Astrazeneca Covid Vaccine Formulation

The decision to combine the results of two different dosages has been criticized by some who have questioned why the results were combined. [104] [105] [106] AstraZeneca responded to the criticism by agreeing to conduct a new country study at the lowest dose, which led to the 90% claim. [107] To boost adaptive immunity, a vaccine requires a pathogen-specific immune gene as well as an adjuvant – the latter stimulates the innate immune system and provides the second signal needed for T cell activation. An optimal adjuvant stimulates innate immunity without triggering systemic inflammation that could cause serious side effects. For mRNA vaccines, mRNA can serve as both an immune gene (encoding the viral protein) and an adjuvant due to the intrinsic immunostimulating properties of RNA. Upon entry into cells, single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA) are detected by various endosomal and cytosolic innate sensors that are an essential part of the innate immune response to viruses. Toll-like endosomal receptors (TLR3 and TLR7) bind to dRNA in the endosome, while inflammasome components such as MDA5, RIG-I, NOD2 and PKR bind to ndRA and nRNA in the cytosol, resulting in cell activation and production of type I interferon and multiple inflammatory mediators7 (Fig. 1). Current vaccines contain single-stranded mRNA purified and transcribed in vitro with nucleotides modified to reduce binding to TLR and immune sensors, thereby limiting the excessive production of type I interferon and its inhibitory function in cell translation (see Ref.7). The LNP carrier further protects mRNA, can target administration to lymphatic vessels, and promote protein translation into lymph nodes (LN)7. Once in the LN, the LNP is devoured by dendritic cells (DC), which then produce the antigen and present T cells to activate the adaptive immune response. Preclinical and early results from human studies show that both vaccines produce anti-protein S IgG and virus-specific neutralizing antibody responses several months after vaccination5,6, while T-cell data have not yet been fully elucidated.

This short-term shelf life is likely sufficient to contain the spread of SARS-CoV-2 and pave the way for a return to normalcy. However, the global spread of SARS-CoV-2 as well as the advent of S-protein variants could potentially limit the effectiveness of the vaccine. Eradicating SARS-CoV-2 from the population can be difficult due to reservoirs in unvaccinated individuals and/or other animal species. New vaccine formulations containing S-variant sequences and additional SARS-CoV-2 proteins could be produced, and annual or semi-annual SARS-CoV-2 vaccines could be administered to persistent strains and/or seasonal variants. The mRNA vaccine formulation is ideal for repeated or modified vaccinations, as various mRNA containing mutant S proteins can be rapidly synthesized and incorporated into the LNP carrier. .