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As COVID-19 vaccination begins around the world, UNAIDS spoke to Peter Godfrey-Faussett, UNAIDS Senior Science Adviser and Professor of International Health and Infectious Diseases at the London School of Hygiene and Tropical Medicine, about what is holding up an HIV vaccine.

Many people are asking, “How was a COVID-19 vaccine found so quickly?”

The SARS-CoV-2 virus, which is the virus that causes COVID-19, jumped from animals into humans in 2019. Whereas for HIV, that jump occurred 100 years ago in around the 1920s, and it became a problem in the 1980s when it started spreading among humans to a much greater extent.

The reason we’ve seen such a push on the COVID-19 vaccine is because of the urgency. In 2020, COVID-19 has infected almost 100 million people on the planet. COVID-19 has already killed 2 million people in 2020.

So, this urgency comes about, despite the fact that we’ve seen dramatic changes in everybody’s life, with changes to travel and social distancing and masks and hand washing and sanitizer, and yet we've still seen a rapid rise in infections. This produces a huge urgency to make a vaccine. And, of course, it has a massive economic impact.

HIV and SARS-CoV-2 are quite different, right?

There are fundamental differences between SARS-CoV-2 and HIV. Although they are both viruses, SARS-CoV-2 is a very simple infection. The disease can be complicated, and sometimes mysterious, but almost everyone infected with SARS-CoV-2 develops antibodies to the spike protein and this neutralizes the virus and leads to recovery with a clearance of the virus.

In contrast, almost everybody infected by HIV develops antibodies and we use those antibodies in regular HIV tests. But, unfortunately, very few clear the infection and those antibodies are not sufficient to neutralize the HIV. The HIV envelope, which is more or less like a spike, is a complex structure on the surface of the virus. It’s coated with sugars and the active site is deep inside, so it’s hard to engage with it.

Over time, as people are infected with HIV some people do develop antibodies able to neutralize HIV, but that can take many years, and furthermore HIV is a retrovirus—that’s why we talk about antiretrovirals. A retrovirus is a virus that copies its genetic code and integrates it into the human genetic code. And as it copies, it copies its genetic code, but it doesn’t do it accurately, it makes many mistakes. What that means is that the envelope protein and the HIV itself is constantly changing, shifting its shape, making it difficult for antibodies to protect against it, so even the neutralizing antibodies from one individual often fail to neutralize the virus from a different individual.

We have now found some so-called broadly neutralizing antibodies, as in antibodies that neutralize many different strains of HIV. And those are the antibodies that people are studying at the moment and trying to see whether or not they protect people from catching different strains of HIV. They could be an important part of the process for developing a vaccine against HIV if we could get broader neutralizing antibodies to be generated before the HIV infection occurred.

Finally, we have to remember that, unlike COVID-19, or maybe partly unlike COVID-19, HIV depends a lot on T-cells—the other half of the human defence system. The human immune system has antibodies, but it also has so-called cellular immunity, which is led by T-cells, and that’s much harder to study and much more varied and it also makes HIV difficult and different from COVID-19 when it comes to developing a vaccine.

How much money is being invested in HIV vaccines?

Each year for the past decade we’ve invested around US$ 1 billion in research and development to try to produce an HIV vaccine. Is that a lot or is it not enough? It’s about 5% of the global HIV response budget. There has been some limited success.  Back in 2009 there was great excitement when a vaccine candidate in Thailand did produce some protection against HIV infection, but not enough for it to be taken into widescale production.

And then over the next decade, subsequent trials have taught us a lot about the immunology, about the way human bodies and immune systems interact with HIV, but they haven’t led to a reduction in new HIV infections. Hope is currently resting on two large studies that are in the field at the moment, and there are many other candidates in the pipeline. So, I think there is hope, but we clearly won’t have a vaccine in the short term in the way that we have with COVID-19.

COVID-19 has taken the headlines—what about other infectious diseases?

In Africa, tuberculosis, malaria and HIV each kill more than five times as many people per year as COVID-19 has killed in Africa this year. These are huge problems and they've been going on for a long time. We have a vaccine against tuberculosis, the BCG vaccine, first used 100 years ago, starting in 1920, but unfortunately it doesn't really protect against the common adult forms of tuberculosis. Just recently, new vaccines have been discovered against both tuberculosis and malaria, but they don’t work particularly well. There are discussions about whether to scale them up because they only have a protective efficacy of 30% or less.

The good news is that a new malaria vaccine has just gone into big phase three trials in Africa, and in fact it’s produced by the same setup that has produced the AstraZeneca Oxford COVID-19 vaccine, so the hope is that the research that’s being done on COVID-19 vaccines may act as a shot in the arm for all the other important infectious disease killers that actually kill many, many more people in Africa and other resource-constrained parts of the world.

Watch: UNAIDS Science Adviser explains some differences between HIV and COVID-19