to identify some people who produce these superantibodies naturally. Recent scientific breakthroughs at several United States laboratories now suggest that in the future we may be able to make “smart vaccines” that will trigger our bodies’ ability to make broadly neutralising antibodies.

In the meantime, we can replicate and mass-produce these antibodies in ultraclean factories. These laboratory-made superantibodies could then be administered to people via intravenous drips in an approach being tested out now in six African countries, including South Africa, Kenya and Mozambique.

This approach, called passive immunisation, has been used for more than 100 years to treat viruses such as rabies, but it has only recently become an option for HIV. As part of the six-country clinical trial, 1 500 HIV-negative women at high risk of contracting the virus will receive an antibody infusion every two months for 20 months.

Participants also receive counselling on how to prevent HIV infection generally, including how to practise safer sex and the benefits of pre-exposure prophylaxis (PrEP). As part of PrEP, high-risk HIV-negative people take a daily combination of antiretrovirals to avoid contracting the virus.

The trial is unprecedented in HIV prevention research and involves an enormous multidisciplinary team of committed researchers from across the globe.

If the study can show that the antibody infusions led to fewer infections among women, it will provide the first evidence that these types of antibodies can protect humans from HIV infection.

If passive immunisation works, as it has in monkeys, it will change the landscape of HIV prevention research. It may also change treatment, enabling HIV doctors to follow in the footsteps of cancer researchers and rheumatologists, who routinely use antibodies to treat cancer and autoimmune conditions.

It is an enormously hopeful time for HIV vaccine development and South Africa is playing a leading role in not only vaccine trials but also in the basic laboratory research that underpins them.

But the results of these trials will take years. Now, we must continue to use other HIV prevention tools to reduce the number of new HIV infections, particularly in vulnerable populations such as young women, who continue to be most heavily affected.

Penny Moore is a reader and South African research chair of Virus-Host Dynamics at the University of the Witwatersrand. Lynn Morris heads the HIV virology section in the Centre of HIV and Sexually Transmitted Infections at the National Institute for Communicable Diseases (NICD) in Johannesburg. Nono Mkhize is a senior medical scientist at the NICD

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