Where is the HIV Vaccine?

Earlier this month, something happened.

I was listening to my health teacher go on about the dangers of STIs and don’t get me wrong, I was listening to every word. But there was one type of STI that struck me differently.

There are sicknesses you’ve never heard of, thanks to vaccines. Smallpox was eradicated in 1977. Polio no longer exists in the majority of the world, thanks to the Polio Eradication Organization. Some of us will even go through an immunization schedule for the first 15 months of our lives, filled with vaccines for viruses you can’t pronounce and have never heard of.

But if you have HIV, you’re out of luck. Because there is no known cure, there are no vaccines.

This statement led me on a spiral to understand viruses. Why is it so hard to create vaccines for certain viruses? And if an HIV vaccine can never exist, what do we do?

And so, are we on a roller coaster? Because it’s about to go down.

  • Why is HIV a threat?
  • How is HIV different than other viruses?
  • What now?

HIV: the silent killer

Human Immunodeficiency Virus (HIV) is a sexually transmitted infection. By the end of 2019, 38 million people in the world were living with HIV, and a remaining 7.1 million people were living with HIV, but didn’t know.

HIV doesn’t discriminate against age, newborns can contract HIV from their birthmothers. People who contract HIV need to take antiretroviral therapy (ART, which we’ll discuss later) for the rest of their lives because there is still no known cure.

Starting 2020, HIV response will cost US taxpayers 28 billion dollars per year. This number will only increase because our global population continues to grow- so does the number of HIV infections.

And so, how does this supreme-virus, 60x smaller than a red blood cell manage to dig a hole this big? Let’s start with the basics.

Virology 101

There are 10 million times more viruses than there are stars in the universe. If you put all these viruses on top of each other, they would reach beyond the moon, beyond the sun and eventually reach a height of 200 million light years. (Yes, viruses are still smaller than our red blood cells.)

These little guys aren’t exactly friendly either. There are four things on a virus’ mind: enter, replicate, release, repeat.

Viruses and host cells are like you and Lego. All the individual pieces for building your rocket ship come in a nice box with the instructions, and by following the instructions you can build your rocket ship. Then you can also reuse those instructions and build more and more rocket ships until you have millions of duplicates of the same rocket ship.

  1. Attachment — the virus uses little spikes (AKA viral proteins) on the host cell’s surface to bind with the cell
  2. Entry — virus enters the host cell and the capsid (where all the virus’ instructions are held, AKA DNA) is brought to the nucleus of the cell, where the DNA is placed
  3. Replication — the viral DNA is recognized by ribosomes in the cell nucleus, they read the DNA and make viral proteins, the pieces we’ll need to build more viruses
  4. Assembly — all the viral proteins come together and new duplicates of the original virus cell are made
  5. Release — an army of replicated viruses are released into the wild, to find their next victim

If you haven’t heard of deoxyribonucleic acid (DNA) or their cousin, ribonucleic acid (RNA) they are the building blocks of all cells.

DNA and RNA are made of monomers, called nucleotides. These nucleotides are made of a phosphate, a sugar and a base. DNA is made with deoxyribose sugar with bases are adenine, guanine, thymine and, cytosine. But for RNA’s nucleotides are made with ribose sugar and bases are adenine, guanine, uracil and cytosine.

Each of these bases will only pair with another specific base. For DNA, adenine will only pair with thymine and guanine will only pair with cytosine. In RNA, uracil pairs with adenine while guanine still pairs with cytosine.

This makes a translator enzyme like RNA polymerase’s job easy(ish) when turning DNA into RNA. Every time it encounters an adenine base, BAM uracil. If it encounters a guanine base, BOOM cytosine.

The flow of information throughout the cell is called the central dogma. DNA is turned into mRNA which is then turned into cute, helpful proteins.

What the virus does first once in the cell all depends on what instructions it comes with. Viruses that come with a full set of perfect DNA, will start making mRNA and then viral proteins. Other viruses will carry RNA, so they immediately start making viral proteins, like the coronavirus.

Here’s what makes HIV special

A super simplified look at a HIV virus.

HIV is a retrovirus, which are a group of viruses that start out with RNA in a little capsid made of proteins. Their RNA is then copied into DNA and hide within the DNA of their host cell in the nucleus.

I’ll explain, HIV starts with 2 positive strands of RNA and uses a little enzyme called reverse transcriptase which turns the RNA into a negative strand of DNA and then back into the positive strand of DNA to complete the set.

This DNA is integrated into the host cell’s nucleus, and then made into positive RNA, then mRNA to make proteins.

Everyone has two parts to their immune system: adaptive immunity and our innate immunity. Innate immunity provides immediate protection but this isn’t always effective because not all pathogens entering our body are the same. Adaptive immunity takes longer to kick in but it’s more powerful and has a crazy memory.

I’m going to focus more on adaptive immunity but that doesn’t make innate immunity any less important.

You can think of our adaptive immunity like the longer-term part of our immune system, these guys remember every virus we’ve ever encountered and extremely powerful. The key players here are T-Cells and B-Cells.

