HJAR Jan/Feb 2021
HEALTHCARE JOURNAL OF ARKANSAS I JAN / FEB 2021 27 immunized with MERS S377-588 at 1, 5, and 20 μg in the presence of MF59, suggesting the dose-sparing effect of MF59 when it was formulated with MERS S protein (57). However, an immunopathologic lung reac- tion, as well as an increase in IL-5 and IL-13 cytokines, was seen in animal studies using both MF59-adjuvanted and adjuvant-free inactivated MERS-CoV vaccines (53). It has shown that eosinophil infiltrations with higher Th2-type cytokine secretion aggra- vated the hypersensitivity-type pulmonary immunopathology when vaccinated with MF59-adjuvanted inactivated virus vac- cines as compared with the inactivated vi- rus vaccines alone (53). Another emulsion adjuvant, AS03, elicits both potent humoral and cellular immune responses to an inactivated whole virion SARS-CoV (WI-SARS) vaccines (59) com- pared with the virion without adjuvants. Moreover, in the presence of the AS03 ad- juvant, an identical trend toward specific CD4+ T cell responses was observed when immunized with SARS-CoV containing the equivalent of 0.5 or 1.5 μg of S protein (59). Therefore, the addition of AS03 tends to potentiate the immune responses with a lower dosage of antigen. Considering its capability to induce both arms of the im- mune system, S protein, RBD domain, and N protein can also be formulated with AS03. Currently, GSK is sharing its AS03 adjuvant with COVID-19 vaccine develop- ers globally (29). Besides MF59 and AS03, other emul- sion-based adjuvants such as Freund’s adjuvant and Montanide ISA51 have also been formulated in CoV vaccines (54). By evaluating the titers of specific serum an- tibody responses, it has been demonstrated that Freund’s adjuvant and ISA51 elicited significant Th1 antibody responses (IgG2a) with no clear Th2 responses (IgG1) (54, 59). TLR Agonists and Other Adjuvants Toll-like receptors (TLRs), a category of pattern-recognition receptors, are critical to pathogen recognition. This allows for rapid activation of innate immunity, and subsequently, effective adaptive immunity. TLR agonists have been extensively studied as vaccine adjuvants (60, 61). CpG, Poly I:C, glucopyranosyl lipid A (GLA), and resiqui- mod (R848) are agonists for TLR9, TLR3, TLR4, and TLR7/8, respectively. These ad- juvants have been evaluated in candidate What are your thoughts on the light- ing speed the international research community approached developing and bringing COVID-19 vaccines to market? LISA MORICI: The speed of development for vaccines against COVID-19 is truly re- markable and unprecedented. Until now, the fastest vaccine ever developed was the Mumps vaccine that took four years. This his- toric accomplishment against COVID-19 is partly a result of the enormous financial com- mitment from public-private partnerships as well as the tremendous scientific advances in vaccinology over the past decade, particu- larly in the plug-n-play vaccine platforms like mRNA and viral (e.g., adenovirus) vectors. For example, while the mRNA vaccines cur- Lisa A. Morici, PhD Associate Professor of Microbiology and Immunology Tulane University School of Medicine James McLachlan, PhD Associate Professor of Microbiology and Immunology Tulane University School of Medicine Q&A covid-19 vaccine
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