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#live attenuated vaccines

3 public questions tagged with this topic.

Vaccine

Live attenuated vaccines are weakened by:

Live attenuated vaccines are weakened by serial passaging in non natural host cell cultures, tissues or under suboptimal temperature forcing accumulation of adaptive mutations and deletion of virulence genes. Method pioneered by Louis Pasteur for anthrax and rabies via passage in animals. For viral vaccines, poliovirus Sabin strains passaged in monkey kidney and mouse spinal cord selecting neurovirulence attenuating mutations in 5'UTR internal ribosome entry site reducing replication in neurons while retaining replication in gut. Measles Edmonston strain passaged in primary human kidney cells,

Ref: Pasteur attenuation principle; Plotkin live vaccine passage; WHO Live attenuated methods.

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Immunological Applications

Live attenuated vaccines differ from inactivated vaccines because they:

Live attenuated vaccines developed through classical virology approach reducing pathogenicity while retaining replicative capacity that mimics natural infection without causing severe disease. Attenuation strategies include serial passage in heterologous host cells like chick embryo fibroblasts, embryonated eggs, or at subphysiologic temperature 25 to 33 degrees cold adaptation accumulating adaptive mutations in polymerase genes L and P reducing transcription efficiency in human cells at 37 degrees, plus mutations in surface glycoprotein cleavage sites reducing fusogenicity and in interferon a

Ref: Plotkin Vaccines 7th ed live attenuated replication PAMP; Abbas Cellular Molecular Immunology Sabin polio reversion risk.

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Immunological Applications

Live attenuated vaccines differ from inactivated vaccines because they:

Live attenuated vaccines comprise pathogens weakened laboratory passage serial passage heterologous hosts chick embryo fibroblasts 100 times cold adaptation growth 25C restrictive temperature-sensitive polymerase mutations or targeted deletions removing virulence determinants NS1 influenza inhibiting interferon thymidine kinase herpes limiting replication neurons capsule genes retaining ability infect host cells particularly epithelial dendritic cells transcribe viral genes under cellular Pol II produce antigens near wild-type assemble virions replicate transiently low levels limited host inna

Ref: Plotkin Vaccines 8th ed Live Attenuated vs Inactivated Comparison; CDC Vaccine Types Replication Immunity Mechanisms; Janeway Live Vaccine Cellular MHC I Chapter 12.

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