Recombinant HBV vaccine platform — The genes encoding HBsAg for the Hepatitis B vaccine were cloned and expressed using which type of vector/host system to mass-produce the antigen?
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APlasmids (general bacterial expression, non-yeast)
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BCosmids (lambda-based high-capacity vectors)
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CAutonomously replicating plasmid of yeast (e.g., 2µ-based; expression in Saccharomyces cerevisiae)
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DPhagemids (phage–plasmid hybrids)
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EBaculovirus in insect cells as the primary licensed platform
Answer
Correct Answer: Autonomously replicating plasmid of yeast (e.g., 2µ-based; expression in Saccharomyces cerevisiae)
Explanation
Introduction / Context:The landmark Hepatitis B vaccine leverages recombinant expression of HBsAg in non-pathogenic hosts. Identifying the expression system clarifies why large-scale, safe production was feasible and consistent across global manufacturers.
Given Data / Assumptions:
- HBsAg forms self-assembling virus-like particles when expressed in certain systems.
- Yeast provides eukaryotic protein processing and scalable fermentation.
- Vector choice impacts copy number, stability, and yields.
Concept / Approach:Many licensed HBV vaccines express HBsAg in Saccharomyces cerevisiae using autonomously replicating yeast plasmids (often 2µ origin-based) under strong promoters. Yeast expression yields high titers of properly assembled HBsAg particles suitable for purification and formulation with alum adjuvant.
Step-by-Step Solution:
Clone HBsAg gene into yeast expression vector (2µ-based).Transform S. cerevisiae; select high-expressing clones.Ferment, harvest, and purify HBsAg particles.Formulate vaccine; confirm antigenicity and safety.Verification / Alternative check:Product monographs and WHO prequalification summaries describe yeast-derived HBsAg production platforms for multiple licensed vaccines.
Why Other Options Are Wrong:
- General bacterial plasmids: early attempts were less successful for VLP assembly compared to yeast.
- Cosmids/phagemids: not standard for licensed HBsAg vaccine production.
- Baculovirus/insect cells: used for some VLPs and proteins, but the classic HBV vaccines are yeast-based.
Common Pitfalls:Assuming all recombinant vaccines use bacterial expression; eukaryotic hosts often yield better assembly and post-translational features.
Final Answer:Autonomously replicating plasmid of yeast (e.g., 2µ-based; expression in Saccharomyces cerevisiae).