Economisation of vaccination against Haemophilus influenzae type b: a randomised trial of immunogenicity of fractional-dose and two-dose regimens.
BACKGROUND
The cost of Haemophilus influenzae type b (Hib) conjugate vaccines has limited their use in non-industrialised countries. To identify more economical vaccination schedules, we carried out a randomised trial of the immunogenicity of alternative regimens to the standard three-dose series.


METHODS
627 Chilean infants were randomly allocated to one of four regimens with either Hib polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) or Hib oligosaccharide-diphtheria mutant toxoid conjugate vaccine (PRP-CRM197), for a total of eight groups. All infants receive diphtheria-tetanus-pertussis (DTP) vaccine at ages 2, 4, and 6 months. The regimens included three full doses, three fractional doses consisting of one half or one third of the full dose, and a regimen of two full doses (at age 4 and 6 months). The primary outcome was the proportion of infants with serum anti-polyribosylribitol phosphate (PRP, the type b capsular polysaccharide) concentrations of 0.15 microg/mL or more at age 8 months.


RESULTS
93% (95% CI 85-98) of infants vaccinated with three full doses of PRP-T or PRP-CRM197 (95% CI 84-98) achieved anti-PRP concentrations of 0.15 microg/mL or more at age 8 months, compared with 91% (83-96) to 100% (95-100) of infants immunised with any fractional-dose regimen. Of the infants vaccinated with two doses of PRP-T or PRP-CRM197, 99% (93-100) and 87% (77-93) developed anti-PRP concentrations of 0.15 microg/mL or more, respectively.


CONCLUSIONS
91% (83-96) to 100% (95-100) of infants immunised with one-half or one-third of a full dose of Hib conjugate developed protective antibody concentrations. Carrier priming with DTP may make two-dose schedules an option in some places. These alternative regimens could bring the cost of Hib vaccines within reach of countries that currently cannot afford them.
Lagos
R
R
Servicio de Salud Metropolitano Norte, CVD, Chile Hospital Roberto Del Rio, Independencia Santiago.
Valenzuela
M T
MT
Levine
O S
OS
Losonsky
G A
GA
Erazo
A
A
Wasserman
S S
SS
Levine
M M
MM
D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000191:economics; D002677:Chile / Q000453:epidemiology; D003365:Costs and Cost Analysis; D003906:Developing Countries; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage; D004306:Dose-Response Relationship, Immunologic; D006192:Haemophilus Infections / Q000453:epidemiology / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000191:economics; D019741:Haemophilus influenzae type b; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000191:economics; D014611:Vaccination / Q000191:economics*; D017778:Vaccines, Combined / Q000008:administration & dosage; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000191:economics
D001426:Bacterial Proteins; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate; D014614:Vaccines, Synthetic; C061963:HibTITER protein, Haemophilus influenzae