A trump card to combat future pandemics

A new advancement in vaccine development has clued the world to intelligently cope with the next pandemic.

By Khola Zafar

Almost a year back, Moderna and Pfizer-BioNTech vaccines against corona virus had benchmarked the vast immunization throughout the world. With a great number of world population immunized against current COVID-19 pandemic, the debut of new Arcturus vaccine is a bit late. Arcturus vaccine is a self-amplifying messenger RNA (saRNA) vaccine that carries the instructions for its own replication once inside the host cell. The vaccine has a notable significance of low cost, smaller dose requirement and more convenient storage. Despite the fact of its late release, the saRNA vaccine introduced by Arcturus Therapeutics, a San Diego-based biotech company, has proved its worth against COVID-19. Chivukula, the company’s chief scientific officer is therefore optimistic, that its low cost will help find its way through the market in less vaccinated countries.

Those initially developed Pfizer and Moderna vaccines comprises a piece of mRNA as an antigen encoding corona virus spike protein. mRNA in these vaccines instruct the cellular machinery to make viral proteins and to lead the host’s immune system to generate an immune response upon the exposure of actual pathogen. Whereas self-amplifying mRNA vaccine is a step forward from conventional RNA vaccines. Along with the antigenic proteins these vaccines also include viral replication machinery that encodes four extra enzymes from alpha viruses to self-amplify in human body. This self-replication process ultimately allow the vaccine to last longer in one’s body as even after the generation of body’s immune response to eliminate the antigen, cell has the blueprint to make more non-infectious antigens.

 

Is Arcturus candidate really protective against Covid-19?

A study conducted by Arcturus Therapeutics in Vietnam has reported that the protection level of Arcturus’s “self-amplifying” mRNA vaccine is 55% against symptomatic COVID-19 infection and is 95% efficacious against serious infection and death. The 55% efficacy of the Arcturus’s product against symptomatic infection of Covid 19 is not so great compared to other two companies’ with the protection level of 90-95% in their trials. This lower efficacy can be justified by the fact that the first two vaccines were derived and tested against the original               SARS-CoV-2 virus only. The Arcturus vaccine derived from the spike protein sequence of original SARS-CoV-2 virus on the other hand had to face the dramatically evolved more virulent Delta and Omicron variants, circulating in the test population at that time. Thus, a Vaccinologist Deborah Fuller of the University of Washington School of Medicine states that “It’s a huge accomplishment that for the first time a self-amplifying RNA vaccine has been shown to be safe and effective,”.

 

Potential of Arcturus’s self-amplifying RNA vaccines

The dose requirement for self-amplifying vaccines is lower to achieve a comparatively equal level of effectiveness as proven in clinical trials. In a trial, 5 grams of self-amplifying mRNA was given in two shots spaced by 28 days, whereas, for the first two shots, the Pfizer-BioNTech and Moderna vaccines use 30-microgram and 100-microgram dosages, respectively. Results of these clinical trials suggested that much smaller doses of saRNA can be as effective as mRNA based conventional vaccines. Thus in an emergency situation say, for example, a pandemic, a smaller dose requirement to immunize the world is significant as it allows more individuals to be vaccinated rapidly and at a cheaper cost. Self-amplifying ability of these Arcturus vaccines is itself a trump card as these vaccines last longer in the body than traditional mRNA vaccines, the exposure time of immune system to vaccine is therefore longer, leading to better memory generation against antigen. Arcturus practice to lyophilize its vaccines eliminates the requirement of cold-chain maintenance. As the powdered vaccine formulation can easily be stored at room temperature. This convenient storage may not be possible for liquid formulation of other mRNA vaccines by Pfizer-BioNTech and Moderna. Along with all other efficacies, efficient delivery routes are also critical for the success of any vaccine. Arcturus vaccines are therefore packaged in lipid nanoparticles (LNP) for their promising delivery.

Arcturus Therapeutics suggests that the self-amplifying mRNA vaccine technology can be broadened against a variety of different viruses. Also that its low dose requirement is a good way to combine different viral antigens in a single shot. Built on the overall marked out primacy of self-amplifying mRNA vaccine we can anticipate that this saRNA vaccine could certainly be a promising technology to equip the world against a future pandemic.