HJBR Jan/Feb 2021

28 JAN / FEB 2021  I  HEALTHCARE JOURNAL OF BATON ROUGE COVID-19 VACCINE 2.0 enhanced respiratory disease (VAERD) (38, 48), however, there are no evidences that alum-adjuvanted CoV vaccines show the effect. When alum was used as an adjuvant in CoV vaccines (Table 1), there was a lack of Th1 CD4+ T cell and cytotoxic CD8+ T cell immune responses, which is typical for alum-adjuvanted vaccines (49). However, recent study has demonstrated that the SARS-CoV-2–specific adaptive immune re- sponse correlated with milder disease, in- dicating that coordinated CD4+ and CD8+ T cell responses play a synergistic effect in the protective immunity of COVID-19 (33). Several other adjuvants, which are capable of inducing more balanced Th1/Th2 or Th1-biased immune responses, have been formulated in CoV vaccines and will be dis- cussed in the following sections. Emulsion Adjuvants The emulsion adjuvants, MF59, and AS03 have already been used in licensed human vaccines to improve the immuno- genicity of the antigens (50, 51). Compared with alum that lacks the capability to medi- ate cell-mediated immunity (49), MF59 and AS03 can elicit more balanced immunity, possibly by improving antigen uptake, re- cruiting immune cells, and promoting the migration of activated antigen-presenting cells (28, 50, 52). Emulsion adjuvants have already been used in preclinical studies of vaccines against coronavirus. MF59 used in inactivated SARS and MERS vaccines, as well as vaccines containing the RBD do- main of the MERS-CoV spike (S) protein, has exhibited excellent adjuvanticity, with potent humoral immune responses, i.e., high titers of neutralizing antibodies, and cell-mediated immunity in the coronavi- rus vaccines (53–55). In addition, depend- ing on the types of antigen, cell-mediated immunity induced by MF59 differs. When formulated with the MERS-CoV S protein, MF59 enhanced both effective CD4+ and CD8+ T-cell immune responses. In com- parison, when combined with inactivated SARS CoV, MF59 induced significant CD4+ T cell, but not CD8+ T cell responses (56, 57). However, in another study by Zhang et al., it was demonstrated that when MERS S protein was adjuvanted with MF59, it induced higher IgG1 and IgG2a antibod- ies with a slightly Th2-biased response (54). Subsequent studies also showed that the top of the list). Should the pub- lic and practitioners feel comfort- able injecting this first generation of “rushed” COVID-19 vaccines into so many as is being suggested? MORICI: The vaccine advisory committee and FDA will analyze the raw data accumu- lated from the initiation of phase 1 to the ongoing phase 3 clinical trials that enrolled between 30,000-44,000 participants. The data includes at least two months of follow- up after administration of the second vaccine dose in at least half of the phase 3 trial partic- ipants. As of now, there have been no serious adverse events associated with the vaccines. Notably, as stated previously, the mRNA vac- cine technology used in these vaccines has already been in human clinical trials in vari- ous forms prior to this one, albeit at a smaller scale. This should provide even greater con- fidence that these vaccines are safe over the longer term. While it is certainly a possibility that rare serious adverse events will only be identified once hundreds of millions of doses have been administered, the impact of the pandemic and the risks associated with SARS CoV-2 infection far outweigh the risks of the vaccines. Congratulations to your team on be- ing awarded a Fast Grant to develop bacteria-based adjuvants for the next-generation COVID-19 vaccine, 2.0, if you will. Will you please tell us about what you are working on and why it is important? MCLACHLAN: As mentioned above, the first generation of vaccines are extremely promising but may not be able to prevent as- ymptomatic transmission or may not be able to target the immune response to the portal of viral entry (in this case, the lung). Most vaccines include a component called an ad- juvant that essentially alerts the immune sys- tem to respond to the vaccine, which it might otherwise ignore. There are a variety of adju- vants currently approved for vaccines; how- ever, not all of these adjuvants are capable of eliciting the most complete of robust im- mune response. We have developed and uti- lized a new generation of adjuvants that we have found in our research to be capable of activating all parts of the immune response. More importantly, we have found that our adjuvants can target the appropriate immune response to the mucosal tissues such as the lung. Our Fast Grant proposes to test these new adjuvants in the next generation of CO- VID-19 vaccines to induce, long-term lung immunity against the virus. This would ulti- mately allow us to prevent both disease and transmission in people exposed to the virus as we go forward. Is SARS-Cov-2 evolving (like the flu)? MORICI: The introduction of SARS CoV-2 into the human population is a recent event, and mutations do appear to be accumulating as the virus spreads more widely among the human population. So far, these mutations do not appear to be altering its proteins in such a way that they would circumvent the current vaccines. This is in contrast to Influenza (flu) virus that exhibits both antigenic drift (minor changes in its surface proteins) and antigenic shift (major changes in composition) that forces us to modify the vaccine each year to match the most common flu strains circulat- ing in the population. Because SARS CoV-2 and the flu virus are so different, it is not really fair to compare the two in this way. While the type of genetic material inside of each is simi- lar (RNA), the way this material is arranged is very different, and this arrangement leads to flu acquiring far more, and more dangerous, mutations compared to SARS CoV-2. It is en- tirely possible that SARS CoV-2 will eventu- ally lose its virulence over time, similar to the coronaviruses that cause the common cold,