Successful development of mRNA vaccines, BNT162b2 (of Pfizer/BioNTech) and mRNA-1273 (of Moderna) against the novel coronavirus SARS CoV-2 and the important role these vaccines played recently in mass immunisation of people against COVID-19 pandemic in several countries has established RNA technology and is ushering in a new era in medicine and drug delivery. Its application in development of vaccines against other diseases and therapeutics for several diseases including cancer has already began showing early results. Recently, French scientists had reported a proof of concept for the treatment of Charcot-Marie-Tooth disease, the most common hereditary neurological disease that causes progressive paralysis of the legs. In the area of vaccine development, mRNA vaccine candidate against HIV/AIDS is reported to have shown promise in pre-klinisch trial in animals. The novel mRNA-based HIV vaccine was found safe and reduced risk of HIV-like infection in monkeys thus paving way for phase 1 clinical trials. Based on this, a klinisch trial sponsored by NIAID has started. Another clinical trial sponsored by International AIDS Vaccine Initiative (IAVI) based on Moderna’s mRNA platform based is evaluating HIV vaccine antigens
Het is meer dan 40 jaar geleden sinds het eerste rapport van HIV/AIDS-zaak in 1981. Ondanks langdurige gezamenlijke inspanningen van de wetenschappelijke en medische gemeenschap over de hele wereld, is een veilig en effectief vaccin tegen HIV/AIDS tot dusver niet mogelijk geweest vanwege verschillende uitdagingen, waaronder de opmerkelijke antigene variabiliteit van envelop-eiwit (Env), het beschermde configuratie van geconserveerde epitopen en autoreactiviteit van antilichamen. Verschillende benaderingen werden geprobeerd, maar de resultaten waren onbevredigend. Slechts één proef op mensen kon een laag beschermingsniveau bieden (~30%).
succes van mRNA vaccines against SARS CoV-2 has opened up the possibility of developing mRNA technology-based vaccines for other pathogenic viruses like Human Immunodeficiency viruses (HIV) responsible for AIDS. The researchers of NIH’s National Institute of Allergy and Infectious Diseases (NIAID) have recently reported development of a novel mRNA HIV vaccine which has shown promises in preklinisch trials on animals.
The NIAID research team used mRNA for expression of two viral proteins – HIV-1 envelope (Env) protein and simian immunodeficiency virus (SIV) Gag protein. Injection of mRNA in the muscle for expression of these two proteins generated virus-like particles (VLPs) which was able to induce immune response similar to natural infection. Antilichamen were formed that could neutralise and reduce the risk of infection (VLPs could not cause infection because of lack of genome of HIV). Vaccination with both env and gag mRNAs yielded better results. The vaccinated animals had 79% lower risk of infection than the unvaccinated animals. Safety and effectiveness data on animals suggested a promising approach for the development of mRNA vaccin tegen HIV.
Encouraged by the results, the phase 1 klinisch trial (NCT05217641) has been sponsored by National Institute of Allergy and Infectious Diseases (NIAID), which is currently recruiting participants.
Nog een klinisch trial (NCT05001373) sponsored by International AIDS Vaccine Initiative (IAVI) based on Moderna’s mRNA platform is evaluating HIV vaccine antigens originally developed as proteins at Scripps Research and IAVI’s Neutralizing Antibody Center (NAC). This research team had earlier showed that ‘’an adjuvanted protein-based version of the priming immunogen (eOD-GT8 60mer) induced the desired B-cell response in 97% of recipients’’.
Depending on satisfactory safety and effectiveness results from the klinisch beproevingen, mRNA-vaccins tegen HIV/AIDS kunnen in de nabije toekomst beschikbaar komen.
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Referenties:
- Zhang, P., Narayanan, E., Liu, Q. et al. A multiclade env–gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques. Nat Med 27, 2234–2245 (2021). https://doi.org/10.1038/s41591-021-01574-5
- A Clinical Trial to Evaluate the Safety and Immunogenicity of BG505 MD39.3, BG505 MD39.3 gp151, and BG505 MD39.3 gp151 CD4KO HIV Trimer mRNA Vaccines in Healthy, HIV-uninfected Adult Participants – ClinicalTrials.gov Identifier: NCT05217641 Sponsor: National Institute of Allergy and Infectious Diseases (NIAID). Available at https://clinicaltrials.gov/ct2/show/NCT05217641?cond=NCT05217641&draw=2&rank=1
- IAVI – Press Releases – IAVI and Moderna launch trial of HIV vaccine antigens delivered through mRNA technology. Posted January 27, 2022. Available at https://www.iavi.org/news-resources/press-releases/2022/iavi-and-moderna-launch-trial-of-mrna-hiv-vaccine-antigens
- A Phase 1 Study to Evaluate the Safety and Immunogenicity of eOD-GT8 60mer mRNA Vaccine (mRNA-1644) and Core-g28v2 60mer mRNA Vaccine (mRNA-1644v2-Core). ClinicalTrials.gov Identifier: NCT05001373. Sponsor: International AIDS Vaccine Initiative. Available at https://clinicaltrials.gov/ct2/show/NCT05001373?cond=NCT05001373&draw=2&rank=1
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