In total, 47 of the 50 infants enrolled to the study completed the primary series of three vaccine doses. Serum sample was available from 49 infants before and from 47 after the three vaccine doses. The reasons for withdrawal included: parental request (1) and transfer of residence (1). One infant did not continue vaccination series due to a hypotonic hyporesponsive episode following immunization.
There were 28 boys (56%) and 23 girls (44%). The mean ages of infants at each vaccination visit were 7.1 weeks (range: 6–8 weeks) at dose 1; 11.2 weeks (range: 10–13 weeks) at dose 2; 15.6 weeks (range: 14–18 weeks) at dose 3 and 19.5 weeks (range 18–23 weeks) on the fourth visit when the post vaccination serum sample was collected.
The most common local reactions in the order of frequency were induration, pain, swelling and redness (Table ). The rate of local reactions between the two injection sites, those associated with the study vaccine and the DTwP//PRP-T vaccine were almost of equal frequency following each of the three doses, except for induration. The rate of induration was significantly more common after all of the three doses in the DTwP//PRP-T vaccine than the study vaccine: following dose 1 (45.1 % vs. 8.0 %, p < 0.001); dose 2 (30.6 % vs. 10.2 %, p < 0.01) and dose 3 (19.1% vs. 4.2%, p < 0.02).
Local reactions (%) within the first 5 days after vaccination in infants receiving three doses of DTwP//PRP-T, OPV, hepatitis B and the 11PncTD conjugate vaccines
The clinical parameters included in the evaluation of systemic events after each dose included fever, vomiting, diarrhoea, inconsolable crying, unusual drowsiness, irritability, anorexia and insomnia (Table ). The rate of fever (≥ 38°C) after each of the three doses were 39.2%, 22.4% and 21.3%. Fever of 38.7°C or more occurred at 8.0 %, 12.2% and 8.5% of the infants. All local and systemic reactions resolved without medical intervention. There was a trend in the frequency of both local and systemic reactions to decrease with successive doses of vaccine.
Systemic reactions (%) within the first 5 days after vaccination in infants receiving three doses of DTwP//PRP-T, OPV, hepatitis B and the 11PncTD conjugate vaccines
There were nine serious adverse events, which consisted of eight hospitalisations. The reasons included: one case of suspected meningitis, 2 cases of acute gastroenteritis, 3 cases of bronchopneumonia, one case of bronchitis and one urinary tract infection. The patient with suspected meningitis had received immunization 17 days before the onset of fever and convulsions, which led to death very soon after admission to hospital. The aetiology of infection remained unconfirmed. All these adverse events were reported as not related to the study vaccine by the investigators. There was one hypotensive hyporesponsive episode that occurred 20 minutes after administration of 11-PncTD and DTwP//PRP-T vaccines. The episode resolved within 15 minutes and was considered as probably study vaccine related. Another case of cyanosis of the lips and nails, fever and chills was reported the day of the third vaccination and was considered as probably related to the vaccination by investigators. At follow-up, this event was re-evaluated as being non-serious. The investigator decided however to withdraw the subject from the study.
The GMCs of antibodies before and after three vaccine doses of the 11-PncTD vaccine are summarised in Table . The pre-vaccination GMCs at 6 weeks of age varied between 0.27 μg/ml for serotype 4 and 1.61 μg/ml for type 14. After three vaccine doses, all GMCs of antibodies, except for serotype 14 (p = .253) were significantly higher than before the vaccination series. At 18 weeks, all infants had antibody concentration > 1.0 μg/ml against serotypes 1, 3, 4, 5, 7F, 9V, and 19F whereas 49, 83, 91.5 and 87.2 % of infants had concentration > 1.0 μg/ml against serotypes 6B, 14, 18C, and 23F, respectively.
Geometric mean concentration (GMC, μg /ml) and 95 % confidence intervals (CI) of antibodies against pneumococcal serotypes included in the 11-valent pneumococcal vaccine given at 6, 10 and 14 weeks of age in Filipino infants