Q. Immunity against H. influenzae is predominantly of IgG class and virtually every one above 5 years of age is immune. Then why this immunity in mother doesn't protect infants like that of measles where transplacental transfer of IgG antibodies protect infants against measles upto 6-9 months of age?

Due to transfer of maternal IgG anti-bodies, measles vaccination is advised at 9 months of age or later but Hib vaccination is recommended from 2 months of age onwards. Does it mean that IgG antibodies against H. influenzae serotype b doesn't cross placenta or it is short lived unlike measles? What accounts for such difference seen in transplacental transfer of IgG anti-bodies against measles and Hib?
 

Ravi Goyal,
581-A, Talwandi,
Kota 324 005,
Rajasthan,
India.
 

Dr. Goyal has raised a very interesting and important question regarding immunity to Haemophilus influenzae in general and to H. influenzae type b (Hib) in particular.

Protection against several virus diseases such as measles and poliomyelitis correlates very well with the presence of virus neutralising antibody which can be detected and measured relatively easily. The neutralising antibody is usually targeted at a limited number (sometimes just one) of surface protein epitopes of the virus. The Ig G class antibody transferred transplacentally from the mother is highly protective against measles as long as it remains in the infant's body fluids even in trace amounts. Therefore, such protection may last for a few months in most infants, for 6 months in some and upto 9-11 months in a few, depending upon how much antibody was obtained.

The antigenic epitopes on bacteria are more numerous and more complex. Protection against bacterial diseases do not correlate well with antibodies specific to individual epitopes, except in a few cases such as the capsular polysaccharides of H. influenzae b, the pneumococcus, the meningococcus and Salmonella typhi. Often, protection due to immunity is less robust than in the case of virus diseases, as illustrated by typhoid fever and pertussis that may occur in spite of immune response to their vaccines or even to infection itself. Laboratory methods for the detection and quantitation of antibodies to such specified antigens are difficult and only specialized centers usually perform these tests.

There are capsulated and non-capsulated H. influenzae; the capsulated ones are typed (types a to f) and the others are non-typable. Most non invasive disease such as otitis media, sinusitis, bronchitis and conjunctivitis are caused by the non-typable ones. Invasive diseases such as meningitis, bacteremic disease leading to arthritis, empyema, etc. are caused by type b H. influenzae in the majority of instances. Pneumonia may be caused by type b, other types or untypable organisms.

It is the invasive disease that is predominantly in infancy and early childhood; meningitis, cellulitis, arthritis, etc. due to Hib is very rare beyond 3 to 5 years. On the other hand, otitis media, sinusitis, bronchitis or pneumonia either due to non-typable organisms, or even capsulated organisms in the case of pneumonia, may occur even later, right upto adult age and old age.

The best available correlate to protection against invasive Hib disease is the presence of antibody to the poly ribitol phosphate (PRP) which constitutes the capsular polysaccharide. Serum levels of PRP antibody sufficient for protection are usually found in the sera of infants upto 2 months of age. Obviously it is derived transplacentally from the mother, hence it would be IgG class. Since protection (and protective levels of antibody) last only 2-3 months after birth, obviously very low levels are passively transferred, indicating very low IgG anti PRP antibodies in adults.

Polysaccharide antigens such as PRP are "T cell independent"; the infant's ability to respond to such antigens mature gradually, and is reasonably good by 18 months to 2 years of age. Even in infants colonized by Hib, PRP antibody is not detected, or is lower than the protective level. Only after 2-3 years do they produce PRP antibody, which explains the susceptibility of infants to invasive Hib disease. The anti- body produced is predominantly of the IgM class.

In summary, the answer to Dr. Goyal's question is that the naturally acquired anti- body against the capsular antigen of Hib is usually of low levels and predominently of IgM class, and the IgG-specific antibody levels are quite low. Therefore, only very low levels are transferred transplacentally; hence passive protection is short lived for one to three months only. The protein-conjugated Hib vaccines are better immunogens than PRP itself and they can be started from 6 weeks or 2 months of age. Being a non-replicating antigen, it is not so readily inhibited as the live mealses virus in the vaccine is inhibited by even traces of maternal antibody. Moreover, Hib vaccines are given as 3 doses during the first 6 months of infancy and any minor inhibitory effect to the first dose will be compensated by the subsequent doses.