🦠Virology Unit 16 – Viral Vaccines and Prevention Strategies

Introduction to Viral Vaccines

• Viral vaccines are biological preparations that provide active acquired immunity against specific viral diseases
• Contain either inactivated virus, live attenuated virus, viral proteins, or genetic material (DNA or RNA) encoding viral proteins
• First successful viral vaccine developed by Edward Jenner in 1796 for smallpox using cowpox virus
• Have greatly reduced the burden of many viral diseases worldwide (polio, measles, rubella, mumps)
• Herd immunity occurs when a significant portion of a population is vaccinated, reducing the likelihood of disease spread
• Vaccines not only protect individuals but also limit the spread of viruses within communities
• Some vaccines require multiple doses or booster shots to maintain immunity over time
• Vaccine efficacy refers to the percentage reduction of disease in a vaccinated group compared to an unvaccinated group

Types of Vaccines

• Live attenuated vaccines use weakened viruses that can still replicate but do not cause severe disease (measles, mumps, rubella, varicella)
  • Induce strong and long-lasting immune responses but may not be suitable for immunocompromised individuals
• Inactivated vaccines use viruses killed by heat or chemicals, unable to replicate but still stimulate an immune response (polio, hepatitis A, rabies)
  • Generally safer but may require multiple doses for optimal protection
• Subunit vaccines use specific viral proteins or peptides to elicit an immune response (hepatitis B, human papillomavirus)
  • Highly specific and safe but may have lower immunogenicity compared to whole virus vaccines
• Conjugate vaccines link a weak antigen to a strong antigen to enhance the immune response (Haemophilus influenzae type b)
• Toxoid vaccines use inactivated bacterial toxins (diphtheria, tetanus)
• Nucleic acid vaccines deliver DNA or RNA encoding viral proteins into host cells for antigen production (experimental COVID-19 vaccines)
  • Potentially faster and cheaper to produce but still a relatively new technology
• Viral vector vaccines use a harmless virus to deliver genetic material encoding target viral proteins (Ebola, experimental COVID-19 vaccines)

How Vaccines Work

• Vaccines work by exposing the immune system to viral antigens without causing disease, triggering an adaptive immune response
• Antigen-presenting cells (dendritic cells, macrophages) process and present viral antigens to T lymphocytes
  • Major histocompatibility complex (MHC) molecules present antigens to T cells
• B lymphocytes produce antibodies specific to viral antigens, neutralizing viruses and marking them for destruction
  • Antibodies can block viral entry into cells, facilitate phagocytosis, and activate complement system
• T lymphocytes differentiate into cytotoxic T cells that directly kill virus-infected cells and helper T cells that support antibody production
• Memory B and T cells persist after vaccination, providing rapid and enhanced response upon subsequent exposure to the virus
• Vaccines may contain adjuvants (aluminum salts, oil-in-water emulsions) that enhance the immune response by stimulating innate immunity
• Route of administration (intramuscular, subcutaneous, oral) can affect the type and strength of the immune response
• Duration of immunity varies depending on the vaccine and the individual, ranging from months to lifelong protection

Vaccine Development Process

• Vaccine development is a complex, multi-stage process that can take many years and significant financial investment
• Basic research identifies potential viral antigens and understands the virus's structure, life cycle, and pathogenesis
• Preclinical studies evaluate vaccine candidates in animal models for safety, immunogenicity, and efficacy
  • Assess different vaccine platforms, adjuvants, and routes of administration
• Clinical trials involve human volunteers and progress through three phases:
  • Phase 1: Small groups (20-100) of healthy volunteers to assess safety and immunogenicity
  • Phase 2: Larger groups (hundreds) to further evaluate safety and determine optimal dose and schedule
  • Phase 3: Large-scale trials (thousands) to confirm efficacy and monitor for rare adverse events
• Regulatory review by agencies (FDA, EMA) to ensure safety and efficacy before approval and licensure
• Post-licensure surveillance monitors for rare adverse events and long-term effectiveness in the general population
• Vaccine production requires strict quality control and adherence to good manufacturing practices (GMP)
  • Ensuring consistency, potency, and purity of each vaccine batch
• Accelerated vaccine development may occur during public health emergencies (COVID-19 pandemic) through parallel testing and regulatory fast-tracking

