Larson Intro to Vaccines

What is the general purpose of vaccines?

To generate an immune response in the absence of a pathogen (or with a less pathogenic microbe)

Vaccines reduce risk of _____

Disease-associated complications and hospitalizations

What happens in the immune system when a vaccine is administered?

• Dendritic cells collect vaccine antigens and adjuvants

• Dendritic cells migrate to lymph nodes

• Antigens are presented to CD4 and CD8 T cells

• CD8 T cell activation results in CD8 effector T cells and CD8 memory T cells

• T cell help from activated CD4 T cells leads to:

  • additional activation of CD8 T cells

  • proliferation of antigen specific B cells

  • maturation of the antibody response

  • plasma cell differentiation and antibody production

  • proliferation of memory B cells

The immune memory after vaccination for a pathogen with a long incubation time (like Hepatitis B) is _____

sufficient

the antibodies will reach the necessary protective level without a booster vaccine

The immune memory after vaccination for a pathogen with a short incubation time (like Influenza B) is _____

not sufficient

rapidly invasive pathogens require boosters to produce a sufficient response

Live attenuated vaccines

Live pathogens that have been weakened or inactivated

Attenuation

Reduces virulence while maintaining immunogenicity

Rational attenuation

Inactivates or removes virulence genes by targeted mutations or gene deletion (typical for viruses)

Killed whole organism vaccines

Whole organism killed by physical or chemical means

Toxoid vaccines

modified bacterial exotoxins

How do toxoid vaccines work?

Antibodies directed at toxoid neutralize exotoxins before they reach the target cell

Why are antibodies effective at neutralizing exotoxins?

Antibodies recognize linear epitopes AND conformation epitopes

This includes secondary, tertiary, and quaternary protein structure, as well as glycosylated proteins

Subunit vaccines

Antigenic molecules or critical epitopes necessary for protection against infection

Whole cell vaccines contain nonantigenic molecules that can cause rare systemic and frequent local adverse effects

Purified protein, recombinant protein, polysaccharide, peptide

Virus-like particle vaccines

Particles constructed of viral proteins that structurally mimic the native virus but lack the viral genome

Nonenveloped VLPs or Enveloped VLPs

Outer membrane vesicle vaccines

Contain gram negative bacterial outer membrane and antigen

Polysaccharide and protein-polysaccharide conjugate vaccines

Need to be conjugated to proteins to elicit T cell dependent responses and generation of immune memory

Viral vectored vaccines

Recombinant virus (replicating or not) with altered genomes to express the target pathogen antigen

Nucleic acid vaccines

Consist of either DNA or RNA encoding the target antigen

Subcutaneous or intramuscular injection of vaccines

• Stimulates systemic immunity in the spleen, lymph nodes, and peripheral blood

• Interrupts person-to-person transmission

• Prevents the spread to crucial organs

Mucosal administration of vaccines

Antigen-stimulated lymphocytes from initial site travel to other mucosal surfaces conferring immunity at multiple mucosal sites

Passive protection

Use of specific neutralizing antibodies purified from immune donors to prevent the transmission of various viruses

Main point of herd immunity

For vaccine coverage above the threshold for herd immunity, infection cannot spread in the population and susceptible individuals are indirectly protected by vaccinated individuals

MMR vaccine

Live attenuated vaccine for measles, mumps, and rubella

(Other options include measles alone or in combination with mumps or rubella)