Vaccines + Immunity: Introduction

vaccines generate an immune response when…

absence of pathogen or less pathogenic microbe

immune memory is sufficient when…

incubation period is long

immune memory may NOT be sufficient when…

against rapidly invasive pathogens

live attenuated vaccine - attenuation

reduces virulence while maintaining immunogenicity (causes disease but still able to stimulate immune response)

attenuation is done by…

• pass through unnatural host

• grow on unusual media

• expose to harsh chemicals for extended periods

  • lose critical genes necessary for virulence factors

live attenuated vaccine - rational attenuation

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

ex. BCG

killed whole organism vaccine

• whole organism killed by physical or chemical means

  ex. salk polio (i.m. or s.c.)

toxoid vaccine

• antibodies directed at toxoid neutralize exotoxins before they reach target cell

toxoid vaccine - antibodies effective at neutralizing exotoxins

• antibodies recognize linear epitopes AND conformational epitotes

  • 2°, 3°, 4° protein structures

  • even glycosylated proteins too

subunit vaccine

antigenic molecules or critical epitopes necessary for protection against infection

virus-like particle vaccine

• particles constructed of viral proteins that structurally mimic native virus but lack viral genome

  • nonenveloped VLPs

  • enveloped VLPs

    ex. Gardasil for Human Papillomarvirus

outer membrane vesicle vaccine

• gram-negative bacterial outer membrane + antigen

• contain PAMPs —> activation Toll-like receptors (TLRs)

  ex. Group B meningoccocal

polysaccharide + protein-polysaccharide conjugate vaccines

polysaccharide needs to be conjugated to proteins to elicit T cell-dependent responses + generation of immune memory

newer platforms: viral vectored vaccine

• recombinant virus (replicating or not) w/ alter genomes to express target pathogen antigen

  ex. AstraZeneca COVID-19 adenovirus vector vaccine (AZD1222)

newer platforms: nucleic acid vaccine

• consist of either DNA or RNA encoding target antigen

• requires uptake of nucleic acid by vaccine recipient cells

2 ways Type I interferons (IFNs) help fight virus

1) activate nucleases - cleave viral RNA

2) inhibit viral protein synthesis - downregulating protein elongation factors