vaccines

Final Exam Information

  • Final exam on Wednesday, in class, paper format, from 11 AM to 12 PM.
  • Online final is available until the testing center closes on the 12th.
  • Pearson homework closes on the 12th at the end of the day.
  • Last iClicker quizzes are today.
  • Grades will be available after the 12th, likely worked on around the 13th.
  • Curves for Exam 3 will be calculated after the exam.
  • The testing center is open on the reading day and through the 13th.
  • The final exam will be 50 questions, with an hour (60 minutes) allotted, covering the last quarter of the material.

Vaccines: History and Types

  • First half of the period covers vaccines, followed by iClicker quiz reviews for Exam 4.
  • Vaccination history:
    • Ancient practices in China and the Middle East involved variolation, exposing children to smallpox pus to induce immunity.
    • Edward Jenner discovered that cowpox could provide immunity to smallpox.
    • Term "vaccination" honors Jenner's work.
    • Louis Pasteur developed vaccines for rabies and anthrax.
    • Robert Koch attempted to create a tuberculosis vaccine without success.
    • 1950s: Polio, measles, and mumps vaccines developed due to advancements in eukaryotic cell and tissue culture.
    • 1970s-80s: Recombinant DNA technology led to recombinant vaccines like the hepatitis B vaccine.
    • Newest generation: Messenger RNA (mRNA) vaccines.

Major Types of Vaccines

  • Not all vaccines are the same or accomplish the same thing.

1. Attenuated Whole Agent Vaccines

  • Example: Cowpox.
  • Considered the gold standard: Establishes infection, induces immunoglobulin and CTL responses.
  • Usually leads to a robust immune response.
  • Often makes the patient slightly sick, indicating a strong reaction to the vaccine.
    • Example: MMR vaccine in a three-year-old child can cause unpleasant symptoms for 48 hours.
  • Problem: Not all diseases can be made into safe attenuated vaccines (e.g., hepatitis C, HIV).
  • Risk of spreading the disease to susceptible populations (e.g., attenuated polio vaccine).

2. Inactivated Whole Agent Vaccines

  • Involves heating or chemically inactivating an agent to induce immunity.
  • Example: Original Salk polio vaccination.
  • Administered via injection rather than orally.
  • Easier to produce and eliminates the risk of transmitting the infectious agent.
  • Problem: Heating or chemical inactivation can destroy immunogenicity, leading to poor and short-lived immunity.

3. Toxoid Vaccines

  • Vaccinate against a toxoid (toxin) rather than the agent itself.
  • Historically, vaccines were primarily against viral infections until toxoids were developed.
  • Example: Tetanus vaccine.
  • Vaccinates against the tetanus toxin produced by Clostridium tetani.
  • Boosters are required to maintain circulating antibodies against the tetanus toxoid.

4. Subunit Vaccines

  • Developed using modern biotechnology.
  • Example: Hepatitis B vaccine.
  • Involves taking the most immunogenic part of the virus (e.g., envelope protein of HBV).
  • The protein is expressed and purified from yeast cells.
  • The properly folded protein is administered as a vaccine.

5. Nucleic Acid Vaccines (mRNA)

  • Newest generation of vaccines.
  • Early focus on DNA vaccines faced issues related to recombination in target cells.
  • RNA vaccines offer a good alternative.
  • Challenge: RNA degrades quickly.
  • mRNA vaccines must be stored at very low temperatures (e.g., -70 degrees Celsius).
  • Issues with storage and handling may affect effectiveness.
  • Benefits: Rapid development, allowing for quick response to new pandemics; a vaccine can be developed in literally a month.

6. Conjugated Vaccines

  • Administering multiple vaccines together (e.g., DTaP, MMR).
  • Leads to a greater inflammatory response, T helper cell response, and proliferation of memory T and B cells.
  • Reduces the number of shots required.
  • MMR requires three doses; administering separately increases pediatric visits and shots.
  • Administering all childhood vaccinations separately may involve as many as 72 shots by age 12.
  • Offers socioeconomic benefits by reducing pediatric visits.
  • Examples of vaccines include attenuated (MMR) and inactivated (rabies, Salk polio, DTaP).
  • Diphtheria and tetanus toxoids (in DTaP) target exotoxins.
  • Subunit vaccines allow for effective vaccines against bacterial infections (e.g., HIB, streptococcal pneumoniae, hepatitis B).
  • No fungal or protozoan vaccines exist in normal vaccination series due to antigenic diversity.

