Heralding a new approach to challenging infections, cancer…

January 5, 2021 0 By S Harachand

mRNA vaccines are touted to be a promising alternative to conventional vaccine approaches. These vaccines have high potency, capacity for rapid development and potential for low-cost manufacture and safe administration.

The mRNA vaccine field is developing rapidly. A large body of preclinical data has accumulated over the past several years, and multiple human clinical trials have demonstrated that mRNA vaccine platforms could be effectively used against certain infectious diseases where conventional vaccine approaches have largely failed to produce effective vaccines against viruses such as HIV-1, herpes simplex virus and respiratory syncytial virus (RSV) that cause chronic or repeated infections and several types of cancer.

These vaccines induce strong CD8+ T cell responses in addition to potent CD4+ T cell responses. This may be due to the efficient presentation of endogenously produced antigens on major histocompatibility complex (MHC) class I molecules.

Additionally, mRNA vaccines show the ability to generate robust neutralising antibody responses in animals with only one or two low-dose immunisations, unlike DNA immunization. Studies found that mRNA vaccines have elicited protective immunity against a variety of infectious agents in animal models.

Amplifying and Non-replicating RNAs

Broadly, two categories of RNA vaccines have been utilised against infectious pathogens: self-amplifying or replicon RNA vaccines and non-replicating mRNA vaccines.

Self-amplifying RNA viral vectors have elicited strong cellular and humoral immune responses in animal models.

Clinical trials have demonstrated safe application of RNA viral vectors. Its use was found promising in rhabdovirus-based phase III trials on an Ebola virus vaccine. Preclinical and clinical applications of self-amplifying RNA viral vectors have proven efficient enough for vaccine development and due to the presence of RNA replicons, amplification of RNA in host cells will generate superior immune responses with significantly reduced amounts of RNA delivered, studies show.

The delivery methods characterise non-replicating mRNA vaccines. They can be administered either through ex vivo loading of dendritic cells or by direct in vivo injection into a variety of anatomical sites.

Cancer researchers pursue dendritic cell mRNA vaccines to generate cell-mediated immunity. This approach is not heavily pursued for infectious diseases except for HIV-1, currently.

Non-replicating mRNA vaccines are directly injectable, simple and economical.

Nucleoside-modified vaccines

Nucleoside-modified mRNA vaccines are a new and more efficacious category of mRNA vaccines.

A single intradermal injection of lipid nanoparticle (LNP)-formulated mRNA encoding Zika virus prM-E, modified with 1-methylpseudouridine and FPLC purification, elicited protective immune responses in mice and with the use of as little as 50 μg (0.02 mg kg−1) of the vaccine in macaques.

A recent study evaluated the immunogenicity of LNP-complexed, nucleoside-modified, non-FPLC-purified mRNA vaccines against influenza HA 10 neuraminidase 8 (H10N8) and H7N9 influenza viruses for the first time, in humans.

The mRNA vaccine encoding H10N8 HA is currently undergoing clinical testing (NCT03076385).

mRNA vaccines have demonstrated viability to combat cancer in several preclinical and clinical studies.