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VARICELLA VACCINE (Immunology Aspect (How vaccine is given? (Vaccine is…

- - - - :red_flag: Infection causes presence of fever constitutional symptoms, vesicular, and widely disseminated rash which involved trunk and face
        :red_flag: Minimal VZV to resolve is seven days, but could lead to severity if its more than ten days
      - :red_flag: Secondary infection could occur if the virus remains latent and reactivated in the nerve cells
        :red_flag: Secondary infection – known as herpes zoster or shingles that may results in permanent nerve damage
      - :red_flag: Acute Varicella occurred when it is exposed by direct contact with skin lesion or airborne spread from respiratory droplets
        :red_flag: Establish lifelong latency in cranial nerve, dorsal root ganglia, which could be reactive in years or decades, but evolved as herpes zoster or shingles
    - - :question: Direct Fluorescent Assay (DFA): Rapid method by using the scraping taken from the base of a skin lesion
        :question: Polymerase Chain Reaction (PCR): used to detect invasive disease, where VZV could be detected in vesicle fluid, serum, spinal fluid and other tissues
        :question: Viral culture: Help to distinguish VZV from other viral pathogens, specific but less sensitive as it give slow results
- - - - Derived from clade 2 wild-type virus pOka
      - 3 types of vaccine produced
        
        Biken
        
        :black_flag: Produced through passage of parents Oka virus (pOka) 11 times in human embryo fibroblast cells at 34°C, 12 times in guinea pig embryo fibroblast cells at 37°C, and a further three times in human WI-38 and MRC-5 cells
        
        Varivax
        
        Cloning of ORF 62 performed using TOPO XLPCR cloning kit with One Shot TOP10 chemically competent Escherichia coli (KA4750-10; Invitrogen) and suicide gene selection
        
        :black_flag: Produced by a further seven passages of vOka/Biken-infected cells in MRC-5 cells
        
        Varilrix
        
        :black_flag: Produced through a series of five limiting-dilution clonings using cell-free virus, resulting in a further 6 passages in W1-38 cells and 8 passages in MRC-5 cells
        
        :black_flag: Contain two fixed wild type alleles in ORF62 (positions 106710 and 107599) that are present as a mixture of wild type and vOka alleles in vOka/Biken and/or Varilrix
        
        Whole-genome sequencing of the 3 vaccine preparations and early analysis of vOka-associated SNPs were performed using direct Sanger sequencing
      - Complete DNA sequence of vOka revealed base substitution at 42 loci that clustered in the major viral gene transactivator protein encoded by open reading frame 62 (ORF 62)
        
        :fire: Most of the vOka-specific loci were determined to be mixtures of the wild-type and vOka nucleotides
        
        :fire: vOka is a heterogeneous population of viral strains.
        
        :fire: Three loci in ORF62, 106262, 107252, and 108111, are used to distinguish vOka from wild type virus
        
        :fire: Involve multiple mutations within both ORF 62 and several other genes
        
        :fire: Presence of wild-type allele is also likely to contribute to the immunogenicity and pathogenicity of the vaccine
        
        :fire: Single Nucleotide Polymorphism (SNP) profile of this virus provided no suggestion that recombination between vOka and a wt virus had occurred.
        
        :fire: ORF 62 is one of the immediate early gene
      - How the virus is attenuated
        
        :black_flag: By sequential passage in human embryonic lung cell culture, embryonic guinea pig fibroblasts, and in WI-38 human diploid cells which undergone further passage through MRC-5 human diploid cells cultures for a total of 31 passages