The IgG1 subtype titer was the highest in each group. Delta + Alum vaccine groups produced high levels of cross-neutralization antibodies against prototype, Beta, and Gamma strain SARS-CoV-2 viruses. There was no significant decrease in neutralizing antibody levels in any vaccine group during the observation period. CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 vaccines excited Rabbit Polyclonal to KITH_HHV1C different antibody subtypes compared with unadjuvanted vaccines; the Delta + CpG vaccine group had a higher proportion of IgG2b antibodies, indicating bias towards Th1 immunity. The proportions of IgG1 and IgG2b in the Delta + MF59-like vaccine group were similar to Amelubant those of the unadjuvanted vaccine. However, the Delta + Alum vaccine group had a higher proportion of IgG1 antibodies, indicating bias towards Th2 immunity. Antigen-specific cytokine secretion CD4/8+ T cells were analyzed. In conclusion, the results of this study show differences in the immune efficacy of CpG, MF59-like, and Alum adjuvant Delta strain inactivated SARS-CoV-2 vaccines in mice, which have significant implications for the selection strategy for vaccine adjuvants. Keywords: SARS-CoV-2, inactivated vaccines, Delta, immunogenicity, adjuvants 1. Introduction Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of the disease COVID-19, was first identified in human populations in 2019 and rapidly escalated into a global pandemic. The disease manifests in Amelubant a spectrum of severity in patients, with most individuals experiencing moderate symptoms and recovering within a few weeks. However, some develop serious complications such as pneumonia or acute respiratory distress syndrome which, unfortunately, have resulted in fatalities in some instances [1,2,3]. SARS-CoV-2 is usually categorized as an enveloped single-stranded RNA virus, falling under the genus Beta coronavirus within the Coronavirus family. It produces four structural proteins: nucleocapsid (N), glycoprotein (S), membrane (M), and envelope (E) proteins [4,5]. The S protein is composed of two subunits, S1 and S2. The receptor-binding domain name (RBD) situated around the S1 subunits attaches to the angiotensin-converting enzyme 2 (ACE2) Amelubant receptor in the host, while the S2 subunits facilitate the virus penetration into the host cells. Therefore, despite the N protein being the most abundant, the S protein is the primary target for the action of neutralizing antibodies [6,7,8,9]. In response to the urgent public health crisis presented by the COVID-19 pandemic, there has been a concerted global effort to expedite research and development processes for a vaccine. This international cooperation has yielded several types of vaccines that have undergone rigorous clinical trials and have subsequently been approved for use. The World Health Organization has sanctioned the emergency use of four primary types of vaccines: inactivated virus, RNA, non-replicating viral vector, and protein subunit vaccines [10]. Among these, inactivated vaccines, which contain a virus that has been rendered nonpathogenic, have a long history of use and are considered among the safest and most commonly utilized types of vaccines. These vaccines, distributed in billions of doses, have exhibited their effectiveness in safeguarding against a wide variety of viral and bacterial diseases. COVID-19 inactivated vaccines such as CoronaVac, BBIBP-CorV, and Covaxin have been widely used. These vaccines are prepared by inactivating cell culture viruses using chemical reagents such as -propiolactone [11]. The vaccine maintains the integrity of the virus particle test and uses the whole virus as an immunogen. Compared with subunit vaccines of S protein or RBS fragments, a broader immune response can be induced [12,13]. Clinical trial results have shown that the overall adverse effects of inactivated vaccines are low, indicating a good safety profile [14,15,16,17]. They also have good safety among different populations, such as children and adolescents, the elderly, cancer patients, pregnant women, immunocompromised people, those with comorbidities, and HIV-infected people [18]. Adjuvants are often added to vaccines to improve the efficiency of the immune response, increase the duration of protection, reduce the amount of antigen used, and provide cross-protection by enhancing the breadth of the immune response to multiple antigens. At present, more than 10 adjuvants have been used in human vaccines, including aluminum salt, MF59, CpG, AS01, AS03, AS04, liposomes, etc. Aluminum salts are the most.