As of 2020, more than 37 million people across the globe are living with the human immunodeficiency virus (HIV), 1.7 million of which are younger than 15 years. Each year, World AIDS Day takes place on December 1 to commemorate the lives lost to this ongoing global epidemic and help raise awareness for the urgent need to stop HIV. Despite several advances, a cure for HIV remains elusive and many attempts to develop an efficacious HIV vaccine have failed due to the virus’ unique features. Sven Kratochvil and Sarah Wettstadt explain for the #FEMSmicroBlog how advancements in vaccine research from the Covid-19 pandemic might help us tackle the AIDS epidemic. #MicrobiologyEvents

 

HIV escapes the immune system

To develop a vaccine against HIV, the scientific challenges are enormous. The high sequence diversity, HIV’s capacity to evade adaptive immune responses and the early establishment of latent viral reservoirs allow HIV to persist. If left untreated, HIV can weaken a person’s immune system and cause acquired immunodeficiency syndrome (AIDS) leaving patients highly susceptible to opportunistic infections.

Early on, research found that some HIV-infected patients develop broadly neutralising antibodies. These can evolve slowly over a period of time in a patient and can neutralise up to 98 % of HIV isolates.

To better understand the interactions between HIV and this part of the human immune response, some research groups applied structural biology approaches. They found that broadly neutralising antibodies target several sites in an HIV envelope protein.

Since this envelope complex mediates viral entry into white blood cells–T cells–, it is considered a major target for vaccine development. It is, however, by no means an easy target. Not only is the envelope complex highly variable due to a high mutation rate of the coding gene, but it is also heavily glycosylated, further shielding the virus and enabling immunoevasion.

For now, the quest for an HIV vaccine remains elusive. Yet, ongoing HIV vaccine research has led to major discoveries and yielded technological advances in the vaccine development field. This long-term progress is the reason why we now stand a chance in the fight against SARS-CoV-2.

 

The quest for an HIV vaccine leads to RNAissance

Identifying suitable vaccine targets to teach the human immune system to recognize pathogens like viruses is just part of the HIV vaccine quest. At the same time, the mode of vaccine delivery needs to be optimised.

Traditionally, vaccines containing inactivated or weakened virus have been used to protect the population. Yet, this strategy is not always applicable or scalable and might be too risky for viruses such as HIV. To overcome this bottleneck, researchers have and continue to develop new vaccine strategies comprising recombinant subunit vaccines, DNA vaccines and non-replicating vectors.

mRNA vaccines–this radically new approach has come to the attention of our global consciousness. For long, mRNA was considered too fragile and unstable to work with. Only thanks to a chance encounter between an HIV vaccine researcher and a scientist with a talent for mRNA manipulation, we could advance the mRNA-vaccine delivery platform over the last few years.

mRNA vaccines as a new approach has come to the attention of our global consciousness.

One problem of mRNA-based vaccines was that they induce inflammation since the innate immune system recognises the RNA molecule. However, the two vaccine researchers Dr Katalin Karikó and Dr Drew Weissman found that the immunogenicity and potency of mRNA could be modulated.

All they needed to do was to replace the uridine in the RNA molecule with pseudo-uridine. When they then extended the mRNA with a poly-A tail, translation of the immunogen was further increased–making mRNA a unique and rapidly adaptable tool for expressing proteins of interest and particularly immunogens both in vivo and in vitro.

Another quest was to protect the mRNA from degradation and transport it into the cytosol of the host cell. Here, lipid nanoparticles came to the rescue. These efficiently encapsulate the mRNA while also strengthening the immune response.

 

An mRNA vaccine to fight them all

Using this novel vaccine platform, Karikó and Weissman developed mRNA-based vaccines packaged in lipid nanoparticles. While vaccines for ZIKA virus, HIV and Influenza were all at different stages in clinical trials pre-Covid-19, the vaccine delivery platform itself was just about optimised when SARS-CoV-2 hit.

Hence, developing, testing and producing the Covid-19 vaccines used by Moderna and Pfizer/BioNTech could be streamlined fast using the available technologies. Like this, we now have first-hand experience with the efficiency of mRNA-based vaccines.

Looking at the fight against HIV; we have learned a lot about mRNA vaccine development from the current Covid-19-pandemic. So, let’s hope we can use these hard lessons to accelerate finding a solution for the HIV challenge as well as stopping future epidemics and even pandemics.

While new infectious diseases emerge almost on a regular schedule, we are still in the middle of our battle against HIV.

Sven Kratochvil, PhD.

 

About the authors

Dr Sarah Wettstadt is a microbiologist-turned science writer and communicator working on various outreach projects and helping researchers talk and write about their scientific results. Her overall vision is to empower through learning: she shares scientific knowledge with both scientists and non-scientists and coaches scientists in writing about their research. Sarah is blog commissioner for the FEMSmicroBlog and was a social media editor for FEMS for 1.5 years. Previous to her science communication career, she worked as a postdoc in Marían Llamas’ lab on Pseudomonas aeruginosa’s ability to use heterologous iron sources and completed her PhD with Alain Filloux investigating the type 6 secretion system in Pseudomonas aeruginosa.

Sven Kratochvil is a vaccine immunologist with a background in clinical research in the Batista Lab at the Ragon Institute at Harvard Medical School. He is passionate about applying new scientific approaches to the study of infectious diseases and the identification of promising vaccine candidates for pre-and clinical evaluation.

About this blog section

The section #MicrobiologyEvents for the #FEMSmicroBlog reports about events and meetings relevant to our network. These include world awareness days, FEMS-sponsored meetings or meetings of Member Societies and many more.

Do you want to be a guest contributor?

The #FEMSmicroBlog welcomes external bloggers, writers and SciComm enthusiasts. Get in touch if you want to share your idea for a blog entry with us!

Back to top