mRNA vaccines: Could they be as effective for HIV as they are for COVID-19?

Nobody can have missed the fact that a new type of vaccine has had tremendous success against SARS-CoV-2, the virus that causes COVID-19.

At this time last year, the only tools that we had to reduce the spread of this virus were physical measures such as masks, physical distancing and quarantine. Now, the largest question facing us is how to end the pandemic faster by encouraging the uptake of highly effective COVID-19 vaccines. In Canada, both of the vaccines currently available to us are a new type of vaccine, known as mRNA vaccines.

How mRNA vaccines work

When a virus infects a target cell, it first induces that cell to produce messenger RNA (mRNA). This mRNA is like a blueprint that codes for the cell to make virus proteins, which are then assembled to make new viruses.

Some past vaccines have used a weakened virus (for example, chicken pox and measles vaccines). When this vaccine is injected into a person, it infects a small number of cells – too few to make the person sick, but enough that the cells produce virus mRNA and then the virus proteins to induce immune responses. Other vaccines (like the hepatitis B and pneumonia vaccines) use non-infectious virus proteins to induce the immune responses.

So where do the new mRNA vaccines fit in? Basically, they are halfway between these two strategies: they insert the mRNA that codes for virus proteins, so that our cells can make virus proteins without the need to use any actual infectious virus. When the mRNA in the vaccine codes for the surface proteins of the SARS-CoV-2 virus, this induces robust immune responses that strongly protect the person against infection, and even more strongly against severe COVID-19 illness.

mRNA vaccines for HIV

So – if the mRNA that was used in the vaccine coded for HIV surface proteins instead, would this protect against HIV in the same way? The short answer is that we do not know, but the possibility is already being tested in early clinical trials. An mRNA vaccine strategy targeting an HIV-like virus did show promise in models in monkeys, where antibodies could be induced against the part of the HIV envelope that binds to CD4 cells, and this reduced the risk of monkeys getting infected with the HIV-like virus.

However, it is important to remember that compared to COVID-19, we know much less about the type of immune response that can protect against HIV. All people living with HIV are infected life-long, even though we make strong immune responses against HIV after infection. This is very different from COVID-19, where the antibodies induced by infection usually lead to clearance of the SARS-CoV-2 virus within a few days and recovery of health, and where the persistence of these antibodies over time is strongly protective against getting infected again. Therefore, even if an mRNA vaccine strategy can induce strong immune responses against HIV without the need for using a “weakened” form of the virus, we still do not have a clear understanding of which parts of the virus those immune responses should target.

The promise of mRNA vaccines

In fact, an HIV vaccine tested a few years ago that was based on inserting HIV genes into an adenovirus (a similar approach to that used by other effective vaccines against COVID-19) actually increased the risk of a vaccinated person getting infected by HIV. Therefore, it does not seem that all vaccine strategies used to make a successful COVID-19 vaccine will necessarily translate into success against HIV.

The bottom line is that mRNA vaccines are a very safe way to induce strong immune responses against viruses. They can easily be adapted to target different viruses other than the coronavirus that causes COVID-19, and early safety trials of mRNA-based HIV vaccines are already underway.

We can and should be hopeful about the promise of these mRNA vaccines, but in the meantime, we should remember that we already have excellent and highly effective ways to prevent HIV available to us right now, including condoms, pre-exposure prophylaxis (PrEP) for people at risk of HIV and highly effective antiretroviral treatment for people living with HIV.

Dr. Rupert Kaul is a professor and director of the Division of Infectious Diseases at the University of Toronto and the University Health Network/Mount Sinai Hospital. Dr. Kaul became interested in HIV research soon after completing his infectious disease clinical training. Today, Dr. Kaul’s research investigates how genital immunology and the microbiome affect HIV susceptibility and transmission in cohorts of people from Canada, Uganda and Kenya.