The HIV virus attacks our T-Cells for breakfast.

When proteins are made in our cells, small copy proteins are made and sent to the major histocompatibility complex (MHC) which are little indicators on the cell surface. If the MHC aren’t displaying newly made “self” proteins, T-Cells immediately notice and eliminate the cell.

When our T-Cells are infected with HIV, it doesn’t automatically wait for ribosomes to come and make viral proteins. Remember, HIV viruses are retroviruses so instead, HIV DNA becomes integrated into the the T-Cell’s DNA.

Then T-Cells start producing viral proteins, which are displayed on the MHC. Now it becomes a T-Cell frenzy, healthy T-Cells kill the infected T-Cells who’s MHC aren’t displaying “self” proteins.

Although T-Cells will usually die while HIV spread throughout our immune system, some T-Cells will stay alive. But that doesn’t mean HIV’s DNA is gone, it’s just… taking a break. This means every time a T-Cell undergoes cell division, it will have HIV’s DNA and could attack at any time.

So if another virus comes back for round two, adaptive immunity should be able to kick in! Well, not if the T-Cells are infected with HIV then our immune system becomes compromised. (That’s why its called immunodeficiency.)

Having an HIV infection is like taking a final you didn’t study for. You feel super nervous and scared right before taking the final. But while you’re going through the questions you’re thinking “Ok, I remember this I can do this” and let your guard down. Then right after the final you remember all the mistakes you made, and feel even worse than you did before.

Most people with HIV infection first start out with fever, swollen lymph nodes and diarrhea. Then comes the asymptomatic period, where your T-Cells start to regain their momentum and seems like all is well. Then the HIV virus opens a can of whoop-ass on your immune system, this is when HIV progresses into acquired immunodeficiency syndrome (AIDS)

How do Vaccines factor in?

Vaccines work by prepping our adaptive immunity. Similar to the way you study before a test, vaccines help your adaptive immunity prep for incoming pathogens. So when they do enter your body, you’ll be ready.

Vaccines are little cocktails of viral protein fragments and /or deactivated viruses. They are injected into our blood stream so our B-Cells can start making the perfect antibodies through trial and error. Different viruses need different antibodies, finding the right one can take up to two weeks.

When you get your flu shot, the vaccine contains inactivated influenza (flu) viruses. Inactivated viruses look the same, but they can’t replicate. B-Cells train using the inactivated influenza viruses to prep for flu season. Cool right?

Now here comes the good part…

because not only does HIV like to hide in the DNA of our T-Cell’s nucleus, it’s cellular receptors also mutate very quickly. This means by the time our B-Cells come up with the right antibodies, it’s too late.

HIV is also a diverse virus, there are many different strands of HIV virus. Which means we would have to make a separate vaccine for each one. This would take years and by the time we do come up with the perfect vaccine, HIV has already mutated.

Countries that have poor health infrastructure will likely continue to allow HIV to mutate, so we’ll never be able to catch it. This is why so many countries have contributed money to help build awareness and allow patients to receive treatment for HIV, so it doesn’t progress into AIDS.

So… what do we do now?

Although we might now be able to combat HIV with our traditional vaccines, cool new technologies are creating new ways we can combat HIV.

Instead of building immunity towards HIV, we can stop the transmission of HIV instead. This would slow the mutation rate of HIV and allow infection rates to slowly die off.

Treatment for people who are tested positive for HIV is key. The treatment is called antiretroviral therapy (ART) and is a combination of drugs that fight different aspects of HIV infection. Like stopping HIV from infecting immune cells or preventing HIV from replicating

One acronym, two words. Pre-Exposure Prophylaxis (PrEP) which prevents HIV infection. PrEP is part of ART, but treats people who are at risk for HIV but haven’t been infected. PrEP reduces the chance of getting HIV by at least 74%. It gradually accumulates in your body and protects your cells from HIV.

We need both ART and PrEP if we’re going to beat HIV. But ART and PrEP are not where we need it the most. There are still countries where very few people get this treatment. This is good news for HIV, not so much for us. That is why the US and Canadian government donate so much to HIV-related action funds.

It is estimated that in order to stop the AIDS epidemic by 2030, we will need to invest USD $9 billion more into HIV action funds than we to today. This would total to USD $30 billion by 2030, in order to reduce the amount of HIV infections by 90%.

An HIV-free world is closer than we think. And although HIV may be incurable, it sure is preventable. So maybe we don’t need to search for the HIV vaccines, we just need outreach and collaboration.

Takeaways

  • There is no cure for HIV
  • HIV infects our T-Cells and like to hide in our DNA
  • We can slow the spread of HIV through reactive and proactive treatment

Still Interested?

Here are some other goodies you can check out!

Hi, it’s Isabelle! I’m always looking at the coolest things and currently obsessed with viruses! Subscribe to my newsletter here or connect with me on LinkedIn here!

--

--

16 y/o learner

Get the Medium app

A button that says 'Download on the App Store', and if clicked it will lead you to the iOS App store
A button that says 'Get it on, Google Play', and if clicked it will lead you to the Google Play store