RTS,S vaccine limitations — DTM&H MCQ

Correct answer: C — Efficacy wanes over time requiring boosters

The correct answer is C, efficacy wanes over time requiring boosters. RTS,S/AS01 (Mosquirix) demonstrated around 40 percent efficacy against clinical malaria and roughly 30 percent against severe disease in the pivotal phase 3 paediatric trial, but this protection is not durable. <cite index="3-1">Efficacy wanes after one year, necessitating a booster dose to provide protection through early childhood.</cite> This waning reflects rapid decline of anti-circumsporozoite antibody titres after the primary three dose series, which is why WHO's implementation programme mandates a fourth (booster) dose around 18 months after the primary course to sustain partial protection. This time dependent decay, rather than cost, adverse effects, or species specificity, is the recognised primary limitation driving the multi-dose schedule. Why the other options are wrong: B. Too expensive for resource-limited settings: cost and supply constraints are real implementation challenges but are not the biological limitation identified by trial data on waning immunity, and the vaccine is specifically funded and rolled out via Gavi for exactly these settings. E. Severe adverse events in 10% of recipients: phase 3 trials showed a favourable safety profile with only a signal for febrile seizures shortly after vaccination, not a 10 percent severe adverse event rate. A. No protection against P. vivax: RTS,S targets the circumsporozoite protein of Plasmodium falciparum specifically; lack of vivax coverage is expected by design and irrelevant in Burkina Faso, where falciparum predominates, so this is not the trial's discriminating limitation. D. Works only in adults: RTS,S was developed and licensed specifically for young children in endemic African settings (age 5 to 17 months at first dose), the opposite of this claim. Key point: RTS,S provides only partial, time-limited protection because antibody titres decay rapidly, which is why a fourth booster dose is required to sustain efficacy in the WHO-recommended schedule.

Reference: PMC (Cambridge/Elsevier hosted review), 'RTS,S today and tomorrow's science', 2023, https://pmc.ncbi.nlm.nih.gov/articles/PMC10317573/