Vaccine Therapeutics Overview

Vaccine Therapeutics

• Vaccines are biological preparations that induce active acquired immunity to a specific infectious disease.
• Vaccines can be prophylactic (prevent future infection) or therapeutic (fight existing disease like cancer).
• Vaccination aims to limit infectious disease spread and protect unvaccinated individuals.

Lecture Objectives

• Understand the need for vaccination in the general population, including herd immunity.
• Differentiate between prophylactic and therapeutic vaccines, and their applications.
• Understand vaccine types (e.g., live attenuated, inactivated, subunit), their mechanisms of action, advantages, and limitations.
• Discuss suitable vaccine types against specific pathogens or cancers.
• Describe the mechanisms of action, limitations, challenges, and future directions of mRNA and cancer vaccines.

Terminology

• A vaccine is a biological preparation that provides active acquired immunity to a particular infectious disease.
• Vaccines can be prophylactic (to prevent future infection) or therapeutic (to target a disease already present, like cancer).
• Vaccination aims to reduce the spread of infectious disease and protect those unable to be vaccinated.

Vaccine Stimulates Protective Immune Response

• Vaccines stimulate an initial immune response creating protective immunity.
• This response produces immunological memory resulting in a robust response to subsequent exposure to the antigen.
• Exposure to an infection, either mild or inapparent, also activates the immunological memory.

Generation of Immune Response

• Vaccine antigens are taken up by dendritic cells (DCs) in muscle and transported to lymph nodes.
• Peptide presentation of vaccine antigen on MHC molecules activates T cells.
• T-cell signaling activates B cells to produce antibodies that recognize and neutralize the pathogen.
• Memory B and T cells are formed ensuring long-term immunity.

Brief History of Vaccination

• Edward Jenner developed the smallpox vaccine in 1796.
• Louis Pasteur introduced vaccination against rabies in 1885.
• Advances led to the near eradication of smallpox and significant reduction in polio cases.
• mRNA vaccine research began in the 1990s.

Global Vaccination Scale

• Data on polio and measles vaccination highlights the impact on case rates.
• Significant reductions in reported cases of polio and measles are observed, emphasizing the effectiveness of vaccines.

Herd Immunity

• Herd immunity occurs when a critical vaccination level is reached, protecting the population.
• This critical threshold varies depending on the pathogen's characteristics and population density.
• Achieving herd immunity prevents infection spread among susceptible individuals.

Herd Immunity Details

• Virus spread stops when the probability of infection drops below a critical level.
• This critical level is population and virus-specific.
• For polio (not highly contagious), vaccine coverage of about 80-85% is needed; 90-95% for measles (highly contagious).
• None of the vaccines is perfectly effective; an 80% critical level requires approximately 89% vaccination.

Prophylactic and Therapeutic Vaccines

• Prophylactic vaccines prevent disease.
• Therapeutic vaccines treat existing disease.

Vaccine Types

• Live attenuated: weakened form of the pathogen.
• Inactivated: killed whole organism.
• Subunit: purified components of the pathogen (e.g., protein, polysaccharide).
  • Outer membrane vesicles (OMVs): derived from the pathogen's outer membrane.
  • Toxoid: inactivated bacterial toxins.
• Nucleic acid (mRNA, DNA): genetic material coding for antigenic proteins.
• Viral vector: harmless virus carrying pathogen genes.
• Bacterial vector: live bacteria delivering pathogen genes.

Live Attenuated Vaccine

• Use of a weakened/attenuated form of the pathogen.
• Strong, long lasting immunity possible following vaccination, but it is risky since it can revert to its pathogenic form potentially affecting immunocompromised patients hence less rapid and easy new version development.
• Licensed vaccines utilizing live attenuated technology: measles, rubella, mumps, influenza, oral polio, typhoid, Japanese encephalitis, rotavirus, BCG, varicella zoster

Inactivated Vaccine

• Use of a killed, non-living pathogen.
• Lower adverse side effects but usually necessitates multiple booster shots to maintain efficacy.
• Licensed vaccines utilizing this technology: whole-cell pertussis, polio, influenza, Japanese encephalitis, rabies, hepA

Influenza A Virus

• Classified by subtypes based on hemagglutinin (H) and neuraminidase (N) proteins.
• Subtypes are named by combining H and N numbers.

Inactivated Influenza Vaccine

• Virus grown in embryonated chicken eggs, inactivated using formalin or detergent.
• 60% effective.
• Envelope proteins change yearly, requiring the selection of new strains for yearly vaccine design.

Selecting an Influenza Virus Vaccine

• Surveillance network tracks virus strains for seasonal vaccine composition.
• The process involves selection of virus strains, developing reassortant viruses, standardizing antibodies, and determining dosages.

