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-קליני 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 קליני 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
חלפו יותר מ-40 שנה מאז הדיווח הראשון של HIVמקרה /איידס בשנת 1981. למרות מאמצים ממושכים של הקהילה המדעית והרפואית ברחבי העולם, חיסון בטוח ויעיל נגד HIV/איידס לא היה אפשרי עד כה עקב מספר אתגרים, כולל שונות אנטיגני יוצאת דופן של חלבון המעטפת (Env), המוגן תצורה של אפיטופים שמורים ותגובתיות אוטומטית של נוגדנים. נוסו מספר גישות אולם התוצאות לא היו משביעות רצון. רק ניסוי אנושי אחד יכול להציע רמה נמוכה של הגנה (~30%).
הצלחה של 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 פרה-קליני 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. נוגדנים 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 קליני trial (NCT05217641) has been sponsored by National Institute of Allergy and Infectious Diseases (NIAID), which is currently recruiting participants.
אחר קליני 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 קליני ניסויים, חיסונים mRNA against HIV/AIDS may become available in near future.
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הפניות:
- 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 - הודעות לעיתונות - IAVI ומודרנה משיקים ניסוי של אנטיגנים של חיסון HIV המועברים באמצעות טכנולוגיית mRNA. פורסם ב-27 בינואר 2022. זמין ב https://www.iavi.org/news-resources/press-releases/2022/iavi-and-moderna-launch-trial-of-mrna-hiv-vaccine-antigens
- מחקר שלב 1 להערכת הבטיחות והאימונוגניות של חיסון eOD-GT8 60mer mRNA (mRNA-1644) ו-Core-g28v2 60mer mRNA Vaccine (mRNA-1644v2-Core). מזהה ClinicalTrials.gov: NCT05001373. חסות: יוזמת חיסון נגד איידס בינלאומית. זמין ב https://clinicaltrials.gov/ct2/show/NCT05001373?cond=NCT05001373&draw=2&rank=1
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