HJAR Jan/Feb 2021

HEALTHCARE JOURNAL OF ARKANSAS 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 Baptist Health Center for Clinical Re- search in Arkansas is one of the first sites in the U.S. to study a novel COVID prevention agent, using two monoclonal antibodies in- stead of a vaccine. “This monoclonal anti- body could be an alternative to a COVID-19 vaccine or could be complementary since we hope the monoclonal antibodies confer immunity almost immediately whereas vac- cines take several weeks,” says Richard G. Pellegrino, MD, PhD, CEO and President of Baptist Health Center for Clinical Research. “There will be around 100 sites total. How- ever, we were amongst the first to open for enrollment. The order of opening sites is determined by the capability. The most important thing, was our ability to combine the speed and service of a privately owned research site with the resources of an inte- grated medical system.” Baptist Health Center for Clinical Re- search’s study coincides with a broader nationwide effort, Operation Warp Speed, which was announced in May as a public- private partnership to facilitate, at an un- precedented pace, the development, man- ufacturing and distribution of COVID-19 measures including vaccines, diagnostics and treatments. “The study lasts for one year,” Pellegrino said, “however, as with the vaccine studies, there is an indepen- dent safety board that looks at the data at Baptist Health Center for Clinical Research Among First Sites in U.S. to Study Novel COVID Prevention Agent predetermined in- tervals. If it is over- whelmingly positive and appears safe, the company [As- traZeneca] can ap- ply for emergency use approval and the monoclonal an- tibody may become available earlier. In any case, the study would continue. Pellegrino’s trial is not a vaccine or an ad- juvant, which are only used with vaccines; in- stead, the antibodies bind to the SARS-Cov2 spike protein and prevent it from replicating and thereby prevent disease. “Subjects will not be exposed to COVID-19,” he contin- ued, “67% of participants will receive an in- tramuscular injection of the antibodies, 33% will receive placebo. They will then compare the number of people in each group who contract COVID-19 naturally, hoping that less people in the treated group will con- tract COVID-19.” More Information including how to par- ticipate is available at arkansascovidvaccine. com. Participants will be compensated for time and travel if they qualify and enroll in the study. Study-related care is provided at no cost and health insurance is not required nor needed. n by Philip Gatto