Designing antiviral vaccines for cytotoxic T cell (CD8+) activation Which vaccine formulation is most likely to elicit strong cytotoxic T lymphocyte responses?

Difficulty: Medium

Correct Answer: Live virus (attenuated) capable of intracellular replication

Explanation:


Introduction:
Cytotoxic T lymphocytes (CTLs, CD8+) recognize peptides presented on MHC class I, typically derived from endogenous proteins synthesized inside infected cells. Vaccine designs that place antigen in the cytosol efficiently prime CTLs.


Given Data / Assumptions:

  • MHC I presentation favors intracellularly produced antigens.
  • Live attenuated viruses replicate to limited degrees and generate endogenous antigen.
  • Inactivated or purely extracellular antigens mainly drive MHC II helper responses unless cross-presentation occurs.


Concept / Approach:

Live attenuated vaccines mimic natural infection, ensuring robust MHC I presentation and strong CTL memory. While cross-presentation can occur with certain adjuvants or delivery systems, it is less reliable than true intracellular synthesis.


Step-by-Step Solution:

1) Identify pathway: CTLs require peptide–MHC I derived from intracellular antigen.2) Select vaccine type that delivers antigen to the cytosol: live attenuated virus.3) Predict strong CD8+ priming with additional CD4+ help for optimal memory.4) Conclude live attenuated formulation is most consistent for robust CTL activation.


Verification / Alternative check:

Historically, live attenuated viral vaccines (where safe) generate durable cellular and humoral immunity, including CTL responses.


Why Other Options Are Wrong:

Option A: High dose inactivated virus favors antibody responses; CTL priming is limited without cross-presentation.

Option B: Adjuvants enhance innate signals but cannot substitute for antigen and proper presentation pathway.

Option D/E: Exogenous peptides/subunits may not reach MHC I efficiently unless specialized delivery or cross-presentation is ensured.


Common Pitfalls:

Assuming dose or adjuvant alone determines CTL responses; the intracellular location of antigen synthesis is the key determinant.


Final Answer:

Live virus (attenuated) capable of intracellular replication

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