Key Viral Vaccines and Their Impact

• Smallpox vaccine: First successful vaccine, led to global eradication of smallpox in 1980
• Polio vaccines (inactivated and oral): Global polio cases reduced by 99% since 1988, eradication efforts ongoing
• Measles vaccine: Measles deaths reduced by 73% worldwide between 2000-2018, but outbreaks still occur in under-vaccinated populations
• Rubella vaccine: Congenital rubella syndrome prevented, rubella eliminated from the Americas in 2015
• Hepatitis B vaccine: Dramatic reduction in chronic hepatitis B and liver cancer, especially when given at birth
• Human papillomavirus (HPV) vaccine: Significant decrease in HPV infections and cervical precancers, expected to reduce cervical cancer rates
• Influenza vaccines: Annually updated to match circulating strains, reduce severity and mortality, especially in high-risk groups
• Rotavirus vaccines: Substantial decline in hospitalizations and deaths from rotavirus diarrhea in young children
• Varicella (chickenpox) vaccine: Decreased incidence and complications, including pneumonia and encephalitis
• Zoster (shingles) vaccine: Reduced risk and severity of shingles in older adults

Challenges in Vaccine Development

• Antigenic variation in some viruses (influenza, HIV) requires frequent vaccine updates or hinders vaccine development
• Limited understanding of correlates of protection for some viruses, making it difficult to assess vaccine efficacy
• Inadequate animal models that do not fully replicate human disease or immune responses
• Difficulty in inducing broadly neutralizing antibodies against highly variable viruses (HIV, hepatitis C)
• Safety concerns, especially for live attenuated vaccines in immunocompromised individuals
• Ensuring vaccine stability and cold chain maintenance, particularly in resource-limited settings
• Overcoming vaccine hesitancy and misinformation, which can lead to decreased vaccine uptake and herd immunity
• Equitable global access to vaccines, with disparities between high-income and low- and middle-income countries
• Balancing speed and safety in accelerated vaccine development during public health emergencies
• Addressing rare but serious adverse events (vaccine-associated paralytic poliomyelitis, Guillain-Barré syndrome)

Prevention Strategies Beyond Vaccines

• Antiviral drugs can prevent or treat viral infections, but are specific to certain viruses and may have side effects
  • Pre-exposure prophylaxis (PrEP) for HIV, oseltamivir for influenza
• Passive immunization with antibodies (convalescent plasma, monoclonal antibodies) can provide temporary protection or treatment
• Vector control measures to reduce the population of mosquitoes, ticks, or other arthropods that transmit viruses
  • Insecticide-treated bed nets, indoor residual spraying for malaria prevention
• Safe food and water practices to prevent foodborne and waterborne viral illnesses (norovirus, hepatitis A)
  • Proper hand hygiene, food preparation, and water treatment
• Blood and organ donor screening to prevent transfusion- or transplantation-transmitted viral infections (HIV, hepatitis B and C)
• Safer sex practices, including condom use and partner reduction, to prevent sexually transmitted viral infections (HIV, HPV, hepatitis B)
• Harm reduction strategies for people who inject drugs, such as needle and syringe exchange programs, to reduce the risk of blood-borne viruses (HIV, hepatitis C)
• Infection control measures in healthcare settings to prevent nosocomial viral transmission
  • Personal protective equipment (PPE), hand hygiene, isolation precautions

Future Trends in Viral Vaccine Research

• Rational vaccine design based on structural biology and computational modeling to identify optimal antigens and adjuvants
• Nucleic acid vaccines (DNA, mRNA) offer potential for rapid development, flexibility, and scalability
  • mRNA vaccines have shown promise in the COVID-19 pandemic
• Viral vector vaccines, using adenoviruses or other harmless viruses, to deliver target antigens
• Nanoparticle-based vaccines to enhance antigen stability, delivery, and immunogenicity
• Adjuvant development to improve vaccine efficacy and enable dose-sparing
  • Novel adjuvants such as TLR agonists, saponins, and combination adjuvants
• Mucosal vaccines (oral, intranasal) to induce local immunity at the site of viral entry
  • Potential for needle-free administration and improved compliance
• Therapeutic vaccines to treat chronic viral infections or virus-associated cancers (HIV, HPV, hepatitis B)
• Personalized vaccines based on an individual's genetic and immunological profile
• Improved vaccine thermostability and cold chain-independent formulations for easier global distribution
• Vaccine platforms for rapid response to emerging viral threats, as demonstrated during the COVID-19 pandemic