mRNA Vaccines

- mRNA Vaccines - A New Era in Vaccinology

mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. 

Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use. 

Recent improvements in mRNA vaccines act to increase protein translation, modulate innate and adaptive immunogenicity and improve delivery. mRNA vaccines have elicited potent immunity against infectious disease targets in animal models of influenza virus, Zika virus, rabies virus and others, especially in recent years, using lipid-encapsulated or naked forms of sequence-optimized mRNA. 

Diverse approaches to mRNA cancer vaccines, including dendritic cell vaccines and various types of directly injectable mRNA, have been employed in numerous cancer clinical trials, with some promising results showing antigen-specific T cell responses and prolonged disease-free survival in some cases.  

Therapeutic considerations and challenges include scaling up good manufacturing practice (GMP) production, establishing regulations, further documenting safety and increasing efficacy.  

Important future directions of research will be to compare and elucidate the immune pathways activated by various mRNA vaccine platforms, to improve current approaches based on these mechanisms and to initiate new clinical trials against additional disease targets.

- mRNA and The COVID-19 Vaccines

The emergence of SARS-CoV-2 with the resultant COVID-19 pandemic resulted in the need to rapidly advance vaccine development. New vaccine technologies, such as mRNA and viral-vectored vaccines, moved rapidly through the various stages of vaccine clinical trials to FDA Emergency Use Authorization within about 9 months of starting their Phase I clinical trial. Older technologies, such as protein-based vaccines, still have not completed their US Phase 3 clinical trials. 

The success of mRNA vaccines in opens the door for applying this technology to currently vaccine-preventable illnesses (e.g., influenza) and other novel vaccine development. Fundamental basic immunological and clinical questions remain about mRNA vaccine technology that will need to be addressed for this technology to usher in a new era in vaccinology.

- COV-ID 19 Vaccine Efficacy and Effectiveness

Efficacy refers to the extent to which a vaccine reduces Covid-19 cases in a trial compared to the rate in a control group. 

If a vaccine’s efficacy rate is 80% it doesn’t mean 20 out of every 100 people who get the jab will get a symptomatic case of Covid-19. Instead it means there will be 80% fewer such cases compared with the control group. So if , say, 1% of a control group of 1,000 unvaccinated people develops Covid-19 over a certain number of months, that means 10 people will get ill. With an efficacy rate of 80%, only 2 people should get sick. 

Meanwhile, effectiveness refers to how the vaccines hold up in real life, in conditions and among populations that often differ significantly from those in trials.

The Chinese COVID-19 vaccines differ from the novel approach used by Moderna and Pfizer, which deploy messenger RNA (mRNA), genetic material that gives cells the instructions for mounting defenses against the coronavirus. Meanwhile Sinopharm and Sinovac developed inactivated Covid vaccines - using a neutralized version of the corona virus to generate immunity.