HJAR Jan/Feb 2021

30 JAN / FEB 2021  I  HEALTHCARE JOURNAL OF ARKANSAS COVID-19 VACCINE 2.0 potent mucosal vaccine adjuvant that in- ducesTh1 andTh17 cytokines in a plant-de- rived H5 influenza vaccine after intranasal vaccination (75). In a very recent study, it was demonstrated that pulmonary surfac- tant–biomimetic liposomes encapsulating STING agonists could be used as mucosal adjuvants for universal influenza vaccines that trigger rapid humoral and cellular immune responses and exhibit sustained cross-protection against influenza (76). Though cdGMP in polymeric nanoparticle formulations has been used as adjuvants with MERS-CoV S-RBD protein, its abil- ity to induce mucosal immunity was not specifically examined (72). Thus, further studies are warranted to examine both the efficacy and safety of mucosal adjuvants in coronavirus vaccines. Conclusion and Perspectives In this article, we provided an overview of previously studied adjuvants in candi- date inactivated and subunit coronavirus vaccines with a focus on the types of adju- vants in the vaccine formulations and the nature of immune responses to the formu- lated vaccines. These previous studies pro- vided a convenient basis for the screening of adjuvants required to develop coronavi- rus vaccines. In-depth reviews of the vari- ous adjuvants, a comprehensive under- standing of their impacts on the extent and types of immune responses, and an explo- ration of their combinations with various antigen types and vaccine platforms will facilitate the selection of adjuvants that provide the required immunological pro- tection of coronavirus vaccines. In the absence of a cure for COVID-19, effective and safe vaccines are urgently re- quired. Adjuvants such as aluminum-based salts, TLR agonists, emulsions, and other novel adjuvants have distinctive physico- chemical properties, which can be signifi- cant in regulating the strength, duration, and types of immune responses (19, 63, 77). Studies have suggested that neutralizing antibodies are critical for immune protec- tion (34, 42).While mechanistic studies are still being conducted, emerging evidence has suggested that SARS-CoV-2-specific CD4+ and CD8+ T cells in coordination with neutralizing antibodies are required for generating protective immunity against SARS-CoV-2 (33). Thus, the appropriate adjuvants should be selected to formulate specific antigens that will achieve optimal tirely possible that SARS CoV-2 will eventu- ally lose its virulence over time, similar to the coronaviruses that cause the common cold, 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