What Are Subunit Vaccines?
Vaccines are proven powerful weapons against many human diseases, especially infectious diseases. A subunit vaccine is a vaccine that presents one or more antigens to the immune system without introducing pathogen particles, whole or otherwise. The word “subunit” simply means the antigen is a fragment of the pathogen, and the antigens involved can be any molecule, such as proteins, peptides, or polysaccharides.
Although inactivated or attenuated virus vaccines based on the whole cell structure have achieved great success, they have many shortcomings. First, they need to deal with highly active virus strains, so they must be developed in a laboratory with specific specifications. Secondly, their antigen components are diverse, thus the immune response caused by them is more complex and intense.
To circumvent these problems, some subunits of the pathogen that can induce the specific immune response of the human body are prepared as vaccines, thereby avoiding the side effects caused by viral replication and the unwanted immune response, and greatly improving the safety of the vaccine. However, a disadvantage of these high-purity subunit vaccines is that due to the lack of many intrinsic characteristics of the pathogen, their immunogenicity is generally not high, which makes it difficult to induce a specific immune response in vivo. Therefore, adjuvants are added to stimulate the body’s immune response, to improve the body’s ability to respond to such subunit vaccines.
Adjuvants are an immunologic substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens. There are two major types of adjuvants, vaccine delivery vehicles, and immunostimulants. Vaccine Delivery Vehicles are used to prolong antigen availability or promote antigen uptake by multimerization or physical incorporation into particles of an optimal size for efficient uptake by the macrophages resulting in enhanced and targeted presentation to T-cells and stimulation of B-cells. Examples include aluminum salts-based, Liposomes, micro/nanoparticles, virus-like particles (VLPs), and emulsions. Immunostimulants or immunostimulatory adjuvants are used to promote signaling events that result in cellular activation, such as producing proinflammatory cytokines and chemokines necessary for efficient presentation of vaccine antigen to native T-cell. Examples include cytosine-phosphate guanosine (CpG), monophosphoryl lipid A (MPA), and toll-like receptor ligands (TLRs).
Recombinant Protein Subunit Vaccines
With the advances made in structural biology and protein engineering, recombinant subunit vaccines for various infections are possible. Recombinant protein subunit vaccines are composed of at least one type of viral antigen that can be produced in heterologous expression systems. Recombinant protein subunit vaccines are significantly more secure than live attenuated and inactivated/killed vaccines. In addition, recombinant protein subunit vaccines can be scaled up more cost-effectively compared with other types of vaccines. In the past 3 decades, there has been a trend toward developing subunit vaccine formulations that contain precisely specified antigenic components in conjunction with a potent adjuvant.
This immunogenic deficiency of subunit vaccines is specifically due to the structural and conformational distortions of these subunits. In particular, the spike (S) protein of SARS-CoV-2 usually binds to the host cell surface receptor ACE2 in the form of a trimer and mediates subsequent virus entry in vivo, thus the trimer S protein would theoretically have better immunogenicity. Protein structural biology and engineering provide novel technologies to simulate the original pathogen protein structure to increase the immunogenicity of subunit vaccines. For instance, some recombinant protein antigens can spontaneously assemble into virus-like particles (VLPs) that are multiprotein structures without incorporating the actual viral genome. VLPs are useful as vaccines. VLPs contain repetitive, high-density displays of viral surface proteins that present conformational viral epitopes that can elicit strong T cell and B cell immune responses, the particles’ small radius of roughly 20-200 nm allows for sufficient draining into lymph nodes.
Malvern Panalytical Technology Solutions
For any vaccine development platform, Malvern Panalytical offers solutions to advance products from early-stage discovery to late-stage manufacturing and process control. These solutions for 2nd generation recombinant protein VLP vaccines development are listed below.
Formulation Stability and Aggregate Formation
Zetasizer Advance Range with Dynamic and Electrophoretic Light Scattering Capabilities to probe the presence of unwanted aggregates and measure surface charge and zeta potential to assess formulation stability.
Conformational and Thermal Stability
The MicroCal PEAQ-DSC is a great tool for understanding conformational and thermal stability by obtaining multiple descriptors of thermal transitions and obtaining fingerprints of Higher Order Structure of recombinant proteins.
Particle Size, Distribution, and Concentration
NanoSight NS300 is a real-time nanoparticle visualization system based on Nanoparticle Tracking Analysis (NTA) where a laser-illuminated microscope detects Brownian motion of and counts VLPs in solution. Another technology solution for concentration determination of VLPs with size range < 40 nm, is the Zetasizer Ultra which is based on Multi-Angle Dynamic Light Scattering (MADLS) to count photons and calculates particle concentration from other measured or known sample properties, including size, refractive index, viscosity, and buffer scatter rate.