Vaccines

• Variolation - inoculation of smallpox into the skin

  • Origins: China → Middle east → Europe

  • Supplying the infectious agent in some form to the host to produce an immune system response

Edward Jenner inoculated cowpox to prevent smallpox (cross-reaction)

• Termed vaccination by Pasteur (vacca = cow)

• If certain diseases have similar antigens (i.e. smallpox and cowpox), your body can still produce similar responses to each one. If you gain immunity to cowpox, your body will likely be able to fight off smallpox as well. This is cross-reaction.

Vaccine - suspension of organisms or fractions of organisms that induce immunity

Vaccines provoke a primary immune response; formation of antibodies and memory cells

• Booster dose produces a rapid, intense secondary response

Herd immunity - immunity in most of the population

• Outbreaks are sporadic due to the lack of susceptible individuals

Types of Vaccines and Their Characteristics

• Live attenuated vaccines

  • Closely mimic the actual infection the pathogen produces because it’s live but weakened

  • Weakened pathogen, with reduced virulence, retains all of its antigenic properties

  • Preparation: mutate virulence genes; maintain virus in cell culture or non-human host

  • Closely mimic an actual infection

  • Confers lifelong cellular and humoral immunity

  • Infects hosts cells because it’s live but since because it’s weakened it can easily be killed off by our immune system

• Inactivated killed vaccines

  • Safer than live vaccines

  • Require repeated booster doses

  • Induce mostly humoral immunity

  • Does not infect host cells

• Subunit vaccines

  • Use antigenic fragments to stimulate an immune response

  • Recombinant vaccines: subunit vaccines produced by genetic modifications

    • Protein on the pathogen’s surface or a gene from the pathogen is taken and inserted into another organism such as a bacterial cell. The bacterial cell expresses it and makes more of the gene or protein. The protein can then be used to for the vaccine

  • DNA/RNA vaccines

    • Provides the genes for the antigen in a DNA and the DNA is injected into a human or organism and the cells of the host can take up that DNA

  • Recombinant vector vaccines

    • Uses a benign viral type that will contain DNA that has the antigen for the pathogen

    • viral type is avirulent so it will not cause any diseases

    • Virus-like particle (VLP) vaccines - resemble intact viruses but do not contain viral genetic material (HPV)

  • Toxoids - inactivated toxins

  • Virus-like particles (V L P) vaccines - resemble intact viruses but do not contain viral genetic material (HPV vaccine)

• Polysaccharide vaccines - made from molecules in pathogen’s capsule; not very immunogenic

  • Meningococcal vaccine & Pneumococcal vaccine

• Conjugated vaccines - used for disease in children with poor immune response to capsular polysaccharides

  • Link polysaccharide to protein → produces stronger immune response

• Nucleic Acid (DNA) vaccines

  • Naked DNA is injected into recipient cells & produces the protein antigen encoded in the DNA

  • Stimulates humoral and cellular immunity

• Recombinant vector vaccines

  • Use avirulent viruses or bacteria as delivery systems or vectors to deliver genes coding for antigens

  • Vectors are genetically modified

Pfizer/Moderna vaccine:

• Nucleic acid vaccine

• Used RNA vaccine

• The mRNA encodes an optimized SARS-CoV-2 full length spike glycoprotein (s), which is the target of neutralizing antibodies that are believed to inactivate the virus

Lipid Nanoparticles (LNPs) - encapsulates mRNA in lipid nanoparticles or LNPs

J&J vaccine

• Viral vector vaccine

• Recombinant Viral vector

• Based on a specific type of adenovirus that has been genetically modified so that it can no longer replicate in humans and cause disease

Vaccine Production, Delivery, and Formulations

• Oral vaccines preferred

• Skin patch: delivers dry vaccine; skin has abundance of antigen-presenting cells (Eliminates needles, simplified process)

• Multiple combination vaccines: reduce the number of injections

• Adjuvants: chemical additives that enhance effectiveness of vaccine

• Reverse Vaccinology

  • A pathogen’s DNA is scanned to find proteins that are likely to be on the cell’s surface. They ensure that the protein is unique to the pathogen and would likely trigger a strong immune response. These proteins are then tested on cells or animals to check if they provide immunity to the pathogen before being used to create the vaccine for the disease.

Vaccine Safety

• On rare occasions, vaccines can cause the disease.

• May have minor side effects: tenderness at the injection site, headache, fever, mild rash, and fatigue

• No medical or scientific proof of MMR vaccines being linked to autism

• Safest and most effective means of preventing infectious disease in children

• The health immunization campaigns saved millions of lives, e.g., Diphtheria vaccine

  • Before the vaccine: over 15,000 Americans died in 1921 alone

  • After the vaccine: only a single case reported to CDC since 2003

Use of Monoclonal Antibodies

• Monoclonal antibodies are B cells that are fused with myeloma cells (cancer cells) in order to prolong the B cells life because myeloma cells are characterized with uncontrolled growth

• Hybridoma - “immortal” cancerous B cells combined with an antibody producing normal B cell

  • Hybridoma produces monoclonal antibodies (MABS)

• Mabs are uniform, highly specific, and produced in large quantities

  • Used in diagnostic tools

  • Used in human therapy

  • Often derived from mouse cells; can have side effects

• Chimeric Mabs - mouse variable region + human constant region

• Humanized antibodies - 90% human + mouse antigen-binding sites

• Fully human antibodies - produced from a human gene in a mouse

  • Adalimumab (Humira) - to treat arthritis, psoriasis, Crohn’s disease

Precipitation Reactions

• Reaction of soluble antigens with IgG or IgM Abs to form large aggregates called lattices

  • Antigen-antibody complex forms, followed by the formation of a lattice that precipitates from the solution

  • Soluble antigens bind antibodies

• Precipitin ring test - a cloudy line forms where there is the optimal ratio of antigen and antibody

Agglutination Reactions

• Particulate antigens binding to antibodies to form visible aggregates

• Direct agglutination tests

  • Detect antibodies against large cellular antigens

  • Measure concentration of serum antibody (titer)

  • Rise in titer indicates a greater immunity to disease

• Indirect (passive) agglutination tests

  • Antibody reacts with the soluble antigen adhering to the particles or vice versa

  • adhering antigen to latex beads or coating the latex beads with the antigen. Patient serum is then mixed with these beads containing antibodies. You look for agglutination or clumping to occur. This test can be done conversely if looking for antigens with the beads coated in antibodies.

• Hemagglutination - agglutination of RBC surface antigens and complementary antibodies; used in blood typing