Nanoparticles for Therapeutic Cargos —Vaccines

In recent years, nanotechnology has created its space in vaccinology. Nanocarriers are suitable delivery vehicles for vaccines due to the enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. What’s more, nanoparticles have been shown capable of not only desirable vaccine release, but can also be targeted to immune cells of interest, loaded with immunostimulatory substances termed adjuvants, or even induce desirable immune activating effects on their own. CD Bioparticles is experienced in providing vaccine carriers such as polymeric nanoparticles, nanocapsules, liposomes, micelles, dendrimers, nanotubes for your need.

Vaccines Introduction

Vaccines are designed immunogenic antigens used to intentionally trigger the memory component of the immune system by stimulating humoral immunity via the production of antibodies for long term protection against various diseases. These agents resemble a disease-causing microorganism and stimulate the body’s immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily challenge these microorganisms upon subsequent encounters. Vaccination is the most effective means of controlling infectious disease-related morbidity and mortality nowadays.

So far, there are several types of vaccines available, including inactivated vaccines, attenuated vaccines, genetic engineering recombinant protein vaccines, viral vector vaccines, and nucleic acid vaccines. Each type of vaccine induces different levels, scope, and duration of immune responses, as well as different parts of the body where the immune effect takes place. Among them, genetic engineering recombinant protein vaccines, viral vector vaccines, and nucleic acid vaccines have advantages such as artificial modification and rapid construction, and play a crucial role in responding to new outbreaks of infectious diseases and reinfections caused by highly variable and polymorphic pathogens.

• Inactivated Vaccines

Inactivated vaccines are a traditional type of vaccine that uses chemical or physical methods to process natural viruses, resulting in a vaccine that has no infectivity but retains the natural antigenic epitopes of the virus. Inactivated vaccines can be further divided into whole microorganism inactivated vaccines, split vaccines, and virus-purified subunit vaccines through centrifugation and chromatographic techniques for purification and component separation. Inactivated vaccines have the advantages of good safety, fast development speed, and the ability to simultaneously present multiple antigens. However, they also have limitations, including weaker immunogenicity, weaker induction of cellular immune responses, and the risk of antibody-dependent enhancement (ADE) of infection.

• Attenuated Vaccines

Attenuated vaccines refer to vaccines where the virus's virulence genes are either absent or modified through genetic engineering or other means to maintain the original immunogenicity while reducing or eliminating the virus's replication ability. Depending on the method used to obtain the attenuated vaccine, it can include attenuated vaccines derived from weak animal viruses, attenuated vaccines obtained through cell or animal passage, cold-adapted attenuated vaccines, genetically modified virus virulence gene-deficient attenuated vaccines, and genetically recombined virus vaccines.

• Genetic Engineering Recombinant Protein Vaccines

Genetic engineering recombinant protein vaccines refer to virus protein vaccines obtained by expressing virus antigen proteins through genetic engineering methods in various expression cells, including prokaryotic and eukaryotic cells. Based on differences in vaccine antigen components and assembly, genetic engineering recombinant protein vaccines include peptide vaccines, recombinant subunit vaccines, and virus-like particle (VLP) vaccines.

• Viral Vector Vaccines

Viral vector vaccines are a new type of vaccine in which the internal genome of the virus particle has been modified through genetic engineering techniques to include one or more antigen genes of the target virus. After infecting the human body, viral vector vaccines induce immune responses against the target virus by expressing the antigen protein of the target virus. Depending on whether the virus vector retains the gene fragments related to viral vector replication, viral vector vaccines can be divided into replicating viral vector vaccines and non-replicating viral vector vaccines.

• Nucleic Acid Vaccines

Nucleic acid vaccines are a new type of vaccine that is referred to as the 3rd generation vaccine technology. This type of vaccine includes DNA and RNA vaccines. To be effective, nucleic acid vaccines need to be delivered into the host cells through lipid nanoparticles or electroporation, where they undergo protein translation and post-translational modifications. Nucleic acid vaccines present antigens in their natural form and can induce both cellular and humoral immune responses. Antigens are presented to CD8+ T cells via the major histocompatibility complex (MHC) class I pathway, inducing specific cytotoxic T lymphocytes (CTLs) and cell-mediated immune responses. Antigens are also presented to CD4+ T cells via the MHC class II pathway, stimulating B cells to produce specific antibodies and humoral immune responses. Nucleic acid vaccines have the advantage of shorter development and update time compared to traditional vaccines, and do not carry the risk of viral vector infection.

