Nanocarrier vaccines for SARS-CoV-2

Abstract

The SARS-CoV-2 global pandemic has seen rapid spread, disease morbidities and death associated with substantive social, economic and societal impacts. Treatments rely on re-purposed antivirals and immune modulatory agents focusing on attenuating the acute respiratory distress syndrome. No curative therapies exist. Vaccines remain the best hope for disease control and the principal global effort to end the pandemic. Herein, we summarize those developments with a focus on the role played by nanocarrier delivery.

Keywords: COVID-19 vaccine; Nanovaccine; SARS-CoV-2; mRNA vaccine.

Graphical abstract

Fig. 1

SARS-CoV-2 vaccine designs. Live-attenuated viruses are produced by serial passage in relevant tissue culture systems. Virus inactivation is produced by radiation, heat, or chemical treatments. Both live-attenuated and inactivated viruses are capable of inducing protective antiviral immune responses. Viral vectors are employed to deliver specific antigens through the genome of another virus. DNA vaccines, carried by recombinant bacterial vectors, are generated in relevant microorganisms or in cell cultures. When injected into a host they provide relevant virus-specific protein synthesis needed to generate an immune response. Recombinant subunits are antigenic determinants of SARS-CoV-2, obtained by recombinant DNA technology. VLPs contain no genetic materials but resemble the SARS-CoV-2 virus by virtue of specific surface antigenic proteins. Broadly neutralizing antibodies (bNAbs) are capable of binding to multiple conserved sites on viral spike proteins obtained from different viral strains, and thereby prevent virus neutralization escape. They may also function to attenuate virus evolution. Synthetic peptides can be designed to inhibit the receptor-binding domain (RBD) on the spike protein that is crucial for SARS-CoV-2 to gain host cell entry. Nanoparticles and extracellular vesicles (EVs) are the emerging technologies for the degevelopment of safer vaccines against SARS-CoV-2. Nanoparticles are decorated with antigenic molecules, while EVs serve as natural carrier of viral proteins, wherein both inducing antiviral immune responses.

Fig. 2

Schematics for vaccine-induced antiviral immunity. DNA vaccines carry viral genes, which are released inside the target APCs. The inserted genes are transcribed, then translated to antigenic viral proteins that are either presented through the APC to CD8 T cells through MHC-I TCR interactions. Alternatively, the viral protein of interest is presented to CD4 T cells by MHC-II TCR interactions. Cytotoxic CD8 T cells kill infected cells and B cells make antibodies by CD4 T cell dependent activation. These released antibodies are directed to target specific viral antigens. RNA vaccines incorporate mRNA into target APCs and undergo parallel pathway events once the immunogenic proteins are synthesized. Subunit vaccine consists of the antigenic determinants of the viral pathogen, which enters the target cells and subsequently releases the specific viral subunits. The subunits are engulfed into endosomes, which when fused with the membranes, present the viral antigens to the CD4 T cells for both T- and B- cell mediated antiviral immunity. Multivalent viral vaccines are also designed to display multiple antigens in order to enhance immunogenicity. Abbreviations; Antigen presenting cells, APCs; class I major histocompatibility complex, MHC-I; class II major histocompatibility complex, MHC-II, T-cell receptor,TCR; B-cell receptor, BCR. The illustration is prepared in-house and schematic ideas and technical details were followed as presented in previous published report [17].

Fig. 3

Two-vector viral vaccines. Developed by Gamaleya Center in Russia, two-vector vaccine, as the name suggests, uses two different vectors (Ad5 and Ad26). Vector development involves the use of S-protein mRNA to generate the complementary DNA, followed by insertion of this S-protein encoding DNA into adenoviral vectors, Ad26 and Ad5. Ad26 vector encoding S-protein was administered as first vaccination followed by a booster dose of Ad5 vector encoding the same S-protein 21 days later. Inside the recipient, these vectors generate the S-proteins, which upon entering the circulation induces protective immunity. The illustration is prepared in-house and schematic ideas and technical details were followed as presented in previous published report [186,187].

Fig. 4

Targeted delivery of SARS-CoV-2 antigens. Nanoparticles are decorated on the surface to present SARS-CoV-2 antigens to efficiently enter APCs. Lymphatic drainage of the nanoparticles brings them in close proximity to the immune cells, particularly the APCs. Nanoparticles stimulate the APCs in different ways. APCs engulf the nanoparticles into endosomes and then presents the NP's surface engineered antigen to CD8 T lymphocytes via membrane-bound MHC-I and TCR interactions. Also, nanoparticles are ligands for the TLRs, which activates the APCs and induce secretion of pro-inflammatory cytokines. Following the interaction between MHC-I and TCR, in the presence of co-stimulatory molecules and cytokines, the activated CD8 T cells kill the infected cells by inducing cytotoxicity. Nanoparticles surface engineered antigens can also be presented to helper CD4 T cells via MHC-II. Subsequently, CD4 T cells activate the B cells to produce protective antibodies against the SARS-CoV-2 antigen. Abbreviations; Antigen presenting cells, APCs; class I major histocompatibility complex, MHC-I; class II major histocompatibility complex, MHC-II; T-cell receptor,TCR; Toll-like receptor, TLR.

Fig. 5

Schematic of nanoparticles used as a decoy to the SARS-CoV-2 virus. Polymeric nanoparticle cores are wrapped with cell membranes derived from SARS-CoV-2 target cells, human lung epithelial type II cells, or macrophages. The inheritance of the surface antigenic profiles of the target cells allows the nanosponges to act as decoys to the circulating viruses and be independent of the status of mutation and strain. They serve to prevent virus entry to the host's natural target cells. The illustration is prepared in-house and schematic ideas and technical details were followed as presented in previously published report [314].

Fig. 6

Treatments for COVID-19. Currently, repurposed and recently approved antiviral agents are used to suppress COVID-19 disease complications that include the signs and symptoms of ARDS. A number of immunotherapies are being used and are currently being tested in randomized clinical trials of COVID-19. Vaccines are the principal challenge for SARS-CoV-2 to achieve herd immunity and eliminate SARS-CoV-2 infection and its consequences. Passive immunity can be achieved by convalescent plasma or neutralizing antibodies from recovered COVID-19 patients. Additionally, radiation and CRISPR based genome editing technologies are under development for the SARS-CoV-2 elimination.