HJBR Jan/Feb 2021

HEALTHCARE JOURNAL OF BATON ROUGE I  JAN / FEB 2021 25 vaccine also indicated that immunization with whole inactivated virus could lead to vaccine-associated enhanced respira- tory disease (VAERD), manifested by al- lergic inflammation and Th2 type immune responses (38). Altogether, these studies suggest that vaccines formulated with var- ious antigen isotypes may require proper adjuvant selection to achieve the desired immune protection. In this paper, we re- viewed adjuvants that have already been incorporated in the coronavirus vaccines under exploratory and pre-clinical investi- gations. By reviewing the vaccine formula- tions and the types of immune responses that were induced, we provide information that will enable proper adjuvant selection for COVID-19 vaccines to facilitate rapid vaccine delivery. Aluminum Salt-Based Adjuvants Aluminum salt-based adjuvants (alum) were the first adjuvants used in licensed human vaccines. They are still the most widely used because of their wide-spec- trum ability to strengthen immune re- sponses and their excellent track record of safety (39–41). In limited coronavirus vac- cine studies, it has been suggested that neu- tralizing antibody against the spike protein might be mechanistically correlated with immune protection (42). When alum was formulated with S protein or receptor- binding domain (RBD), it significantly en- hanced humoral immune responses. This was demonstrated by higher titers of serum IgG1, increased high affinity viral neutraliz- ing antibodies, and the generation of long- lasting memory B cells in mice (13, 17–19). Additionally, Alum was formulated with the inactivated and VLP vaccines contain- ing E, M, and N proteins (11, 12, 14) (Table 1) that showed enhanced IgG1 and neutral- izing antibody titers (14) and prolonged durability (12). Studies also demonstrated that alum adjuvant plays an essential role in the dose-sparing of CoV vaccines. In a SARS S protein subunit vaccine, the alum- adjuvanted S protein (1 μg) group showed neutralizing antibody titers similar to or higher than the non-adjuvanted S protein (50 μg) group. The alum-adjuvanted S protein (5 μg) group showed a geometric mean titer (GMT) twice as high as the non- adjuvanted S protein (50 μg) group (20). It should also be noted that different types of alumwere selected in the studies, including Alhydrogel, which is chemically crystalline 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