Hib vaccine

Prior to introduction of the conjugate vaccine, Hib was a leading cause of childhood meningitis, pneumonia, and epiglottitis in the United States, causing an estimated 20,000 cases a year in the early 1980s, mostly in children under five years old. Since routine vaccination began, the incidence of Hib disease has declined by greater than 99%, effectively eliminating Hib as a public health problem. Similar reductions in disease occurred after introduction of the vaccine in Western Europe and developing countries.

After routine use of the vaccine in the United States from 1980 to 1990, the rate of invasive Hib disease decreased from 40–100 per 100,000 children down to fewer than 1 per 100,000.[6]

The CDC and the WHO recommend that all infants be vaccinated using a polysaccharide-protein conjugate Hib vaccine, starting after the age of six weeks. The vaccination is also indicated in people without a spleen.[7]

Haemophilus influenzae type b is a bacterium with a polysaccharide capsule; the main component of this capsule is polyribosyl ribitol phosphate (PRP). Anti-PRP antibodies have a protective effect against Hib infections. Thus, purified PRP was considered a good candidate for a vaccine. However, the antibody response to PRP diminished rapidly after administration. This problem was due to recognition of the PRP antigen by B cells, but not T cells. In other words, even though B cell recognition was taking place, T cell recruitment (via MHC class II) was not, which compromised the immune response. This interaction with only B cells is termed T-independent (TI). This process also inhibits the formation of memory B cells, thus compromising long term immune system memory.[8][9]

PRP covalently linked to a protein carrier was found to elicit a greater immune response than the polysaccharide form of the vaccine. This is due to the protein carrier being highly immunogenic in nature. The conjugate formulations show responses which are consistent with T-cell recruitment (namely a much stronger immune response). A memory effect (priming of the immune system against future attack by Hib) is also observed after administration; indicative that memory B cell formation is also improved over that of the polysaccharide form. Since optimal contact between B cells and T cells is required (via MHC II) to maximize antibody production, it is reasoned that the conjugate vaccine allows B cells to properly recruit T cells, this is in contrast to the polysaccharide form in which it is speculated that B cells do not interact optimally with T cells leading to the TI interaction.[8][9]

In order to remedy these issues, the GAVI Alliance took active interest in the vaccine. GAVI offers substantial subsidization of Hib vaccine for countries interested in using the vaccine, as well as financial support for vaccine systems and safe injections. In addition, GAVI created the Hib Initiative to catalyze uptake of the vaccine. The Hib Initiative uses a combination of collecting and disseminating existing data, research, and advocacy to assist countries in the making a decision about using the Hib vaccine. Currently, 61 out of 72 low-income countries are planning on introducing the vaccine by the end of 2009.[10]

The first Hib vaccine licensed was a pure polysaccharide vaccine, first marketed in the United States in 1985.[11] Similar to other polysaccharide vaccines, immune response to the vaccine was highly age-dependent. Children under 18 months of age did not produce a positive response for this vaccine. As a result, the age group with the highest incidence of Hib disease was unprotected, limiting the usefulness of the vaccine. The vaccine was withdrawn from the market in 1988.[12]

The shortcomings of the polysaccharide vaccine led to the production of the Hib polysaccharide-protein conjugate vaccine.[11] The first such vaccine available in the United States was based on work done by American scientists John Robbins and Rachel Schneerson[13] and was available in 1987. Attaching Hib polysaccharide to a protein carrier greatly increased the ability of the immune system of young children to recognize the polysaccharide and develop immunity. There are currently three types of conjugate vaccine, utilizing different carrier proteins for the conjugation process: inactivated tetanospasmin (also called tetanus toxoid); mutant diphtheria protein; and meningococcal group B outer membrane protein.[14]

Multiple combinations of Hib and other vaccines have been licensed in the United States, reducing the number of injections necessary to vaccinate a child. Hib vaccine combined with diphtheria-tetanus-pertussis–polio vaccines and hepatitis B vaccines are available in the United States. The World Health Organization (WHO) has certified several Hib vaccine combinations, including a pentavalent diphtheria-pertussis-tetanus-hepatitis B-Hib, for use in developing countries. There is not yet sufficient evidence on how effective this combined pentavalent vaccine is in relation to the individual vaccines.[15]