HJBR Jan/Feb 2021

HEALTHCARE JOURNAL OF BATON ROUGE I  JAN / FEB 2021 29 ferritin-based MERS-CoV S protein, adju- vanted with MF59, promoted multiple an- tibody responses, including high levels of IgA antibody titers that resulted in potent mucosal immune responses (58). A study by Tang et al. has indicated that there are no significant differences in the neutraliz- ing activity of the serum derived frommice 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 and it may continue to circulate through the population like the common cold viruses do now. Once recovered from COVID-19, how long do you believe immunity lasts? Do you recommend vaccines for this group? JAMES MCLACHLAN: This is a great ques- tion and one that we do not entirely know the answer to at this point. This is mostly due to the fact that the virus has only been cir- culating in the population for about a year, meaning that the longest we can determine immunity would be a year. Making this ob- servation was hampered by the fact that we didn’t really have the laboratory capacity and reagents to start looking at lasting immunity until the spring of this year. That said, a few studies have started to look at this carefully and have found that the two major types of immunity, that mediated by the cells that make antibodies (B cells) and immunity caused by specialized cells called T helper cells (that literally help the rest of the immune system perform better), are able to recall the virus even eight months later when those cells are harvested from people who were in- fected. This was true for 90% of the patients that had recovered from the virus, while 10% of recovered patients showed no signs of im- munity to infection. It is not entirely clear how long lasting or potent immunity will be for the very long term, but for most other viral infec- tions, immunity can last for years. Indeed, most encouraging for this is that the immune response to this virus seems to behave com- parably to other, similar viruses, indicating that immunity will last a long time. A caveat to this is that it is not clear how severity of infection induces immunity – do more severe cases develop more robust immune respons- es, or is the immunity less vigorous? Most of the patients that have been thus far studied have shown predominantly mild or no symp- toms of disease. We would recommend any person, exposed or otherwise, receive a full course of vaccines. First off, it is impossible to know whether you might fall in the 10% of people who showed no immune response to infection, and second, a vaccine would almost certainly act as a booster for the ex- isting anti-viral immunity caused by the initial infection, further strengthening the immune response and inducing the most durable pro- tection for the long term. Lastly, the vaccine will induce consistent immunity across almost all populations and is the most likely to en- able the achievement of herd immunity in the absence of increased fatalities. Are you personally taking the first- generation vaccine when offered? MORICI: Yes, we will both absolutely take any first-generation vaccine once it is autho- rized or approved by the FDA as soon as it’s available. Some top-level healthcare poli- cymakers believe children should be last on the list to get COVID-19 vaccines, because they currently have lower death rates than other groups, and the long-term vaccine side-effects are simply unknown. Do you recommend, at this point, children, as a group, be vaccinated with first generation of vaccines, if available? MORICI: The FDA will likely follow the rec- ommendations of an appointed vaccine ad- visory committee composed of independent scientists and clinicians who will review the safety, immunogenicity and efficacy data gathered from the clinical trials. Currently, the front-runner vaccines that are likely to be approved or authorized in the next month or two have not been evaluated in individuals less than 18 years of age, although additional trials are anticipated that will enroll children 12 and older. The advisory committee is un-