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 moléculas de ARN 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-por trial in animals. The novel ARNm-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 por trial sponsored by NIAID has started. Another clinical trial sponsored by International AIDS Vaccine Initiative (IAVI) based on Moderna’s ARNm platform based is evaluating HIV vaccine antigens
Han pasado más de 40 años desde el primer reporte de VIH/SIDA en 1981. A pesar de los esfuerzos concertados de la comunidad científica y médica de todo el mundo, hasta ahora no ha sido posible una vacuna segura y eficaz contra el VIH/SIDA debido a varios desafíos, incluida la notable variabilidad antigénica de la proteína de la envoltura (Env), la proteína protegida configuración de epítopos conservados y autorreactividad de anticuerpos. Se probaron varios enfoques, sin embargo, los resultados no fueron satisfactorios. Solo un ensayo en humanos podría ofrecer un bajo nivel de protección (~30%).
Éxito de ARNm vaccines against SARS CoV-2 has opened up the possibility of developing ARNm technology-based vaccines for other pathogenic viruses like Human Immunodeficiency viruses (VIH) responsible for AIDS. The researchers of NIH’s National Institute of Allergy and Infectious Diseases (NIAID) have recently reported development of a novel mRNA VIH vaccine which has shown promises in preclínico trials on animals.
The NIAID research team used ARNm for expression of two viral proteins – VIH-1 envelope (Env) protein and simian immunodeficiency virus (SIV) Gag protein. Injection of ARNm 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. Anticuerpos were formed that could neutralise and reduce the risk of infection (VLPs could not cause infection because of lack of genome of VIH). 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 ARNm vacuna contra VIH.
Encouraged by the results, the phase 1 por trial (NCT05217641) has been sponsored by National Institute of Allergy and Infectious Diseases (NIAID), which is currently recruiting participants.
Otra por trial (NCT05001373) sponsored by International AIDS Vaccine Initiative (IAVI) based on Moderna’s ARNm 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 por juicios, Vacunas de ARNm contra el VIH/SIDA podría estar disponible en un futuro próximo.
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Referencias:
- Zhang, P., Narayanan, E., Liu, Q. et al. A multiclade env–gag VLP ARNm vaccine elicits tier-2 VIH-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, VIH-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 ARNm 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 (ARNm-1644) and Core-g28v2 60mer mRNA Vaccine (ARNm-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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