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-клиничен 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 клиничен 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
Изминаха повече от 40 години от първия доклад за ХИВ/случай на СПИН през 1981 г. Въпреки дългите съгласувани усилия на научната и медицинска общност по целия свят, безопасна и ефективна ваксина срещу ХИВ/СПИН досега не е била възможна поради няколко предизвикателства, включително забележителната антигенна променливост на протеина на обвивката (Env), защитената конфигурация на запазени епитопи и автореактивност на антителата. Бяха изпробвани няколко подхода, но резултатите бяха незадоволителни. Само едно изпитване при хора може да предложи ниско ниво на защита (~30%).
Успехът на иРНК vaccines against SARS CoV-2 has opened up the possibility of developing mRNA technology-based vaccines for other pathogenic viruses like Human Immunodeficiency viruses (ХИВ) responsible for AIDS. The researchers of NIH’s National Institute of Allergy and Infectious Diseases (NIAID) have recently reported development of a novel mRNA ХИВ vaccine which has shown promises in preclinical trials on animals.
The NIAID research team used mRNA for expression of two viral proteins – ХИВ-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. Антитела were formed that could neutralise and reduce the risk of infection (VLPs could not cause infection because of lack of genome of ХИВ). 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 ХИВ.
Encouraged by the results, the phase 1 клиничен trial (NCT05217641) has been sponsored by National Institute of Allergy and Infectious Diseases (NIAID), which is currently recruiting participants.
Друг клиничен 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 клиничен изпитания, тРНК ваксини срещу ХИВ/СПИН може да се появи в близко бъдеще.
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Литература:
- Zhang, P., Narayanan, E., Liu, Q. et al. A multiclade env–gag VLP mRNA vaccine elicits tier-2 ХИВ-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, ХИВ-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 и Moderna стартират изпитание на антигени за ваксина срещу ХИВ, доставени чрез тРНК технология. Публикувано на 27 януари 2022 г. Налично на https://www.iavi.org/news-resources/press-releases/2022/iavi-and-moderna-launch-trial-of-mrna-hiv-vaccine-antigens
- Проучване от фаза 1 за оценка на безопасността и имуногенността на eOD-GT8 60mer mRNA ваксина (mRNA-1644) и Core-g28v2 60mer mRNA ваксина (mRNA-1644v2-Core). ClinicalTrials.gov Идентификатор: NCT05001373. Спонсор: Международна инициатива за ваксини срещу СПИН. Наличен в https://clinicaltrials.gov/ct2/show/NCT05001373?cond=NCT05001373&draw=2&rank=1
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