Some publications have reported that SARS-CoV-2 spike RBD proteins induced functional antibody response with acceptable safety profile in non-human primates [11, 12]

Some publications have reported that SARS-CoV-2 spike RBD proteins induced functional antibody response with acceptable safety profile in non-human primates [11, 12]. This fusion protein was expressed in CHO and formulated with alternative adjuvants with different immune activation including Montanide ISA51, Poly (I:C), and MPLA/Quil-A? as potential vaccine candidate formulations. Using the murine model, a potent induction of anti-RBD IgG antibodies in immunized mice sera were observed. IgG subclass analyses (IgG1/IgG2a) illustrated that all adjuvanted formulations could stimulate both Th1 and Th2-type immune responses in particular Poly (I:C) and MPLA/Quil-A?, eliciting greater balance. In addition, Montanide ISA51-formulated RBD-Fc vaccination provided a promising level of neutralizing antibodies against live wild-type SARS-CoV-2 followed by Poly (I:C) and MPLA/Quil-A?, respectively. Kinesore Also, mice sera from adjuvanted formulations could strongly inhibit RBD:ACE2 interaction. This study offers immunogenicity profiles, forecasted safety based on Vaccine-associated enhanced disease (VAED) caused by Th1-skewed immunity, and neutralizing antibody analysis of candidates of RBD-Fc-based subunit vaccine formulations to obtain an alternative subunit vaccine formulation against SARS-CoV-2. Introduction The outbreak of novel coronavirus (SARS-CoV-2) has increasingly become a global threat to humanity. Since the initial outbreak in the city of Wuhan in Chinas Hubei province in January 2020, there has been more than 700 million confirmed cases with nearly 7 million deaths globally [1]. This novel pathogen, the cause of COVID-19, causes fever, severe respiratory illness, and pneumonia. A promising approach to control Kinesore its spread and prevent future outbreaks is the effective vaccination against SARS-CoV-2. To date various types of vaccines such as mRNA, viral vector, protein, and DNA-based vaccines have been shown to induce a strong neutralizing antibody response in animal models as well as humans [2C8]. Two mRNA-based and two adenovirus-based vaccines have been approved by the FDA and EMA whereas more than 50 candidates are still under clinical trials [9]. Many vaccines are still effective against the variants of SARS-CoV-2, however, as more variants continue to emerge, they must still be modified and adapted to tackle future variants. This situation has prompted scientists to continue developing vaccine candidates to prevent future outbreaks and ensure sufficient vaccine availability for low- and middle-income countries. Immunogen design of SAR-CoV-2 vaccine candidates mostly exploit the spike (S) of SARS-CoV-2. The S proteins of SARS-CoV-2 are abundantly exposed at the surface of the virus and are vital for virus entry into host cells. Hence, the design of novel vaccines should focus on neutralizing the S proteins by antibodies. This homotrimer protein utilizes its two functional subunits; S1 subunit binds to the host cell receptors and S2 subunit is responsible for the fusion of the viral and host cellular membranes. Within the S1 subunit, there is a receptor-binding domain (RBD) Kinesore that binds to human Angiotensin converting enzyme 2 (ACE2) which mediates viral entry into host cells and stabilizes the prefusion state of the virus. Instead of full-length S proteins, RBD (the S fragment) or its fusion with the Fc domain of human IgG1 (RBD-Fc) has been used as a subunit vaccine candidate for SARS-CoV. Several studies demonstrated that RBD and RBD-Fc could elicit potent neutralizing antibodies with no report of complications [10]. Some publications have reported that SARS-CoV-2 spike RBD proteins induced functional antibody response with acceptable safety profile in non-human primates [11, 12]. RBD is an attractive target for developing vaccines against other related coronaviruses (such as MERS-CoV and SAR-CoV) due to promising interference of the binding between RBD and its host cell receptors. This makes RBD-based subunit vaccines a key candidate for SARS-CoV-2 [13, 14]. Recently, many subunit vaccine candidates against COVID-19 have been developed based on SARS-CoV-2 spike RBD e.g., ZF2001, an RBD-dimer (residues 319C537 in tandem repeat) produced in Chinese Hamster Ovary (CHO) cells developed at Anhui Zhifei Rabbit Polyclonal to UBR1 Longcom Biopharmaceutical along with the Chinese Institute of Microbiology, Academy of Sciences [15]. This candidate was reported to have increased stability and could induce the production of RBD-specific IgG and neutralizing antibody in mouse model. Currently this vaccine candidate is under Phase 3 clinical trial [16]. Another study where.