Outer Membrane Vesicle Vaccines

• Outer membrane vesicles (OMVs) are used to present antigens to the immune system.
• Antigens from the outer membrane of pathogens are used for vaccination to aid the immune systems response and improve efficiency.
• Advantages include straightforwardness, while limitations include yield consistency and toxicity concerns

Subunit (Purified Protein, Rec. Protein, Peptide, Polysaccharide)

• Uses purified parts of pathogens.
• Can be recombinant, thus easily manufactured and safe for immunocompromised patients, but often necessitates adjuvants for improved immunity.
• Widely used but expensive.

Protein-Polysaccharide Conjugate

• Combines polysaccharide with a carrier protein to enhance immune response, particularly effective in children.
• Licensed vaccines: Haemophilus influenzae type B, pneumococcal, meningococcal, typhoid

Virus-like Particles (VLPs)

• Mimic viral structure, not containing viral genome; non-infectious.
• Robust immunogenic stimulation and wide applicability.
• Limitations include often liquid formulations, storage issues, and boosters needed.

Human Papillomavirus (HPV) Vaccine

• Prevents certain high-risk HPV types associated with cancer.
• Currently available vaccines target specific HPV types that can cause cancer or warts.

Antigen-Presenting Cell Vaccine

• Uses antigen-presenting cells (APCs) for cancer vaccination.
• Goal is to activate T cells against tumor-associated antigens to bolster immunity against tumor.

Process of generating whole cell DC vaccine

• DCs are isolated, cultured, and modified with tumor associated antigens to boost anti-tumor immunity.

Bacterial Vector

• Involves live bacteria, modified by attenuating bacterial toxicity and use to deliver heterologous antigens to the host immune systems.
• Potential benefits include reduced purification cost, but it may lead to anti-vector immunity in repeated therapies.

Viral Vector

• Uses harmless virus that encodes for pathogen antigen, enabling broad range application hence not restricted to a single type of infection.
• High effectiveness hence wide applicability but previous vector exposure can hinder its efficiency and it's not adequate for immunocompromised patients.

Toxoid Vaccine

• Utilizes inactivated bacterial toxins to activate immune responses, and it led to the first combination vaccines.
• Limited immunogenicity hence boosters are necessary to maintain effectiveness.

Nucleic Acid (mRNA, DNA) Vaccine

• Utilizes the genetic material of a pathogen, coding for antigenic proteins, to trigger immunity against pathogens without risks of disease acquisition in the patient, and efficient fast manufacturing, hence a widely applicable technology.
• mRNA degrades quickly which is a primary limitation making it unstable. Unwanted immune responses/side effects are also possible.

mRNA Vaccine Challenges

• Large mRNA molecules pose difficulties in transport.
• Currently, the use of lipid complexes and nanoparticles are used as delivery mechanisms to enhance stability and safety, and to reduce costs.
• Host immune system reactions, and impurities in mRNA necessitate purification techniques.

Future of mRNA Vaccines

• mRNA-based vaccines are being explored in prophylaxis against various diseases, including HIV, influenza, and chronic diseases like cancer.
• Some new viral vector types and antigens are being developed to target different disease.

Prophylactic and Therapeutic Cancer Vaccines

• Prophylactic vaccines target viral infections linked to cancer development.
• Therapeutic vaccines target cancer cells, typically to help the immune system recognize and eliminate them.
• Personalized cancer vaccines may use antigens from the patient's tumor to boost antigen-specific T cell responses against specific cancers.

Personalized Cancer Vaccines

• Personalized cancer vaccines use autologous tumor cells or tumor-derived products to elicit anti-tumor responses.
• Identification of neoantigens and tumor-associated antigens enhances the effectiveness of the anti-tumor response in the patient and helps eradicate tumors.

Future Perspectives

• New vaccine vectors, improved antigen delivery, overcoming immune suppression, enhancing antibody response, and development of new vaccines are needed to address unmet health needs.
• Focusing on prevention particularly in antibiotic-resistant bacteria are critical areas for vaccine development.

Requirements for an Effective Vaccine

• Effective vaccines must induce an adaptive immune response to protect a population against diseases caused by virulent pathogens.
• Vaccine safety and long-term effectiveness are paramount.
• The cost-effectiveness of delivery methods should also be considered.

Features of Therapeutic Biopharmaceuticals and Prophylactic Vaccines

• Comprehensive table outlining differences between therapeutic and preventative biopharmaceuticals regarding:
  • Target population
  • Acceptable risk-to-benefit ratio
  • Therapeutic doses
  • Number of doses
  • Need for combination/needle free delivery
  • Development time
  • Success rate
  • Main features bill of testing
  • Cost.