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-clinico 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 clinico 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
Sono trascorsi più di 40 anni dal primo rapporto di HIV/AIDS nel 1981. Nonostante i lunghi sforzi concertati della comunità scientifica e medica mondiale, un vaccino sicuro ed efficace contro l'HIV/AIDS non è stato finora possibile a causa di diverse sfide tra cui la notevole variabilità antigenica della proteina dell'involucro (Env), il configurazione degli epitopi conservati e autoreattività degli anticorpi. Sono stati provati diversi approcci, tuttavia i risultati sono stati insoddisfacenti. Solo una sperimentazione umana potrebbe offrire un basso livello di protezione (~30%).
Successo di 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) responsabile dell'AIDS. I ricercatori del National Institute of Allergy and Infectious Diseases (NIAID) del NIH hanno recentemente segnalato lo sviluppo di un nuovo mRNA HIV vaccino che ha mostrato promesse preclinico sperimentazioni sugli animali.
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. Anticorpi si formarono cellule che potevano neutralizzare e ridurre il rischio di infezione (le VLP non potevano causare infezioni a causa della mancanza del genoma di 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 vaccino contro HIV.
Incoraggiati dai risultati, la fase 1 clinico (NCT05217641) è stato sponsorizzato dal National Institute of Allergy and Infectious Diseases (NIAID), che sta attualmente reclutando partecipanti.
Un altro clinico 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’’.
A seconda dei risultati soddisfacenti di sicurezza ed efficacia del clinico prove, Vaccini a mRNA contro l’HIV/AIDS potrebbero diventare disponibili nel prossimo futuro.
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Riferimenti:
- Zhang, P., Narayanan, E., Liu, Q. et al. A multiclade env–gag VLP mRNA vaccine elicits tier-2 HIV-1-anticorpi neutralizzanti e riduce il rischio di infezione eterologa da SHIV nei macachi. Nat Med 27, 2234–2245 (2021). https://doi.org/10.1038/s41591-021-01574-5
- Uno studio clinico per valutare la sicurezza e l'immunogenicità dei vaccini mRNA del trimero HIV BG505 MD39.3, BG505 MD39.3 gp151 e BG505 MD39.3 gp151 CD4KO HIV Trimero in soggetti sani, HIV-Partecipanti adulti non infetti – Identificativo ClinicalTrials.gov: NCT05217641 Sponsor: Istituto nazionale per le allergie e le malattie infettive (NIAID). Disponibile a 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 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-1644) and Core-g28v2 60mer mRNA Vaccine (mRNA-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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