mRNA vaccines and broadly neutralising antibodies

mRNA vaccines should induce viral proteins directly in the body and stimulate the immune system to produce broadly neutralising antibodies against HIV.

Requirements for HIV vaccine development

We are currently 40 years since the discovery of the HI virus, and despite numerous advances in the therapy of HIV infection, it has not yet been possible to develop a curative or preventive vaccine against HIV. HIV vaccine research has now been given a new boost by the success of mRNA technology in the case of SARS-CoV-2. But it is still not quite so "simple" with HIV.

The ideal HIV vaccine

Developing a vaccine against HIV is by no means easy. Many of the vaccine candidates tested so far have not been effective in trials and have not conferred any or sufficient protection against the infection. The RV144 trial tested the only candidate vaccine to date that provided at least 31% protection against new infection. A value that is, of course, not sufficient to be further developed as a vaccine.

Moreover, classical antigen-based vaccines are most likely not suitable to induce the necessary sufficient activation of the antibody-based as well as the cellular immune response.

However, an ideal HIV vaccine would need to mount a broadly neutralising antibody response as an initial protection against infection, as well as generate a robust CD8+ T cell response to eliminate the early infected cells. The latter is particularly important to prevent HIV from forming reservoirs.

High HIV mutation rates require high variability in vaccination

One of the biggest problems in HIV vaccine development is the high mutability of the HI virus. The viral reverse transcriptase works with a high error rate, so that mistakes happen when the viral RNA genome is transcribed into DNA. This ultimately leads to the formation of viral variants that carry altered envelope proteins or have lost important glycosylations. This makes it even more difficult for our immune system to consistently follow the virus in order to eliminate it.

Added to this is the fact that the virus integrates into the host cell DNA very quickly after infection. Long-lasting antibody titres with a very broad binding specificity will be necessary to prevent the virus from already entering these target cells.

It is known from current studies that the use of so-called broadly neutralising antibodies (bnAb) can indeed reduce the viral load. However, if antibody administration is discontinued, the virus replicates again and viral titres rise. Currently, bnAb are therefore considered an alternative to active HIV vaccination and are being intensively researched.

Researchers - such as Prof. Barton Haynes from the Duke Human Vaccine Institute and Center for HIV-AIDS Vaccine Immunology in the USA - are also trying to combine the bnAb with a modern mRNA vaccine.

mRNA vaccines that induce broadly neutralising antibodies

The idea: an mRNA vaccine that codes for different protein variants of the HIV envelope proteins. In the muscle cells of the vaccinated, protein variants are created from this mRNA information, which stimulate the immune system to produce a wide range of antibodies. If these antibodies recognise different HIV strains equally, researchers speak of broadly neutralising antibodies (bnAb for short).

In addition, mRNA vaccines offer further advantages over classical protein vaccines

  1. increased safety with regard to a cell-free manufacturing process,
  2. increased efficacy,
  3. simple and fast production and thus also faster adaptation possibilities.

In summary, the properties of mRNA vaccines - their safety, ease of production and ability to encode complex protein designs - make them a prime platform for HIV vaccine development.


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Symposium SY34 „Advances in combatting HIV with broadly neutralizing antibodies”. AIDS 2022, Montreal