Inactivated vaccines usually require:
Inactivated vaccines usually require multiple doses and periodic boosters to achieve and sustain protective immunity because non replicating antigen provides transient immune stimulation. Initial dose primes naive B cells in draining lymph nodes producing low affinity IgM and modest IgG, small memory pool, titer often below correlate of protection threshold. Second dose administered 4-8 weeks later triggers anamnestic response with larger germinal center reaction, extensive somatic hypermutation in dark zone mediated by activation induced cytidine deaminase, affinity maturation, isotype class switching to IgG1 and IgG3 high neutralizing activity, expansion of long lived plasma cells homing bone marrow. Third dose further raises affinity. However antibody wanes over months to years because antigen depot cleared quickly unlike replicating live vaccine persisting weeks. Therefore boosters at 12-18 months and school entry maintain immunity. Examples hepatitis B series three doses at 0,1,6 months achieving seroprotection 95 percent, IPV three doses plus booster, DTP five doses. Reliance on multiple doses impacts compliance, coverage, programmatic cost, requiring tracking immunization records, reminder systems. Adjuvants reduce number but still need repeat exposures; oral live vaccines require single dose.
Ref: Plotkin Why inactivated needs multiple doses; WHO Immunization schedule; Amanna Duration.