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?

Difficulty: Easy

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).

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