HIV-1 mRNA Vaccines
AIDS is a chronic and life-threatening condition, caused by the infection of human immunodeficiency virus (HIV). Nowadays, control of the AIDS epidemic is one of the leading global health priorities. To prevent HIV transmission, clinical progression, and death, the development of HIV vaccines is a major priority. HIV vaccination has undergone periods of significant growth. With the progress in mRNA technologies, the mRNA-based vaccine strategy has shown a particular promise. This emerging vaccine platform shows enormous flexibility and room for optimization, owning to their better safety profile, ample possibilities of design mRNA backbone, various delivery systems, as well as easy manufacture.
HIV-1
Despite the great progress in understanding the biology of HIV-1 infection, there is no licensed HIV vaccine on the market. Human immunodeficiency virus type 1 (HIV-1) is one of the most difficult vaccine targets and has several strategies to escape protective immune responses. The virus has the ability to hide neutralization epitopes due to the large number of host glycans linked with the HIV-1 envelope (Env). HIV Env is the only surface glycoprotein target for broadly neutralizing antibodies (bnAbs). Besides, HIV Env has rapid mutability, thus host anti-HIV antibodies do not evolve fast enough to effectively fight the virus. Fortunately, bnAbs can be observed in some HIV-infected individuals several years after natural infection, suggesting that it is possible to develop antibody-based protective vaccines. There is enormous effort in the development of effective HIV vaccines. However, most types of vaccines elicit some level of neutralizing antibodies against tier 1 viruses and these antibodies cannot protect against HIV infection. As an ideal antibody-driven HIV vaccine, it should elicit long-lived antibody responses, which can neutralize multiple tier 2 viruses.
mRNA-based HIV vaccines
There are several preclinical and clinical studies of mRNA-based vaccines for the treatment of HIV. One study is based on mRNA-expressed antibody engineering and has demonstrated nucleoside-modified, LNP-encapsulated mRNA encoding the broadly neutralizing antibody to protect humanized mice against HIV infection. The same team also showed the feasibility of antibody-based protective vaccines against HIV. LNP-encapsulated mRNA vaccines had the ability to elicit high levels of antibodies in rabbits and non-human primates and efficiently activate T follicular helper (Tfh) cells, which can lead to neutralizing antibody responses. Besides, the self-amplifying mRNA vaccine shows the promise against HIV. A study based on self-amplifying mRNA vaccine and highly conserved regions of the HIV-1 proteome, has demonstrated a relatively strong immune response against HIV.
In addition to the directly injectable, formulated HIV mRNA vaccines in models, there are a small number of studies using an ex vivo approach to target HIV. Human autologous dendritic cells (DCs) are electroporated with mRNAs encoding HIV antigens, followed by reinfused into the patients. However, this approach is labor-intensive, expensive, and low efficiency (only induce moderate T cell activation). In recent years, in vivo DC targeting strategy, intranodal administration of naked mRNAs encoding critical HIV-1 target epitopes from Vif, Gag, Pol, and Nef as well as a combination of immunostimulatory molecules, is applied to overcome the technical difficulties of ex vivo DC treatment. And similar to ex vivo DC treatment, this in vivo regimen elicits moderate antigen-specific T cell responses in mice and humans.
Creative Biogene provides a range of customized and inventive solutions, involving the development of influenza mRNA vaccines, anti-parasite mRNA vaccines, mRNA vaccines against HIV as well as the global SARS-CoV-2 pandemic. We are committed to exerting the potential of synthetic mRNA as an important vaccine candidate for infectious diseases, hoping to meet our customers' specific requirements for projects at the preclinical stages. If you are interested in this area, please feel free to contact us. We look forward to providing services for your next project.
Reference
- Alameh, M. G. (2020). "Messenger RNA-Based Vaccines Against Infectious Diseases."
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