7. Messenger RNA (mRNA) Vaccines

  • Examples: Moderna, Pfizer.
  • mRNA doesn't recombine with DNA and has a short half-life in the body.
  • Produces the protein, which is properly folded.
  • Rapid synthetic production possible once the sequence of the infectious agent is known.
  • The turnover possibility of messenger RNA-based vaccines is very fast.
  • Problem: Doesn't last long and may not generate as robust of an immune response as attenuated whole-agent vaccines.
  • DNA-based vaccines were less successful and carried the risk of DNA incorporation into the host genome.

Reasons for Lack of Vaccines Against Everything

  • Some agents are not very immunogenic (e.g., HIV).

  • Enveloped viruses like HIV have envelope proteins that don't stick out much until they meet the receptor (CD4).

  • Developing even a 95% effective vaccine against HIV may not be practical due to ongoing risk.

  • Difficulties in culturing some organisms (e.g., hepatitis C).

  • Some agents, despite recombinant DNA attempts, do not confer lasting effective immunity.

  • Therapeutic index considerations (risk vs. benefit).

  • Cost of developing and administering vaccines is high, especially for sporadically occurring diseases like Ebola.

    • Legal risks and liability associated with pharmaceutical agents.

Risks Associated with Vaccination

  • Guillain-Barré syndrome:
    • Peripheral autoimmune condition linked to infections and, potentially, vaccinations.
  • Tumors in cats:
    • Observed with a rabies vaccine due to an adjuvant agent; this vaccine is no longer on the market.
  • Legal issues related to autism:
    • Concerns about liability for autism, which is a falsehood.
  • Potential for attenuated polio vaccine to infect unvaccinated individuals.
  • Mild myocarditis:
    • Associated with RNA-based coronavirus vaccines.
    • More related to widespread vaccination and pre-existing heart problems in middle-aged men.
    • Risk is lower with vaccination compared to getting the actual infection.

Association Between Autism and Vaccines

  • Autism diagnosis:

    • Didn't exist until the 1980s and the DSM listing.
    • Increase in diagnoses is partly due to better recognition.
    • Prior to 1980, children with autism may have been diagnosed with pediatric schizophrenia or warehoused in state mental hospitals.

  • Department of Education's role:

    • Founded to provide equitable funding for schools and support special needs children mainstreamed into schools.
    • Shifted healthcare costs from Health and Human Services to the Department of Education.

  • Incidence of autism:

    • Seems to be increasing beyond just diagnosis and recognition.

    • Older pediatricians note a rise in spectrum cases.

    • Doesn't correlate with vaccination timelines.

      • Parent's perception:
        • Association often arises because vaccinations occur during pediatric visits where developmental concerns are first raised.
        • Denmark studies show no statistically significant difference in autism rates between vaccinated and unvaccinated children.
        • Some studies even suggest a slightly increased risk of autism in unvaccinated children.

Vaccine Side Effects and Compensation

  • Real risk of vaccination is anaphylaxis or contaminated vials.
  • Risk of severe injury from vaccination is between one in a million to one in three million.
  • Mild side effects include pain or inflammation at the injection site.
  • The link between coronavirus vaccines and women's menstrual cycles is plausible but not necessarily medically significant.
  • The success of vaccination in reducing infant mortality is significant.
  • Risks associated with natural infections are higher than vaccination risks.
  • Measles deaths are preventable through vaccination, and the cumulative effect on a national scale is significant.

Review Quizzes

  • Human papillomavirus (HPV) causes cervical cancer in women and throat cancer in men.
  • Prions are proteinaceous infectious agents involved in diseases like mad cow disease.
  • Hepatitis D (delta agent) can only replicate along with Hepatitis B and is very deadly.
  • Rabies virus can be vaccinated after exposure due to its slow-moving infection.
  • The prevalence of HIV is decreasing due to education, awareness, pre-exposure prophylaxis, and treatment therapies, not vaccination.
  • Classical pathway of complement activation requires antibodies (IgG or IgM) plus C1.
  • Interferon gamma, produced by helper T cells, is a broad immune system activator.
  • Tachycardia (accelerated heart rate) is a deleterious aspect of fever.
  • IgE associates with mast cells.
  • Bacteria using the CRISPR system can capture bacteriophage antigens; humans do not do this.
  • Immunoglobulin gene rearrangement contributes to the enormous antibody diversity; humans do not have millions of immunoglobulin genes.