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-بالینی trial in animals. The novel mRNA ژن-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 بالینی trial sponsored by NIAID has started. Another clinical trial sponsored by International AIDS Vaccine Initiative (IAVI) based on Moderna’s mRNA ژن platform based is evaluating HIV vaccine antigens
بیش از 40 سال از اولین گزارش می گذرد اچ آی وی/مورد ایدز در سال 1981. علیرغم تلاش های هماهنگ طولانی مدت جامعه علمی و پزشکی در سراسر جهان، به دلیل چندین چالش از جمله تنوع آنتی ژنی قابل توجه پروتئین پوششی (Env)، واکسن ایمن و موثر علیه HIV/AIDS تاکنون امکان پذیر نشده است. پیکربندی اپی توپ های حفاظت شده و خود واکنشی آنتی بادی ها چندین رویکرد امتحان شد اما نتایج رضایت بخش نبود. فقط یک کارآزمایی انسانی می‌تواند سطح پایینی از حفاظت (~30%) را ارائه دهد.
موفقیت از mRNA ژن vaccines against SARS CoV-2 has opened up the possibility of developing mRNA ژن technology-based vaccines for other pathogenic viruses like Human Immunodeficiency viruses (اچ آی وی) responsible for AIDS. The researchers of NIH’s National Institute of Allergy and Infectious Diseases (NIAID) have recently reported development of a novel mRNA اچ آی وی vaccine which has shown promises in پیش بالینی trials on animals.
The NIAID research team used mRNA ژن for expression of two viral proteins – اچ آی وی-1 envelope (Env) protein and simian immunodeficiency virus (SIV) Gag protein. Injection of mRNA ژن 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. آنتی بادی were formed that could neutralise and reduce the risk of infection (VLPs could not cause infection because of lack of genome of اچ آی وی). 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 ژن واکسن علیه اچ آی وی.
Encouraged by the results, the phase 1 بالینی trial (NCT05217641) has been sponsored by National Institute of Allergy and Infectious Diseases (NIAID), which is currently recruiting participants.
دیگر بالینی trial (NCT05001373) sponsored by International AIDS Vaccine Initiative (IAVI) based on Moderna’s mRNA ژن 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 بالینی آزمایش های، واکسن های mRNA مبارزه با HIV/AIDS ممکن است در آینده نزدیک در دسترس قرار گیرد.
***
منابع:
- Zhang, P., Narayanan, E., Liu, Q. et al. A multiclade env–gag VLP mRNA ژن vaccine elicits tier-2 اچ آی وی-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, اچ آی وی-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 ژن 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 ژن-1644) and Core-g28v2 60mer mRNA Vaccine (mRNA ژن-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
***
