• Vaccine Name: Killed nontypeable H. influenzae whole-cell vaccine
• Target Pathogen: Haemophilus influenzae
• Target Disease: Meningitis
• Vaccine Ontology ID: VO_0000474
• Type: Inactivated or "killed" vaccine
• Antigen: whole cell
• Preparation: The vaccine was enteric-coated tabletcontaining 10th power numbers of killed H influenzae with sodium tauroglycocholate. The organism was a non-serotypable biotype 2 H influertzae, and was formalin killed. The tablets were quality controlled for acid resistance, release in alkali, and sterility of content (Clancy et al., 1985).
• Immunization Route: Oral immunization
• Virulence: no virulence
• Description: Acute exacerbations of bronchitis and chronic obstructive pulmonary disease often occur in people with compromised respiratory function.The bacterial agents responsible for the acute exacerbations are commonly an expansion of the patient's own respiratory tract microbiota often following the arrival of a new strain of normal commensal. Nontypeable Haemophilus influenzae is of particular importance because it is the most commonly isolated bacterium at times of exacerbation (Foxwell et al., 2006). Successful vaccines for infections caused by H. influenzae serotype B (Hib) depend on immunity stimulated against the type-specific polysaccharide capsule of Hib. But this is not effective against infections caused by organisms lacking the polysaccharide, such as nontypeable H. influenzae. The oral whole-cell nontypeable. H. influenzae vaccine is developed to prevent nontypeable H. influenzae infections (Foxwell et al., 2006).

Human Response

• Vaccination Protocol: A prospective, double-blind, placebo-controlled trial was performed during the Australian winter of 1983. 50 patients with established COLD were recruited from the chest clinic of the Royal Newcastle Hospital and randomly allocated to three groups. No patient was taking corticosteroids or mmunosuppressive agents, but many took bronchodilator drugs and antibiotics. Three groups were tested: one took enteric-coated glucose tablets; the second took enteric-coated tablets containing 25 mg sodium tauroglycocholate; while the third took enteric-coated tablets each containing 10th power of killed H influenzae with sodium tauroglycocholate. Three courses of tablets were given at 0, 28, and 56 days. Each course consisted of two tablets taken before breakfast each day for 3 consecutive days. Each patient was assessed at 0, 28, 56 and 84 days (Clancy et al., 1985).
• Persistence: Over a similar 3-month period through the subsequent winter (1984), during which no tablets were given, 11 of 22 patients available from the combined placebo groups had one or more acute episodes of bronchitis, while 4 of 14 available from the group who had previously taken the H influenzae tablets, had acute episodes. This trend towards continued protection was not significant (Clancy et al., 1985).
• Efficacy: The vaccine provided a more than 9007o protection rate against clinical episodes of acute bronchitis, with no noticeable effect on the incidence of upper respiratory tract infection. No significant difference in the incidence of acute upper respiratory tract infection was detected between the three groups. There was significant reduction in both the number of subjects with episode(s) of acute bronchitis (p<0 . 005), and the absolute number of episodes of acute bronchitis (p<0 . 002), in the group taking tablets containing H influenzae. If results were analysed according to the relative incidence of infection, there was a tenfold reduction in incidence in those taking the active tablet (p<0 . 001) (Clancy et al., 1985). No significant difference in antibody level to HI/H2 antigen existed between the three groups at zero time or at any point in the trial.

Human Response

• Vaccination Protocol: Randomised, double-blind, placebo-controlled study of six months duration including winter. 40 patients with chronic bronchitis, 3 withdrawals, 2 from placebo and 1 from active treatment group. 20 given a placebo, 20 vaccinated. Mean age 46.3, sex ratio (m/f) 8/12 for the placebo group and 47.4, sex ratio 11/9 for the vaccine group. Vaccine consisting of 10 to the 11th formalin killed nontypeable Haemophilus infuenzae in 3 courses of enteric coated tablets given at days 0, 28 and 56. Each course consisted of two tablets given over three consecutive days before breakfast. Placebos were enteric coated glucose tablets (Clancy et al., 1990).
• Efficacy: The vaccine resulted in a marked reduction in the total number of episodes of acute bronchitis and acute wheezy bronchitis concomitant with a reduction in antibiotic use. They also warned that the small group number and a possible favouring of the vaccine group might have occurred. They also demonstrated a prevention of increase of H. inuenzae colonization in the vaccinated group (Clancy et al., 1990).

Human Response

• Vaccination Protocol: Randomised, double-blind, prospective placebo-controlled study of 12 months duration starting in October. 62 patients with chronic bronchitis or more than 2 episodes of acute bronchitis in 2 years. 32 given a placebo,30 vaccinated. Mean age 53.7, sex ratio (m/f) 15/17 for the placebo group and 52.6, sex ratio 15/17 for the vaccine group: Drop-outs were 11 from vaccine group and 4 from placebo group. Vaccine consisting of 10 to the 11th formalin killed nontypeable Haemophilus influenzae in 3 courses of enteric coated tablets given at days 0, 28 and 56. Each course consisted of two tablets given over three consecutive days before breakfast. Placebos were enteric coated glucose tablets (Lehmann et al., 1991).
• Efficacy: the vaccine group had significantly lower acute bronchitic episodes post vaccination than the control group in individuals who had less severe but not severe disease. The carriage rate of H. influenzae also declined in the vaccinated group (Lehmann et al., 1991).

Human Response

• Vaccination Protocol: Randomised, double-blind, placebo-controlled study of 12 months duration starting in March. 77 patients with chronic bronchitis. 10 were withdrawn (7 in placebo group and 3 in vaccine group). 3 from the vaccine group died. 33 given a placebo, 31 vaccinated. Mean age 71.1, sex ratio (m/f) 30/3 for the placebo group and 73.1, sex ratio 22/9 for the vaccine group. Vaccine consisting of 10 to the 11th formalin killed nontypeable Haemophilus influenzae in 3 courses of enteric coated tablets given at days 0, 28 and 56. Each course consisted of two tablets given over three consecutive days before breakfast. Placebos were enteric coated glucose tablets (Tandon et al., 1991).
• Efficacy: A reduction in acute bronchitic episodes in patients who received the vaccine was observed. They also needed to prescribe fewer antibiotics despite the number of individual's requiring antibiotics being similar. A reduction in H. influenzae colonization also occurred in vaccinated individuals (Tandon et al., 1991).