ABSTRACT
SARS-CoV-2 infections present a tremendous threat to public health. Safe and efficacious vaccines are the most effective means in preventing the infections. A variety of vaccines have demonstrated excellent efficacy and safety around the globe. Yet, development of alternative forms of vaccines remains beneficial, particularly those with simpler production processes, less stringent storage conditions, and the capability of being used in heterologous prime/boost regimens which have shown improved efficacy against many diseases. Here we reported a novel DNA vaccine comprised of the SARS-CoV-2 spike protein fused with CD40 ligand (CD40L) serving as both a targeting ligand and molecular adjuvant. A single intramuscular injection in Syrian hamsters induced significant neutralizing antibodies 3-weeks after vaccination, with a boost substantially improving immune responses. Moreover, the vaccine also reduced weight loss and suppressed viral replication in the lungs and nasal turbinates of challenged animals. Finally, the incorporation of CD40L into the DNA vaccine was shown to reduce lung pathology more effectively than the DNA vaccine devoid of CD40L. These results collectively indicate that this DNA vaccine candidate could be further explored because of its efficacy and known safety profile.
Subject(s)
CD40 Ligand/immunology , COVID-19/immunology , Mesocricetus/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/immunology , Adjuvants, Immunologic/pharmacology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/virology , Cell Line , Female , HEK293 Cells , Humans , Lung/immunology , Lung/virology , Mesocricetus/virology , Models, Animal , Vaccination/methods , Vaccines, Inactivated/immunologyABSTRACT
SARS-CoV-2 infections present a tremendous threat to public health. Safe and efficacious vaccines are the most effective means in preventing the infections. A variety of vaccines have demonstrated excellent efficacy and safety around the globe. Yet, development of alternative forms of vaccines remains beneficial, particularly those with simpler production processes, less stringent storage conditions, and the capability of being used in heterologous prime/boost regimens which have shown improved efficacy against many diseases. Here we reported a novel DNA vaccine comprised of the SARS-CoV-2 spike protein fused with CD40 ligand (CD40L) serving as both a targeting ligand and molecular adjuvant. A single intramuscular injection in Syrian hamsters induced significant neutralizing antibodies 3-weeks after vaccination, with a boost substantially improving immune responses. Moreover, the vaccine also reduced weight loss and suppressed viral replication in the lungs and nasal turbinates of challenged animals. Finally, the incorporation of CD40L into the DNA vaccine was shown to reduce lung pathology more effectively than the DNA vaccine devoid of CD40L. These results collectively indicate that this DNA vaccine candidate could be further explored because of its efficacy and known safety profile.
ABSTRACT
The huge worldwide demand for vaccines targeting SARS-CoV-2 has necessitated the continued development of novel improved formulations capable of reducing the burden of the COVID-19 pandemic. Herein, we evaluated novel protein subunit vaccine formulations containing a resistin-trimerized spike antigen, SmT1. When combined with sulfated lactosyl archaeol (SLA) archaeosome adjuvant, formulations induced robust antigen-specific humoral and cellular immune responses in mice. Antibodies had strong neutralizing activity, preventing viral spike binding and viral infection. In addition, the formulations were highly efficacious in a hamster challenge model reducing viral load and body weight loss even after a single vaccination. The antigen-specific antibodies generated by our vaccine formulations had stronger neutralizing activity than human convalescent plasma, neutralizing the spike proteins of the B.1.1.7 and B.1.351 variants of concern. As such, our SmT1 antigen along with SLA archaeosome adjuvant comprise a promising platform for the development of efficacious protein subunit vaccine formulations for SARS-CoV-2.
Subject(s)
Adjuvants, Immunologic/chemistry , Antigens, Archaeal/chemistry , COVID-19 Vaccines/therapeutic use , Lipids/chemistry , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Body Weight , COVID-19/therapy , Chlorocebus aethiops , Cricetinae , Cytokines/metabolism , Female , Humans , Immunity, Cellular , Immunity, Humoral , Immunization, Passive , Mesocricetus , Mice , Mice, Inbred C57BL , Neutralization Tests , Peptides/chemistry , Protein Domains , SARS-CoV-2 , Toll-Like Receptors/immunology , Vero Cells , Viral Load , COVID-19 SerotherapyABSTRACT
The pandemic outbreak of COVID-19, caused by coronavirus SARS-CoV-2, created an unprecedented challenge to global public health system and biomedical community. Vaccination is an effective way to prevent viral infection, stop its transmission, and develop herd immunity. Rapid progress and advances have been made to date in the development of COVID-19 vaccines. Currently, more than 115 vaccine candidates have been developed from different technology platforms with several of them in clinical trials. Most of those vaccine candidates are developed based on the experience with other coronaviruses with an aim to induce neutralizing antibodies against the viral spike protein or its different receptor binding domains. Here, we discuss the promise, potential scientific challenges, and future directions for the development of a safe and effective COVID-19 vaccine. We also emphasize the importance of a better understanding of the infection pathogenesis and host defense mechanisms against SARS-CoV-2 infection.