Smallpox has been eradicated from the face of the Earth following a highly effective, worldwide vaccination campaign. Paralytic poliomyelitis is no longer a problem in most parts of the world mainly because of the development and use of effective vaccines against the polio virus.

As we speak, millions of lives are being saved because of the rapid, coordinated administration of effective vaccines against COVID-19. And yet, it has been over 38 years since HIV was discovered as the cause of AIDS, but there is still no vaccine to give to people.

It is natural to wonder why, because to a lot of people this makes no sense. And trust me, I get this question from those I interact with almost every single day of my existence since I started studying medicine. Let me try to clarify a bit, the difficulties facing the development of an effective vaccine against HIV/AIDS.

For decades, vaccines have undoubtedly been society’s most reliable arsenal against viral diseases of medical importance. When AIDS first introduced itself in the early 1980s and the virus that caused it (HIV) was discovered in 1983-84, it was only natural to think that the research community would be able to develop a vaccine for it.

The then U.S. Secretary of Health and Human Services, Margaret Heckler, predicted that a vaccine would be available in two years. I guess she had not yet any idea how complicated the entire situation would be. Well, it is now 38 years later and there is no vaccine. When you look at how rapid the development and distribution of the COVID-19 vaccine has been, in such a short period of time, you just can’t help but wonder why the same has not happened with HIV. Well, the problem is not a failure of the government.

It is not a lack of spending. The problem lies in the HIV virus itself. In particular, this includes the remarkable HIV strain diversity and the immune evasion strategies of the virus. I personally call it the smartest virus to ever exist.

There have so far been five (5) large-scale Phase 3 HIV vaccine trials that have been carried out, each costing at least USD 100 million. The first 3 were horrendous failures as none of them demonstrated any protection against acquisition of the virus, no lowering of viral loads in those who got infected.

The 4th trial (published in 2012) initially reported a small degree of protection against the acquisition of HIV infection among vaccinated individuals. A subsequent statistical analysis was then carried out and reported a less than 78 percent chance that the protection was real.

A 5th trial then got initiated to try and confirm the results of that 4th trial, but it too failed dismally.

What exactly is the problem? The HIV virus itself is the problem. That is the shortest possible answer I can give you. What do I mean? The virus has evolved some biological properties that make the development of a successful vaccine very, very, very difficult. First and foremost is the continuous unrelenting virus replication.

Once HIV gets its foot in the door, there’s practically no going back. Many vaccines do not protect absolutely against the acquisition of an infection, but they are able to severely limit the replication of the virus and any illness that might result.

This means that for a vaccine to be effective against HIV, it will likely need to provide an absolute sterilising barrier and not just limit viral replication. That has proven impossible so far. The second property; the HIV virus has evolved an ability to generate and tolerate many mutations in its genetic information. This has resulted in the HIV strain having too many variations not only from one individual to another but even within a single individual. As of now, we do not yet have any vaccine that is able to work against that many variations.

The third property; it has also evolved a shockingly incredible ability to shield itself from recognition by antibodies (masole a mmele). On their surfaces, enveloped viruses such as coronaviruses and herpes viruses encode a structure that each virus uses to gain entry into a host cell. This structure, composed of both sugars and proteins, is called a glycoprotein.

But the HIV envelope glycoprotein is extreme. It is the most heavily sugared protein of all viruses in all the 22 families of enveloped viruses. More than half the weight is sugar. And the virus has evolved by natural selection, to use these sugars as shields to protect itself from recognition by antibodies that the infected host is trying to make.

The host cell adds these sugars and then views them as self. This means that our antibodies are unable to recognise the virus in our blood.

These properties seriously hamper any efforts to develop a vaccine against HIV. The antibodies that an HIV-infected person makes typically have only very weak neutralising activity against the virus. Furthermore, these antibodies are very strain-specific; they will neutralise the strain with which the individual is infected but not the thousands and thousands of other strains circulating in the population or a community.

The little bit of good news is that researchers already know how to elicit antibodies that will neutralise one strain, but the bad news is that they do not yet know how to elicit antibodies that have the ability to protect against the thousands and thousands of strains circulating in the population. That’s a major problem for vaccine development efforts.

However, HIV research continues and hopefully, we will come up with something soon. At the moment, scientists are working on some approaches which they are currently testing on animal models. I will talk about that in next week’s edition.

Have a healthy weekend everyone. One Health.

Kenneth T. Photlokwe MSc Medicine (Vaccinology) – Wits SANBio Youth Ambassador Email: [email protected] Facebook: Kenneth T. Photlokwe Twitter: @Kenny_TP