Why Are Vaccines Important?

Vaccines are a fundamental part of modern medicine. They are specifically designed to safely induce an immune response, ensuring that when an individual is exposed to pathogens, they are protected against infection. According to the World Health Organization, vaccines prevent an estimated 3.5 to 5 million deaths worldwide each year. Immunization has also curbed the spread of diseases such as tetanus, diphtheria, influenza, whooping cough, and measles.

As explored in our first blog, antigens play a dual role – they are both the cause of disease and the key to combating it. Beyond their diagnostic applications, antigens are essential components in many vaccines. In this final installment of our antigen series, we’ll briefly explore different types of vaccines, key considerations in antigen design, and the emerging role of antigens in cutting-edge cancer vaccines.

Are There Different Vaccine Types?

To induce an immune response, vaccines must contain antigens. These can be directly derived from the pathogen or synthetically produced to represent pathogen components. Traditionally vaccines are classified as:

· Live attenuated vaccines – use weakened versions of the virus or bacteria, e.g. MMR injection (measles, mumps, rubella) and chickenpox vaccines. However, these pathogens may replicate uncontrollably in immunocompromised individuals, restricting their use. Read our blog Beyond Adult Models: Rethinking Vaccine Development for Children for more on this topic.

· Non-Live (inactivated) vaccines – contain pathogens that are sterilized but still have the antigens your immune system needs to initiate a response, e.g. Polio, Hepatitis A.

Advancements in vaccine research have expanded beyond traditional methods, leading to the development of new platforms such as viral vectors, virus-like particles, and more:

· Subunit, recombinant, or conjugate vaccines - only use specific antigens (like a surface protein) from the pathogen and not the whole organisms, e.g. HPV, Hepatitis B, whooping cough.

· mRNA vaccines - instead of injecting the antigen itself, these vaccines deliver mRNA to your cells to make the antigen temporarily, e.g. Pfizer-BioNTech, Moderna COVID-19 vaccines

We will discover below how these pioneering vaccine platforms are driving the development of cutting-edge cancer vaccines.

How Is Vaccine Success Measured?

The success of a vaccine is measured first in research and development labs, followed by clinical trials (Figure 1), which evaluate its effectiveness in preventing infection, reducing disease severity, or lowering hospitalization rates. Another important outcome of vaccinations is ‘herd protection’ or herd immunity, where a sufficient number of individuals are vaccinated to interrupt pathogen transmission, leading to a decrease in disease incidence.

Figure 1: Three phases of human clinical trials for vaccines

Key Antigen Characteristics for Effective Vaccines

Designing an antigen for a vaccine involves balancing immunogenicity, safety, stability, and practicality. The main factors to consider are:

Antigen epitopes – epitopes should be selected that can generate a strong immune response and are known to generate neutralizing antibodies that block infection or replication.

Cross-reactivity - reactivity with non-target organisms or host tissues should be avoided to minimize off-target effects. If multiple pathogen strains exist the antigen should ideally provide cross-protection.

Immunogenicity – an antigen needs to be immunogenic enough to trigger an immune response but not overwhelm the immune system. Depending on the type of antigen, an adjuvant may be used. Read blog 2 for more on how adjuvants increase an antigen’s immunogenicity.

Stability – some antigens need to maintain proper folding to present epitopes correctly and must remain stable under storage conditions to prolong the vaccine shelf-life. Stabilizers are added to protect the antigen from degradation due to heat, light, or other environmental factors. Common stabilizers include sugars (e.g. sucrose, lactose), gelatin, amino acids (e.g. glycine) and proteins.

Delivery method – the antigen’s design should be compatible with the method of vaccine delivery. mRNA vaccines, for instance, are usually delivered using Lipid Nanoparticles (LNPs) to protect the mRNA. Read more about LNPs in our phospholipase D blog.

Safety – the antigen should not mimic human proteins to reduce the risk of triggering autoimmune reactions or toxicity. For example, you don’t want a therapeutic vaccine to destroy healthy cells. For this reason, vaccines undergo rigorous clinical trials to ensure safety and regulatory acceptability.

Production feasibility - the antigen should be reliably reproducible in large quantities using for instance microbial, mammalian, or cell-free expression systems. Its design should also allow for economical production, especially for global distribution.

