Being carbohydrate antigen, PRP is a poor immunogen as it can not stimulate T cells. Instead it can only stimulate B cells. This leads to two problems. One, it is not effective in <18-24 months old children as B cell immunity is not well developed at that age and hence it can be given only for >18-24 months old children. Secondly in absence of T cell assistance it can only induce IgM antibodies which are short lasting & in low titres. Hence PRP failed to induce protection in the most vulnerable period i.e. <18 months of age & it induced short lasting immunity. It also failed to reduce carrier state.

Field studies done in Finland showed good efficacy of PRP vaccine given at 24 months, as the peak of disease occurs during that age in Finland. In other countries like UK, USA where peak occurs early, PRP failed to demonstrate good efficacy given at 18-24 months of age (2)

Conjugated Hib vaccines:
2^nd generation Hib vaccines are conjugated Hib vaccines. Here the PRP is conjugated with a carrier protein. The carrier protein sort of "fools" T cell & induces them to respond to attached PRP. This makes PRP now T cell dependent. The advantages of conjugate vaccine are 3 folds. Firstly, it is effective from 6 weeks of age onwards. Secondly, it induces IgG antibodies & leads to boosting on repeated doses leading to better short term & long term immunity. Being T cell dependent it stimulates memory T cells which will lead is anamnestic response even years later. Lastly it also induces IgA antibodies which are secreted in nasal secretions. This will postpone & reduce the chances of carrier rate leading to herd immunity.

Types of conjugated Hib Vaccines:
The conjugate Hib vaccines differs from one another depending on the size of the PRP molecule, the type of carrier protein, the type of linkage between PRP & carrier protein and presence or absence of an adjuvant in the vaccine as shown in table III.

PRP-T:
This vaccine has tetanus toxoid as the carrier protein which is attached to PRP via 6 carbon linkage or carbodimide condensation. It contains 10mcg-15mcg of large PRP per dose & has 30mcg of tetanus toxoid. It is an excellent & potent vaccine with proven field efficacy in many trials. It has no adjuvant. It is effective from 6 weeks of age onwards.

Table III : Types of Hib conjugate vaccine


Anti PRP antibody:
All the vaccines induce anti PRP antibodies which are protective. In past, when PRP was the only vaccine available 2 levels of antibodies were taken as significant. Titres >0.15 mcg/ml were taken as protective for immediate but short term period where as titres>1.0mcg/ml were taken as high titres which will protect for long term up to 5 yrs of life. This is because PRP was effective only>18-24 months leading to poor titres & no boosting effec

Now with availability of conjugate vaccine there is T cell response which leads to very high titres, IgG type of antibodies and boosting effect due to T memory cells. Hence all such vaccines will naturally lead to long term protection. Even if titres fall there will anamnestic response on exposure to Hib. Hence titres of >1.0mcg/ml is probably irrelevant today. Yet more studies talk of cut off levels of >0.15 mcg/r ml & >1.0 mcg/ml while describing immune response to vaccine (2).t.