Vaccine efficacy:
Hib conjugate vaccines are very immunogenic. Studies have shown excellent seroprotection and high antibody titres following vaccination with PRDT & HbOC vaccines. As discussed before PRP OMP is a good vaccine for first dose protection but not as immunogenic at the end of the schedule. PRP-O is the least immunogenic & hence not approved for use for primary dose but only as booster dose.

98-100% of vaccines develop titres >0.15 mcg/ml at the end of 3 doses and GMT achieved is also high in the range of 4-6 mcg/ml. The antibody titres fall over next 1 year. 90% still have titres >0.15 by 18-24 months. A booster given at 15-18 months leads to 100% of vaccinees reaches >0.15mcg/ml level and GMT gets boosted by 60-70 times to a level of 60-90 mcg/ml. (12)

One of the study on PRPT shown the kinetic of antibody development as seen in table IV. One can see that 50% are protected by first dose, 95% by second dose and 99% by 3^rd dose of vaccines & 100% by the booster dose. The GMT at the end of 3 doses is 5.4mcg/ml which falls to 1.22 mcg/ml by 18 months & reaches a high level of 84.7 mcg/ml after the booster dose. (17)

Table IV : Kinetics of anti PRP antibody following PRPT vaccine PRPT +DPT / IPV at 3, 4, 5 months

Anti PRP	Pre	>1 dose	> 2 dose	>3 dose	18 mths	> booster
>0.15 mcg/ml(%)	18.6	89.1	95.9	99.3	89	100
>1.0 mcg/ml (%)	1.8	7.6	78.1	89.8	53.9	100
GMT	0.05	0.17	2.96	5.43	1.22	66.8

PRP OMP and HbOC vaccine with adjuvant lead to 80% of vaccinees achieving a titre of >0.15 mcg by first dose itself. After this the titres for PRP OMP are not boosted with subsequent doses whereas HbOC with adjuvant vaccine shown similar titres & % seroprotection as PRPT or HbOC without adjuvant.

Similar results have been obtained in studies done on infants from developing countries like Gambia, Alaska, Chile, Philippines, India etc 18).

Comparison :
One study compared 4 vaccines viz. PRP D,PRP OMP, PRPT & HbOC vaccine for their immunogenicity as shown in table V. HbOC vaccine with adjuvant is recently available & data on this vaccine is shown in table VI.

Table V : Comparison of immunogenecity of various Hib vaccines (16)

Anti PRP mcg/ml	PRP OMP	HbOC	PRPT	PRPD
Pre GMT	0.11	0.07	0.10	0.07
>1st GMT	0.8	0.1	0.1	-
>2nd GMT	0.8	0.3	0.3	0.08
>3rd GMT	1.14	3.08	3.64	0.28
% > 0.15	92.0	93.0	99.0	58.0
% > 1.0	55.0	75.0	83.0	28.0

Table VI : Kinetics of antibody after HbOC with adjuvant

Anti PRP mcg / ml	> 1st dose	> 2nd dose	> 3rd dose
% > 0.15	80	100	100
% > 1.0	45	91	100
GMT	0.75	5.4	22.4

It shows that PRPT & HbOC vaccines are excellent vaccines with protection in 50% with first dose and 95% of vaccinees with 2^nd dose onwards. The % seroprotection & GMT are comparable though the titres are marginally better with PRPT than with HbOC in this study. PRP OMP was good as far as first dose protection which was achieved in majority but the titres did not get boosted with subsequent doses. PRP D was the least immunogenic with <60% seroprotected after 3 doses.

HbOC with adjuvant vaccine shows protection in 80% with first dose, 100% with second dose & the 3^rd dose acts as a booster. The titres at the end of 3^rd dose were 22.4 mcg/ml with this vaccine. There is one study comparing HbOC without adjuvant with HbOC with adjuvant. It showed that 93% of infants achieved titres of >0.15 mcg/ml with both the vaccines & 7-8% & 6% of infants achieved titres of >1.0 mg/ml at the end of 3 doses with adjuvant vaccines & non adjuvant vaccines respectively. This shows that both these vaccines are similar and excellent in efficacy.