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-κλινικός 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 κλινικός 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
Έχουν περάσει περισσότερα από 40 χρόνια από την πρώτη έκθεση του Τον ιό HIV/Υπόθεση AIDS το 1981. Παρά τις μακροχρόνιες συντονισμένες προσπάθειες της επιστημονικής και ιατρικής κοινότητας παγκοσμίως, ένα ασφαλές και αποτελεσματικό εμβόλιο κατά του HIV/AIDS δεν έχει καταστεί δυνατό μέχρι στιγμής λόγω πολλών προκλήσεων, συμπεριλαμβανομένης της αξιοσημείωτης αντιγονικής μεταβλητότητας της πρωτεΐνης φακέλου (Env), η προστατευόμενη διαμόρφωση διατηρημένων επιτόπων και αυτοαντιδραστικότητα αντισωμάτων. Δοκιμάστηκαν αρκετές προσεγγίσεις, ωστόσο τα αποτελέσματα δεν ήταν ικανοποιητικά. Μόνο μία δοκιμή σε ανθρώπους θα μπορούσε να προσφέρει χαμηλό επίπεδο προστασίας (~30%).
Επιτυχία του 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 (Τον ιό 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 Τον ιό HIV vaccine which has shown promises in προκλινική trials on animals.
The NIAID research team used mRNA for expression of two viral proteins – Τον ιό 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. Αντισώματα were formed that could neutralise and reduce the risk of infection (VLPs could not cause infection because of lack of genome of Τον ιό 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 Τον ιό HIV.
Encouraged by the results, the phase 1 κλινικός trial (NCT05217641) has been sponsored by National Institute of Allergy and Infectious Diseases (NIAID), which is currently recruiting participants.
Άλλος κλινικός 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 κλινικός δοκιμές, Εμβόλια mRNA κατά του HIV/AIDS ενδέχεται να είναι διαθέσιμα στο εγγύς μέλλον.
***
αναφορές:
- Zhang, P., Narayanan, E., Liu, Q. et al. A multiclade env–gag VLP mRNA vaccine elicits tier-2 Τον ιό 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, Τον ιό 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 – Δελτία Τύπου – Η IAVI και η Moderna ξεκινούν δοκιμή αντιγόνων εμβολίου HIV που παρέχονται μέσω τεχνολογίας mRNA. Δημοσιεύτηκε στις 27 Ιανουαρίου 2022. Διαθέσιμο στο https://www.iavi.org/news-resources/press-releases/2022/iavi-and-moderna-launch-trial-of-mrna-hiv-vaccine-antigens
- Μια μελέτη Φάσης 1 για την αξιολόγηση της ασφάλειας και της ανοσογονικότητας του εμβολίου mRNA 8μερών eOD-GT60 (mRNA-1644) και του εμβολίου 28μερούς mRNA Core-g2v60 (mRNA-1644v2-Core). Αναγνωριστικό ClinicalTrials.gov: NCT05001373. Χορηγός: International AIDS Vaccine Initiative. Διαθέσιμο στο https://clinicaltrials.gov/ct2/show/NCT05001373?cond=NCT05001373&draw=2&rank=1
***
