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-klinisk 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 klinisk 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
Det er mer enn 40 år siden den første rapporten av HIV/AIDS-saken i 1981. Til tross for lang samordnet innsats fra det vitenskapelige og medisinske miljøet over hele verden, har en sikker og effektiv vaksine mot HIV/AIDS ikke vært mulig så langt på grunn av flere utfordringer, inkludert bemerkelsesverdig antigene variabilitet av envelope protein (Env), den beskyttede konfigurasjon av konserverte epitoper og autoreaktivitet av antistoffer. Flere tilnærminger ble prøvd, men resultatene var utilfredsstillende. Bare ett menneskelig forsøk kunne tilby et lavt beskyttelsesnivå (~30 %).
Suksess av 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) responsible for AIDS. The researchers of NIH’s National Institute of Allergy and Infectious Diseases (NIAID) have recently reported development of a novel mRNA HIV vaccine which has shown promises in preklinisk trials on animals.
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. antistoffer were formed that could neutralise and reduce the risk of infection (VLPs could not cause infection because of lack of genome of 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 vaccine against HIV.
Encouraged by the results, the phase 1 klinisk trial (NCT05217641) has been sponsored by National Institute of Allergy and Infectious Diseases (NIAID), which is currently recruiting participants.
En annen klinisk 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 klinisk prøvelser, mRNA vaksiner mot HIV/AIDS kan bli tilgjengelig i nær fremtid.
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Referanser:
- Zhang, P., Narayanan, E., Liu, Q. et al. A multiclade env–gag VLP mRNA vaccine elicits tier-2 HIV-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, HIV-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 – Pressemeldinger – IAVI og Moderna lanserer forsøk med HIV-vaksineantigener levert gjennom mRNA-teknologi. Lagt ut 27. januar 2022. Tilgjengelig på https://www.iavi.org/news-resources/press-releases/2022/iavi-and-moderna-launch-trial-of-mrna-hiv-vaccine-antigens
- En fase 1-studie for å evaluere sikkerheten og immunogenisiteten til eOD-GT8 60mer mRNA-vaksine (mRNA-1644) og Core-g28v2 60mer mRNA-vaksine (mRNA-1644v2-Core). ClinicalTrials.gov Identifikator: NCT05001373. Sponsor: International AIDS Vaccine Initiative. Tilgjengelig i https://clinicaltrials.gov/ct2/show/NCT05001373?cond=NCT05001373&draw=2&rank=1
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