Can Hib Vaccine Cause Asthma?
by Heidi White

Can the Haemophilus influenzae type b (Hib) vaccine cause asthma or allergy? I am not aware of any human studies that have specifically looked at the effect of Hib vaccine on asthma. However, a Swiss study1 found that invasive Hib infection (epiglottitis) could possibly be linked to an increase in the rate of asthma and allergies (OR 4.8). There may be a few explanations for this. Firstly, the treatment of a Hib infection with antibiotics, such as cephalosporins (eg cefotaxime or ceftriaxone), may by itself increase the risk of asthma.2 And secondly, cell wall components from the Hib bacteria may also be a cause of asthma.

If invasive Hib infection is able to cause asthma then it may also be possible that the Hib vaccine could also have a similar effect. Animal studies have provided various mechanisms for why this could occur:

a) A nasal Hib vaccine has been shown to stimulate Th1 and Th2 cells in mice.3 If the Th2 side of the immune system is over stimulated, then this can increase the risk of asthma and allergy.

b) Hib vaccination in rats has been shown to enhance histamine levels with a corresponding increase in the number of eosinophils.4-7 Eosinophils (white blood cells, used to fight infection) will proliferate and accumulate in the airways under stimulation by interleukin-5 (IL-5), a cytokine produced by Th2 cells. Eosinophil accumulation is also evident in the dermis of the skin seen in people with atopic dermatitis (eczema).

c) Hib vaccination in rats has been shown to cause increased bronchoconstriction in response to histamine, possibly due to an increased reactivity of the para-sympathetic/cholinergic pathways.7,8

d) Studies in guinea-pigs have shown that Hib vaccination may impair the beta (b ) 2-adrenergic system by causing a blocking or desensitization of b 2 receptors, or by reducing the number of b 2 receptors in the lung.9-13 Inhibition of b receptors can lead to increased bronchoconstriction. It is thought that the polysaccharide component of the bacterial cell wall may be responsible for this effect.14 HibTitre vaccine contains purified polysaccharide (PRP), from the capsule of the Hib bacteria, which is linked to a diphtheria carrier protein. PedvaxHIB vaccine contains PRP linked to a meningococcal protein.

It would be interesting to see the results of a human study that specifically examines the effects of Hib vaccine on the incidence of asthma and allergy.

Heidi White

Hospital Pharmacist

September, 1999.



  1. Muhlemann K et al. Risk factors for invasive Haemophilus influenzae disease among children 2-16 years of age in the vaccine era, Switzerland 1991-1993. The Swiss H. Influenzae Study Group. Int J Epidemiol 1996 Dec;25(6):1280-5
  2. Farooqi IS, Hopkin MH. Early childhood infection and atopic disorder. Thorax 1998 November; 53: 927-932
  3. Kurono Y et al. Nasal immunization induces Haemophilus influenzae-specific Th1 and Th2 responses with mucosal IgA and systemic IgG antibodies for protective immunity. J Infect Dis 1999 Jul;180(1):122-32
  4. Nijkamp FP et al. Facilitation of histamine release in the Haemophilus influenzae vaccinated experimental animal. Br J Pharmacol. 1980 Jan; 68(1):147P
  5. Raaijmakers JA, Terpstra GK, Kreukniet J. Mast cells as a possible source of Haemophilus influenzae-induced changes in plasma and lung histamine levels. Int Arch Allergy Appl Immunol 1980;61(3):352-7
  6. Terpstra GK, Raaijmakers JA; Kreukniet J. Comparison of vaccination of mice and rats with Haemophilus influenzae and Bordetella pertussis as models of atopy. Clin Exp Pharmacol Physiol 1979 Mar-Apr;6(2):139-49
  7. Terpstra GK et al. Effects of Haemophilus influenzae vaccination on the (para-)sympathic- cyclic nucleotide-histamine axis in rats. Ann Allergy 1979 Jan; 42(1):36-40
  8. Schreurs AJ, Nijkamp FP. Bronchial hyper-reactivity to histamine induced by Haemophilus influenzae vaccination. Agents Actions 1984 Oct; 15(3-4): 211-5
  9. Terpstra GK, Kreukniet J, Raaijmakers JA. Changes in beta-adrenergic responses as a consequence of infection with micro-organisms. Eur J Respir Dis Suppl 1984;135:34-46
  10. Schreurs AJ, Terpstra GK et al. The effects of Haemophilus influenzae vaccination on anaphylactic mediator release and isoprenaline-induced inhibition of mediator release. Eur J Pharmacol 1980 Apr 4;62(4):261-8
  11. Schreurs AJ, Versteeg DH, Nijkamp FP. Involvement of catecholamines in Haemophilus influenzae induced decrease of beta-adrenoceptor function. Naunyn Schmiedebergs Arch Pharmacol 1982 Sep; 320(3):235-9
  12. Schreurs AJ, Terpstra GK, Raaijmakers JA, Nijkamp FP. Effects of vaccination with Haemophilus influenzae on adrenoceptor function of tracheal and parenchymal strips. J Pharmacol Exp Ther 1980 Dec;215(3):691-6
  13. Nijkamp FP et al. Inhibition of effects of isoprenaline and adrenaline by Haemophilus influenzae vaccination. Br J Pharmacol. 1980 Jan; 68(1):146P.
  14. Schreurs AJ, Verhoef J, Nijkamp FP. Bacterial cell wall components decrease the number of guinea-pig lung beta-adrenoceptors. Eur J Pharmacol 1983 Jan 28; 87(1):127-32

Journal articles--Hib vaccine & asthma