| Vaccine description | |
|---|---|
| Target disease | Haemophilus influenzae type b |
| Type | Conjugate vaccine |
| Clinical data | |
| Trade names | ActHIB, Hiberix, OmniHIB, others |
| AHFS/Drugs.com | Professional Drug Facts |
| MedlinePlus | a607015 |
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| Pregnancy category | |
| Routes of administration | IM |
| ATC code | |
| Legal status | |
| Legal status |
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| Identifiers | |
| DrugBank | |
| ChemSpider |
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| UNII | |
| Identifiers | |
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| DrugBank | |
| UNII | |
The Haemophilus influenzae type B vaccine, often called Hib vaccine, is a vaccine used to prevent Haemophilus influenzae type b (Hib) infection. In countries that include it as a routine vaccine, rates of severe Hib infections have decreased more than 90%. It has therefore resulted in a decrease in the rate of meningitis, pneumonia, and epiglottitis.
It is recommended by both the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC). Two or three doses should be given before six months of age. In the United States a fourth dose is recommended between 12 and 15 months of age. The first dose is recommended around six weeks of age with at least four weeks between doses. If only two doses are used, another dose later in life is recommended. It is given by injection into a muscle.
Severe side effects are uncommon. About 20 to 25% of people develop pain at the site of injection while about 2% develop a fever. There is no clear association with severe allergic reactions. The Hib vaccine is available by itself, in combination with the diphtheria/tetanus/pertussis vaccine, and in combination with the hepatitis B vaccine, among others. All Hib vaccines that are currently used are conjugate vaccine.
An initial Hib vaccine was developed in 1977, which was replaced by a more effective formulation in the 1990s. As of 2013, 184 countries include it in their routine vaccinations. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. The wholesale cost of a pentavalent vaccine which includes Hib in the developing world was US$15.40 per dose as of 2014. In the United States it costs about $25–50 per dose.
Medical uses
Hib conjugate vaccines have been shown to be universally effective against all manifestations of Hib disease, with a clinical efficacy among fully vaccinated children estimated to be between 95–100%. The vaccine has also been shown to be immunogenic in patients at high risk of invasive disease. Hib vaccine is not effective against non-type B Haemophilus influenzae. However, non-type B disease is rare in comparison to pre-vaccine rates of Haemophilus influenzae type B disease.
Impact
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 one per 100,000.
Recommendations
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.
Side effects
Clinical trials
and ongoing surveillance have shown Hib vaccine to be safe. In general,
adverse reactions to the vaccine are mild. The most common reactions
are mild fever, loss of appetite, transient redness, swelling, or pain at the site of injection, occurring in 5–30% of vaccine recipients. More severe reactions are extremely rare.
Mechanisms of action
Polysaccharide vaccine
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.
Conjugate vaccine
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.
Developing world
Introduction of Hib vaccine in developing countries lagged behind
that in developed countries for several reasons. The expense of the
vaccine was large in comparison to the standard EPI
vaccines. Poor disease surveillance systems and inadequate hospital
laboratories failed to detect the disease, leading many experts to
believe that Hib did not exist in their countries. And health systems in many countries were struggling with the current vaccines they were trying to deliver.
GAVI and the Hib Initiative
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.
History
Polysaccharide vaccine
The first Hib vaccine licensed was a pure polysaccharide vaccine, first marketed in the United States in 1985. 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.
Conjugate vaccine
The shortcomings of the polysaccharide vaccine led to the production of the Hib polysaccharide-protein conjugate vaccine.
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.
Combination vaccines
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.
