mRNA vaccine protects macaques after 10 doses of vaccine


Bethesda / Maryland – An mRNA vaccine, which, like COVID-19 vaccines, causes the body’s own cells to produce viral proteins, has reduced the risk of macaques of infection with an HIV-like retrovirus by 79% in an experimental study. Results were in Nature Medicine (2021; DOI: 10.1038 / s41591-021-01574-5) presented.

For several decades all attempts to develop an effective AIDS vaccine have failed. Most recently, a variant of the RV144 combination, which 10 years ago had a protective effect of around 30% in Thailand, was unable to protect younger men from infection in South Africa. Could the mRNA platform, which has proven surprisingly effective against COVID-19, bring the long-awaited breakthrough? Researcher at the US National Institute of Allergy and Infectious Diseases (NIAID) tested a 1st vaccine on mice and monkeys.

With the mRNA platform, vaccines can be designed “on the drawing board” and tested within a short period of time. Since the body cells take over the production, the interruptions and costs that result from the development and production of synthetic vaccines are eliminated. Paolo Lusso’s team was able to implement his idea of ​​a new HIV vaccine relatively quickly and precisely.

The vaccine should not only consist of the envelope protein of the retrovirus, but also be surrounded by a glycan coat like the real virus. The surface proteins should only contain those sections that do not change and therefore induce the formation of permanently neutralizing antibodies. Thirdly, the vaccination should lead to the production of virus-like particles (VLP) that are as similar as possible to the model without being able to multiply in the body. The VLP should therefore not contain any genes of their own. This can also be easily achieved with an mRNA platform. In addition, modified VLPs can be produced for the various individual vaccinations, which could further improve immunity.

The result was a VLP whose core consists of the structural protein “gag”, which has more “env” proteins on the surface than the original HI virus, which it nevertheless resembles on electron microscopic images. In initial experiments, the VLP achieved a better immune response than a vaccine that only consists of the mRNA of the “env” protein against which the antibodies are to be generated.

The vaccine was then tested on macaques. The animals received a total of 8 doses of an mRNA vaccine over the course of 1 year, including 4 heterologous vaccinations that contained the “env” gene of another HIV strain. The “gag” gene came from a simian immunodeficiency virus (SIV), a relative of HIV that infects monkeys. There were also 2 vaccinations with a conventional protein vaccine. At the end of the series of 10 doses, all vaccinated macaques had developed neutralizing antibodies against various strains of HIV. In addition to neutralizing antibodies, the VLP mRNA vaccine also induced a robust T helper cell response.

This created good conditions for the defense against HIV-like viruses, with which the animals were exposed rectally once a week for 13 weeks. While all non-vaccinated animals in a control group became infected within 3 weeks, 2 of 7 vaccinated macaques remained without infection. In the other 5 vaccinated macaques, the onset of infection was significantly delayed. Lusso determines a hazard ratio of 0.21 for the risk of infection per exposure, the 95% confidence interval of which ranges from 0.05 to 0.91. This shows a statistically significant protective effect of 79%, but it could also be 95% or just 9%.

It cannot be predicted whether this will be sufficient for a protective effect in humans. It also appears questionable whether 10 vaccination appointments over a year would be realistic. However, the researchers are confident.

If the safety and efficacy are confirmed in further experiments, a phase 1 study in healthy adult volunteers could soon begin, according to the press release. © rme /


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