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 РНК 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-клінічний trial in animals. The novel мРНК-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 клінічний trial sponsored by NIAID has started. Another clinical trial sponsored by International AIDS Vaccine Initiative (IAVI) based on Moderna’s мРНК platform based is evaluating HIV vaccine antigens
Минуло понад 40 років з моменту першого звіту про ВІЛ/випадок СНІДу в 1981 році. Незважаючи на тривалі узгоджені зусилля наукової та медичної спільноти в усьому світі, безпечна та ефективна вакцина проти ВІЛ/СНІДу досі не була можлива через декілька проблем, включаючи чудову антигенну мінливість білка оболонки (Env), захищеного конфігурація консервативних епітопів і аутореактивність антитіл. Було випробувано кілька підходів, але результати були незадовільними. Лише одне випробування на людях могло запропонувати низький рівень захисту (~30%).
Успіх мРНК vaccines against SARS CoV-2 has opened up the possibility of developing мРНК technology-based vaccines for other pathogenic viruses like Human Immunodeficiency viruses (ВІЛ) responsible for AIDS. The researchers of NIH’s National Institute of Allergy and Infectious Diseases (NIAID) have recently reported development of a novel mRNA ВІЛ vaccine which has shown promises in доклінічний trials on animals.
The NIAID research team used мРНК for expression of two viral proteins – ВІЛ-1 envelope (Env) protein and simian immunodeficiency virus (SIV) Gag protein. Injection of мРНК 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. антитіла were formed that could neutralise and reduce the risk of infection (VLPs could not cause infection because of lack of genome of ВІЛ). 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 мРНК вакцина проти ВІЛ.
Encouraged by the results, the phase 1 клінічний trial (NCT05217641) has been sponsored by National Institute of Allergy and Infectious Diseases (NIAID), which is currently recruiting participants.
Інший клінічний trial (NCT05001373) sponsored by International AIDS Vaccine Initiative (IAVI) based on Moderna’s мРНК 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 клінічний випробування, МРНК-вакцини проти ВІЛ/СНІДу можуть стати доступними найближчим часом.
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Список використаної літератури:
- Zhang, P., Narayanan, E., Liu, Q. et al. A multiclade env–gag VLP мРНК vaccine elicits tier-2 ВІЛ-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, ВІЛ-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 мРНК 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 (мРНК-1644) and Core-g28v2 60mer mRNA Vaccine (мРНК-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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