Safety and immunogenicity of the DTP/HB /Hib combination vaccine: phase I study

Kusnandi Rusmil; Eddy Fadlyana; Novilia Sjafri Bachtiar; Hadyana Hadyana

doi:10.14238/pi53.6.2013.309-14

Kusnandi Rusmil Department of Child Health, Padjadjaran University Medical School Hasan Sadikin Hospital Bandung
Eddy Fadlyana Department of Child Health, Padjadjaran University Medical School Hasan Sadikin Hospital Bandung
Novilia Sjafri Bachtiar Department of Child Health, Padjadjaran University Medical School Hasan Sadikin Hospital Bandung
Hadyana Hadyana Department of Child Health, Padjadjaran University Medical School Hasan Sadikin Hospital Bandung

DOI: https://doi.org/10.14238/pi53.6.2013.309-14

Keywords: DTP/HB/Hib vaccine, safety, immunogenicity, phase I

Abstract

Background The World Health Organization (WHO) has
recommended the introduction ofhepatitis B (HB) and Haemophilus
influenza type b (Hib) vaccines into routine childhood vaccination
programs. A new diptheria/tetanus/pertussis (DTP) /hepatitis B/Hib
pentavalent combination vaccine has been developed.
Objective To evaluate the safety and immunogenicity of a new
combination DTP/HB/Hib liquid vaccin e in infants.
Met hods An open-label, uncontrolled, prospective intervention
phase I study was con ducted on 30 healthy infants aged 6- 11
weeks. Each subject received 3 doses of DTP/HB/Hib vaccine,
formulated by Bio Fanna, 0.5 mL intramuscularly at the left
anterolateral thigh region using a 25-gauge n eedle of 25 mm
length . Subjects were followed for 1 month after administration of
each vaccine dose to evaluate its safety, while serum anti-diphteria,
tetanus, HB, Hib, and per tussis antibodies were measured prior
to the l '' dose and 1 month after the Jtd dose.
Results Among 30 vaccinated subjects, 18 infants had fever within
24 hours after the first vaccination. Most cases of fever were mild
in intensity and resolved within 24 hours. No other systemic or
local reactions, or serious adverse events were observed in our
subjects during the study. The immunogenicity results after Jtd
vaccine dose showed that the geometric mean titer of the antipolyribosylribitol
phosphate (PRP) antibody levels increased
significantly from 0.0041Î¼,g/mL to 4.3 7 Î¼,g/mL after vaccination,
and most infants h ad a fourfo ld or greater rise in antibody levels
over their pre-injection levels . All subjects who received DTP/
HB/Hib liquid vaccine had seropro tective antibodies against
tetanus, diphtheria,a and hepatitis B, while 29/30 infants had
seroprotective antibodies against pertussis.
Conclusion This new diphtheria/tetanus/pertusis/hepatitis B/Hib
combination vaccine has excellent safety profile and antibody
responses in infants. These results encourage further clinical
evaluation in phase II.

References

1. Looker C and Kelly H. No-fault compensation fo llowing
adverse events attributed to vaccination: a review ofintemational
programmes. Bull World Health Organ 20 11;89:371-
378.
2. World Health Organization. Hepatitis B Vaccine. WHO.
Wkly Epidemiol Rec 2009;40:405- 19.
3. Gessner BD, Sutanto A, Lineh an M, Djelantik IG, Fletcher
T, Gerudug IK et al. Incidences of vaccine-preventable
Haemophilus influenza type b pneumonia and meningitis inIndonesian children: hamlet-randomized vaccine-probe trial.
Lancet 2005;365:43-52.
4. Kartasamita CB, Krishna E, Murad C, Sudigdoadi S, Rendieni
Y. Haemophilus influenza serotypes distribution and antimicrobial
resistance in children with non-severe pneumonia.
Proceedings of the 25th International Congress of Pediatrics
2007 August 25-30, Athens-Greece; 2007.
5. Wenger JD, Hightower AW, Facklam RR, Gaventa S, Broome
CV. Bacterial meningitis in the United States, 1986: Report
of multistates surveillance study. The Bacterial meningitis
Study Group. J Infect Dis 1990;162: 1316-23.
6. International Conference on Harmonization ICH Guidance
E 10: Choice of Control Group and Related Issues in Clinical
Trials; [cited 2012 Feb 2). Available from: http://www.ich.
org/fileadmin/ICH/Guidelines/ElO/pdf.
7. International Conference on Harmonization ICH Guideline.
Ethnic factors in the acceptability of foreign clinical data ES;
[cited 2011 Jan 8]. Available from: http://www.ich.org/LOB/
media/MEDIA436.pdf.
8. International Conference on Harmonization ICH Guideline.
Clinical Safety Data Management Definition and Standards
for Expedited Reporting E2A; [cited 2011 Jan 8]. Available
from: http//private ich org/LOB/media /MEDIA436/pdf.
9. BPOM Badan Pengawas Obat clan Makanan (2001) Pedoman
Cara Uji Klinik yang Baik (CUKB) di Indonesia (Guidelines
for Good Clinical Practice in Indonesia), Jakarta, Indonesia;
2001.
314 â€¢ Paediatr Inaones , Vol. 53, No. 6, November 2013
10. Lequin. "Enzyme immunoassay (EIA)/enzyme-linked immunosorbent
assay (ELISA)". Clin. Chem. 2005: 2415-8.
11. Galazka, A. M.: The immunological basis for immunisation
series. Module 2: Diphtheria. WHO/EPI/GEN, Geneva 1993,
p. 5-10.
12. Horne AD, Lachenbruch PA, Gesner PR, Hsu HS. Analysis
of studies to evaluate immune response to combination vaccine.
Clin Infect Dis 2001; 33: S306-ll.
13. Granoff DM. Assesing efficacy of Haemophilus influenzae
type b combination vaccines. Clin Infect Dis 2001; 33: S27 8-
87.
14. Faingeziast I, Avila-Aquorro ML, Cervantes Y, Fourneau
Marc, Costa-Clemens Sue Ann. Primary & booster vaccination
with DTPw-HB/Hib pentavalent vaccine in Costa
Rican children who had received a birth dose of hepatitis B
vaccine. Pan AmJ Public Health 2002; 12: 247-57.
15. Douglas RG, Sadoff J, Samant V. The vaccine industry. In:
Plotkin S, Orenstien W, Offit P, editors. Vaccines. Amsterdam:
Elsevier; 2008. p. 37-44.
16. Tregnaghi M, L6pez P, Rocha C, Rivera L, Pierre David M,
Riittimann R, and Schuerman L. A new DTPw-HB/Hib
combination vaccine for primary and booster vaccination of
infants in Latin America. Rev Panam Salud Publica 2006;
19(3): 179-87 .
17. Andre FE. Development and clinical application of new
polyvalent combined paediatric vaccines. Vaccine 1999; 17:
1620-7.