DNA vaccines require the optimization and construction of expression vectors, gene modification and codon optimization, adjuvant selection, and process optimization. Currently, only animal DNA vaccines such as DNA vaccines for horses to prevent West Nile virus infection and H5 subtype avian influenza DNA vaccines are on the market. There are many DNA viral vaccines under development for humans, including SARS-CoV-2 (INO-4800), influenza virus, SARS-CoV, MERS-CoV, HIV, ZIKV, and Rift Valley fever virus (RVF).

mRNA vaccines are an innovative type of vaccine that has strong immunogenicity, simple and rapid preparation, and easy scalability. They have played an incomparable role in responding to the COVID-19 pandemic compared to other vaccine types. The construction, production, purification, and adjuvant of mRNA vaccines are universal for different pathogens, and multiple pathogen vaccines can be produced in a mature facility, significantly reducing the cost and time of vaccine production. Depending on whether they contain subgenomic promoters and open reading frames (ORFs) encoding RNA-dependent RNA polymerase, mRNA vaccines include non-replicating mRNA vaccines and self-amplifying mRNA vaccines. The gene sequence of mRNA vaccines includes basic elements such as 5' cap structure, 5' untranslated region (UTR), target gene ORF, 3'UTR, and 3' poly A tail, which play an important role in producing stable mature mRNA, extending mRNA half-life, and enhancing mRNA translation. Currently, mRNA viral vaccines on the market and under development include SARS-CoV-2 vaccines (mRNA-1273, BNT162b2), influenza virus vaccines (HA mRNA-LNP), RSV vaccines, ZIKV vaccines, EBOV vaccines, and HIV vaccines, among others.

Nanocarrier based payload cargos for vaccines are growing technologies due to their intrinsic immune-stimulatory properties, ability to co-entrap antigen adjuvants such as toll-like receptor (TLR) and enhancement of the antigen uptake by cells, e.g., by professional antigen presenting cell (APC) manipulation. They are widely used to augment immunogenicity of antigens, to protect vaccines from degradation in the physiological environment, to improve the efficacy of vaccines, and to target specific sites preventing unwanted accumulation. Tailored nanocarriers can safely cargo vaccines to a specific site. Attempts are being made to deliver vaccines through carriers as they control the spatial and temporal presentation of antigens to the immune system thus leading to their sustained release and targeting. Hence, lower doses of weak immunogens can be effectively directed to stimulate immune responses and eliminate the need for the administration of prime and booster doses as a part of conventional vaccination regimen.

Advantages of nanocarrier based vaccine delivery system possess the following significant advantages:

• Because of the small size owned by nanoparticles, they display remarkable properties like high surface area to volume ratio and high diffusion rate. And these carriers are better taken up by the antigen presenting cells thereby facilitating the delivery of antigen to the antigen presenting cells;
• Localized drug delivery is possible with targeted nanocarriers;
• Increased bioavailability with nanocarrier dependent therapeutics;
• Apart from carriers, they also work as an adjuvant to provoke the immune response and thus produce lager response as compared with conventional vaccines;
• Can maximize drug concentration at mucosal surfaces without causing harm to the body.

Of course, not all materials can be suitable vaccine carriers. The components used for formulating nanocarriers should be nonreactive and preferably biocompatible. The release of the vaccines from nanocarriers follows any of the mechanisms, alone or in combination, including erosion, degradation, diffusion or swelling of the matrix. Nanocarrier should provide optimum encapsulation, enough stability and necessary permeability to the antigen/drug. As a result, carriers such as polymeric nanoparticles, nanocapsules, liposomes, bilosomes, micelles, dendrimers and nanotubes which are now being investigated and developed as vaccine delivery carriers.

Figure 1. Schematic representation of different vaccine nanocarriers. (Smith, J. D., Morton, L. D., Ulery, B. D. Current opinion in biotechnology, 2015, 34, 217-224.)

Our Featured Services

CD Bioparticles is specialized in the development of drug delivery systems and customizing nanoparticles for vaccine delivery utilizing our core technologies. With our high-quality products and services, the efficacy of your vaccine delivery can be tremendously improved.

We can help you choose appropriate vaccines and carrier materials for your special needs. And we are proficient in designing and synthesizing polymeric nanoparticles, nanocapsules, liposomes, micelles, dendrimers, nanotubes and other nanocarriers for vaccine delivery. Carrier properties such as molecular weight, solubility, and hydrophobicity could be designed and engineered at your will; as well as the addition of desired chemical groups or targeting moieties for further functionalization.

References:
1. Gregory, A. E., Williamson, D., Titball, R. Vaccine delivery using nanoparticles. Frontiers in cellular and infection microbiology, 2013, 3, 13.
2. Wen, R., Umeano, A., Francis, L., Sharma, N., Tundup, S., Dhar, S. Mitochondrion: a promising target for nanoparticle-based vaccine delivery systems. Vaccines, 2016, 4(2), 18.
3. Singh, M., Chakrapani, A., O’Hagan, D. Nanoparticles and microparticles as vaccine-delivery systems. Expert review of vaccines, 2007, 6(5), 797-808.
4. Saroja, C. H., Lakshmi, P. K., Bhaskaran, S. Recent trends in vaccine delivery systems: a review. International journal of pharmaceutical investigation, 2011, 1(2), 64.