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#vaccine development

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, chick embryo fibroblasts adaptation to avian receptors reducing human pathogenicity. BCG created by 230 serial passages of Mycobacterium bovis on potato bile glycerin medium 1908-1921 resulting loss of RD1 region encoding ESX-1 secretion system essential for virulence. Alternative modern strategies include cold adaptation growing influenza at 25°C selecting viruses replicating in cooler upper respiratory tract not warm lower lung, generation of reassortants, or reverse genetics deleting virulence genes like HSV ICP34.5. Attenuated microbe replicates limitedly presenting native antigens via both MHC pathways, inducing strong cellular immunity. Reversion monitored by sequencing.

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

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Vaccine

Edward Jenner used material from which disease to immunize against smallpox?

Edward Jenner utilized material from cowpox, a mild zoonotic orthopoxvirus infection naturally occurring in cattle, to immunize against smallpox. Cowpox virus causes vesicular lesions on teats and udders of cows, transmitted via hands of milkers producing localized pustules on hands, mild fever and regional lymphadenopathy but self-limited disease due to limited replication in human skin. Jenner reasoned that cross-reactive antigens shared within Orthopoxvirus genus provide cross protection, since orthopoxviruses possess conserved envelope proteins like A27, H3, D8 and B5. In May 1796 he collected exudate from cowpox lesion on dairymaid Sarah Nelmes whose infection traced to cow Blossom, inoculated via two superficial incisions into arm of eight-year-old James Phipps, producing mild local lesion and fever resolving. Six weeks later challenged with smallpox pus via variolation and observed no disease, repeating challenge months later. This heterologous immunization approach safer than variolation because cowpox rarely caused systemic disease. Observations derived from folklore among milkmaids stating they could not take smallpox after cowpox. Cowpox remains basis of vaccinia vaccine strain used today although modern vaccinia may be derived from horsepox lineage distinct.

Ref: Jenner Inquiry 1798 cowpox; Baxby 1999 Cowpox to Vaccinia; Barquet Domingo Clin Microbiol.

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Animal Tissue Culture 3

Vero cells originate from:

Vero cell line originates from kidney epithelial tissue excised from adult African green monkey Chlorocebus aethiops, formerly Cercopithecus aethiops, at Chiba University Japan in 1962 by Yasumura and Kawakita. Designation Vero derived from Esperanto phrase Verda Reno meaning green kidney. Cells exhibit epithelial-like cobblestone morphology, anchorage dependence, contact inhibition, and were initially diploid but later became aneuploid after continuous passage. Critical molecular feature is homozygous deletion of approximately 9 megabase region on chromosome 12 encoding type I interferon gene cluster including IFNA and IFNB, disabling interferonbeta production and interferonstimulated gene response to viral infection. This interferon deficiency renders Vero highly permissive to wide range of viruses including poliovirus, measles, rabies, and SARS coronavirus while lacking adventitious retroviruses. Sublineages such as Vero E6 express high levels of ACE2 receptor facilitating SARS-CoV-2 isolation, and Vero 76 useful for hemorrhagic fever viruses. WHO endorsed Vero for vaccine manufacture due to safety profile. Authentication of Vero sublineages via genome sequencing prevents misidentification affecting vaccine lot consistency. This knowledge strengthens laboratory safety, protocol reproducibility, and regulatory compliance critical for translational research and clinical applications, ensuring reliable data and workforce protection.

Ref: Yasumura Y & Kawakita Y Nippon Rinsho 1963 Vero African green monkey kidney; Desmyter et al J Virol 1968 Interferon deficiency in Vero.

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