Cutting-edge Cancer Vaccines

Antigens are currently being utilized in groundbreaking vaccines to fight cancer. Cancer vaccines can be either preventive or therapeutic. Preventive vaccines aim to target infections that cause cancer, such as human papillomavirus (HPV) strains, which can lead to cervical cancer. Therapeutic vaccines, on the other hand, are administered to patients diagnosed with cancer. These vaccines stimulate the immune system to specifically destroy cancer cells using tumor-associated antigens or patient-specific neoantigens. Here are some prime examples of how antigens are applied in innovative cancer vaccines.

mRNA Vaccines

Messenger RNAs (mRNA) encoding tumor-specific antigens are delivered into the body, prompting cells to produce these antigens and trigger an immune response that targets and destroys tumor-specific antigen-presenting cells. Currently in development is Moderna and Merck’s mRNA-4157/V940 vaccine which targets 34 neoantigens specific to a patient’s tumor profile. In phase 2b clinical trials, this vaccine successfully reduced cancer recurrence in melanoma patients in combination with pembrolizumab.

Figure 2: mRNA vaccine

DNA Vaccines

Tumor antigens are delivered into host cells using plasmid DNA. Inovio Pharmaceutical’s DNA vaccine, INO-5401, is currently in phase 1 clinical trials for its use in BRCA1 or BRCA2 cancer patients.

Peptide-Based Vaccines

Peptides corresponding to tumor-specific antigens and tumor-associated antigens are introduced into the body, where they are processed and displayed by antigen-presenting cells. Consequently, helper T cells and cytotoxic T lymphocytes are activated, driving the immune system to target tumor cells expressing these antigens. One such vaccine undergoing clinical trials is Mimivax’s SurVaxM. This vaccine targets survivin, a cell-survival protein found in 95% of glioblastomas and other cancer types.

Read our blog showcasing Evaxion’s Phase II Trial for personalized neoantigen peptide cancer vaccines against metastatic skin cancer, for which Biosynth supplies personalized peptide pools.

Viral Vector Vaccines

Host cells use genetic material carried by viral vectors to express tumor antigens. T-VEC is a viral vector vaccine approved by the FDA for metastatic melanoma. This vaccine uses an oncolytic herpes simplex virus type 1 (HSV-1) which can replicate specifically in tumor cells. It also has the ability the lyse tumor cells while generating systemic antitumor immunity through the expression of granulocyte-macrophage colony-stimulating factor.

Cell-Based Vaccines

Cell-based vaccines use whole cells, which can be either patient-derived or donor-derived, to present tumor antigens and generate an immune response. The types of cell-based vaccines are:

· Dendritic cell vaccines - dendritic cells are extracted from a patient, loaded with tumor-associated antigens, and reinfused to target T-cells.

· Tumor cell vaccines - irradiated tumor cells are modified to produce immune-stimulating factors, such as granulocyte-macrophage colony-stimulating factor, for an enhanced immune response.

An example of a dendritic cell vaccine is Sipuleucel-T, designed for metastatic castration-resistant prostate cancer. This therapy involves isolating peripheral blood mononuclear cells from the patient, which are then cultured with a recombinant fusion protein (PA2024) composed of prostatic acid phosphatase (PAP) linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). Once activated, these cells are reinfused into the patient to stimulate a T-cell-driven immune response specifically targeting prostate cancer cells that express PAP.

Biosynth’s Antigens For Vaccine Research

Vaccines are proving to be a weapon against human disease, but there are still more discoveries to be made. A greater understanding is needed to develop vaccines against hard-to-target pathogens like the tuberculosis-causing pathogen Mycobacterium tuberculosis, antigenically variable pathogens namely HIV, and pathogens like Dengue virus, Ebola and COVID-19 that cause outbreaks of public health concern.

Unlock the power of research with our premium collection of native and recombinant antigens, perfect for advancing vaccine development against infectious diseases, cancer and beyond. Explore our full range today and discover the tools that can accelerate your breakthroughs. Need something unique? Our scientists can craft custom-designed antigens tailored to your research needs. Browse our antigens or learn more about our custom antigen design services – your next discovery starts here.

That concludes our three-part antigen blog series, delving into the use of antigens as diagnostics tools, how to design an antigen for antibody production and finally the critical role that antigens play in vaccines.

References

Pollard, A. J., Bijker, E. M. (2021). A guide to vaccinology: from basic principles to new developments. Nature Reviews Immunology, 21, 83-100.

World Health Organization. (2020). How are vaccines developed? https://www.who.int/news-room/feature-stories/detail/how-are-vaccines-developed

Adam, J. (2024). The rise of cancer vaccines: A new era in immunotherapy. LABIOTECH, https://www.labiotech.eu/in-depth/cancer-vaccines/