Single-shot vaccines MCQs With Answer are designed to help M. Pharm students consolidate core concepts in controlled-release immunization. Single-shot, or self-boosting, vaccines aim to deliver both priming and booster exposures from a single administration by embedding antigens and adjuvants within long-acting depots such as PLGA microspheres, polyanhydride matrices, implants, or microneedle patches. These systems depend on precise control of polymer chemistry, particle engineering, antigen stabilization, and immunological kinetics to mimic multi-dose schedules. The following MCQs probe formulation strategies, polymer degradation, release models, excipient choices, adjuvant compatibility, sterilization, thermostability, and in vitro–in vivo correlations. Work through them to strengthen your grasp of design trade-offs and translational challenges unique to single-shot vaccine delivery.
Q1. Which statement best defines a single-shot (self-boosting) vaccine in drug delivery terms?
- A vaccine requiring only a small needle for injection
- A formulation that induces immunity within 24 hours
- A system that delivers both priming and booster antigen exposures from one administration via controlled release
- A vaccine that contains multiple antigens for different pathogens
Correct Answer: A system that delivers both priming and booster antigen exposures from one administration via controlled release
Q2. The most widely studied biodegradable polymer for single-shot vaccine microspheres is:
- Polylactic-co-glycolic acid (PLGA)
- Poly(ethylene imine) (PEI)
- Poly(ethylene glycol) (PEG)
- Poly(N-isopropylacrylamide) (PNIPAM)
Correct Answer: Polylactic-co-glycolic acid (PLGA)
Q3. Increasing the lactide content (higher lactic:glycolic ratio) in PLGA generally results in:
- Faster water uptake and faster degradation
- Slower water uptake and slower degradation
- No change in degradation rate
- Immediate burst erosion regardless of molecular weight
Correct Answer: Slower water uptake and slower degradation
Q4. Which end-group modification in PLGA most helps reduce acidic microclimate and slow degradation?
- Acid-terminated PLGA
- Ester-capped PLGA
- Amino-terminated PLGA
- Hydroxyl-terminated PEG-PLGA block copolymer
Correct Answer: Ester-capped PLGA
Q5. The most suitable strategy to achieve a pulsatile “booster” release at ~4 weeks is to:
- Use a single population of low molecular weight PLGA microspheres
- Blend microsphere populations with different PLGA molecular weights and lactic:glycolic ratios
- Increase trehalose loading only
- Coat microspheres with alum adjuvant
Correct Answer: Blend microsphere populations with different PLGA molecular weights and lactic:glycolic ratios
Q6. Which approach best minimizes initial burst release of antigen from PLGA microspheres?
- Using highly porous particles with large surface area
- Core–shell microspheres with a dense, low-porosity shell
- Reducing polymer molecular weight
- Storing particles in aqueous buffer before injection
Correct Answer: Core–shell microspheres with a dense, low-porosity shell
Q7. A key limitation for protein antigens in PLGA depots is microclimate acidification during degradation. Which excipient most directly mitigates this?
- Trehalose
- Magnesium hydroxide (Mg(OH)2)
- Polysorbate 80
- Polyvinyl alcohol (PVA)
Correct Answer: Magnesium hydroxide (Mg(OH)2)
Q8. Which release pattern is most typical for PLGA-based single-shot depots in vivo?
- Pure zero-order release throughout
- Triphasic: initial burst, diffusion-controlled phase, then erosion-accelerated release
- Immediate complete release within 24 hours
- Biphasic: only diffusion and no erosion
Correct Answer: Triphasic: initial burst, diffusion-controlled phase, then erosion-accelerated release
Q9. Which adjuvant is most compatible for co-encapsulation in hydrophobic depots to drive a Th1-biased response?
- Aluminum hydroxide (alum)
- Monophosphoryl lipid A (MPLA)
- Squalene alone
- Phenol preservative
Correct Answer: Monophosphoryl lipid A (MPLA)
Q10. For a planar diffusion-controlled matrix, which model best describes early-time release?
- Higuchi model
- Michaelis–Menten model
- Langmuir isotherm
- Zero-order pump model
Correct Answer: Higuchi model
Q11. Which statement about microneedle-based single-shot vaccines is most accurate?
- They cannot create sustained release in skin
- They can embed antigen-loaded depots in the dermis for extended presentation to APCs
- They are limited to DNA vaccines only
- They require cold-chain at liquid nitrogen temperatures
Correct Answer: They can embed antigen-loaded depots in the dermis for extended presentation to APCs
Q12. Which sterilization strategy is generally preferred for PLGA microsphere vaccines to avoid polymer and antigen damage?
- Terminal gamma irradiation of the filled vial
- Ethylene oxide sterilization of final product
- Aseptic manufacturing of microspheres without terminal sterilization
- Autoclaving the microsphere suspension
Correct Answer: Aseptic manufacturing of microspheres without terminal sterilization
Q13. To enhance thermostability of proteins in single-shot depots, a common and effective approach is to:
- Increase residual solvent in particles
- Embed antigens in a sugar glass using trehalose or sucrose
- Use only hydrophobic peptides as antigens
- Store at high humidity to prevent drying
Correct Answer: Embed antigens in a sugar glass using trehalose or sucrose
Q14. Which release profile most closely aligns with robust germinal center responses and affinity maturation for many protein antigens?
- Large initial burst with no subsequent release
- Very slow release starting after 8–10 weeks
- Moderate priming burst followed by sustained low-level release over 2–4 weeks
- Daily oscillating pulses every 12 hours
Correct Answer: Moderate priming burst followed by sustained low-level release over 2–4 weeks
Q15. A single-shot vaccine requires a 50 µg antigen dose. If microspheres have 10% (w/w) antigen loading, what mass of microspheres is needed?
- 50 µg
- 100 µg
- 500 µg
- 5 mg
Correct Answer: 500 µg
Q16. Which is a key challenge for developing single-shot mRNA vaccines using PLGA depots?
- Excessive stability of mRNA at acidic pH
- Nuclease degradation and loss of activity during prolonged release
- Lack of innate immune activation by mRNA
- Inability to encapsulate any polyanion in polymers
Correct Answer: Nuclease degradation and loss of activity during prolonged release
Q17. Which polymer class is predominantly surface-eroding and can approximate zero-order release, benefiting single-shot profiles?
- Polyanhydrides
- PLGA
- Poly(ethylene carbonate)
- Poly(2-oxazoline)
Correct Answer: Polyanhydrides
Q18. Which strategy best reduces antigen adsorption to the water–oil interface during W/O/W microencapsulation?
- Adding interfacial stabilizers like polysorbate 80 and including sugar glass in the inner aqueous phase
- Increasing homogenization speed indefinitely
- Using organic solvent with higher polarity only
- Skipping the inner aqueous phase
Correct Answer: Adding interfacial stabilizers like polysorbate 80 and including sugar glass in the inner aqueous phase
Q19. For batch release of a single-shot vaccine, which in vitro quality attribute is most critical to correlate with clinical performance?
- Particle color uniformity
- In vitro release profile predictive of in vivo kinetics
- Residual PVA level below 5%
- Vial stopper hardness
Correct Answer: In vitro release profile predictive of in vivo kinetics
Q20. Which byproducts form during PLGA degradation and can lead to local microclimate acidification affecting antigen stability?
- Lactic acid and glycolic acid
- Hydrochloric acid and nitric acid
- Ammonia and carbon dioxide
- Boric acid and citric acid
Correct Answer: Lactic acid and glycolic acid

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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