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
Seit dem ersten Bericht von sind mehr als 40 Jahre vergangen HIV/AIDS-Fall im Jahr 1981. Trotz langer konzertierter Bemühungen der wissenschaftlichen und medizinischen Gemeinschaft weltweit war ein sicherer und wirksamer Impfstoff gegen HIV/AIDS bisher aufgrund mehrerer Herausforderungen, einschließlich der bemerkenswerten antigenen Variabilität des Hüllproteins (Env), des geschützten, nicht möglich Konfiguration konservierter Epitope und Autoreaktivität von Antikörpern. Es wurden mehrere Ansätze ausprobiert, die Ergebnisse waren jedoch unbefriedigend. Nur eine Humanstudie konnte ein geringes Schutzniveau bieten (~30 %).
Erfolg von 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 präklinisch 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. Antikörper 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 vaccine against 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.
Ein anderer 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 Versuche, mRNA-Impfstoffe gegen HIV/AIDS könnten in naher Zukunft verfügbar sein.
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References:
- 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 – Pressemitteilungen – IAVI und Moderna starten Versuch mit HIV-Impfstoff-Antigenen, die durch mRNA-Technologie geliefert werden. Gepostet am 27. Januar 2022. Verfügbar unter https://www.iavi.org/news-resources/press-releases/2022/iavi-and-moderna-launch-trial-of-mrna-hiv-vaccine-antigens
- Eine Phase-1-Studie zur Bewertung der Sicherheit und Immunogenität des 8-mer-mRNA-Impfstoffs eOD-GT60 (mRNA-1644) und des 28-mer-mRNA-Impfstoffs Core-g2v60 (mRNA-1644v2-Core). ClinicalTrials.gov-Kennung: NCT05001373. Sponsor: Internationale AIDS-Impfstoff-Initiative. Verfügbar um https://clinicaltrials.gov/ct2/show/NCT05001373?cond=NCT05001373&draw=2&rank=1
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