Papers

Immunological response to conjugate vaccines in infants: follow up study

D Goldblatt, senior lecturer, ^a E Miller, head, ^b N McCloskey, research fellow, ^a K Cartwright, group director. ^c

^a Immunobiology Unit, Institute of Child Health, London WC1N 1EH, ^b Immunisation Division, Public Health Laboratory Service, Communicable Disease Surveillance Centre, London NW9 5EQ, ^c Public Health Laboratory, Gloucester Royal Hospital, Gloucester GL1 3NN

Correspondence to: Dr Goldblatt d.goldblatt{at}ich.ucl.ac.uk

Immunising infants against Haemophilus influenzae type b with conjugate vaccines has reduced rates of invasive disease in the developed world. Reports from the Gambia suggest that this vaccine has a similar potential for the developing world.¹ The World Health Organisation is considering whether to provide these new vaccines as part of its expanded programme of immunisation.²

A booster dose of the conjugate vaccine administered in the second year of life is generally considered necessary to induce long term immunity against H influenzae type b. This may limit the use of these conjugate vaccines in the developing world where vaccines are administered at 6, 10, and 14 weeks of age under the WHO's immunisation programme; delivery of further vaccinations are associated with logistical problems. In the United Kingdom, infant immunisation takes place in an accelerated fashion at 8, 12, and 16 weeks of age and no booster dose of the conjugate vaccine is administered. Evidence of the effectiveness of this schedule has been published,³ but its success in the United Kingdom may be related to the immunisation of all children younger than 5 years of age; this mass immunisation may have abruptly reduced nasopharyngeal carriage and modes of transmission.

To evaluate the effectiveness of the accelerated immunisation schedule in the United Kingdom we investigated whether it primed infants' immune systems for memory responses at the age of 1 year.

	Subjects, methods, and results

Top Subjects and methods Comment References

This study is a follow up of a previously reported study of the interchangeability of two conjugate vaccines against H influenzae type b.⁴ Infants whose immune systems had been primed with a conjugate vaccine administered with diphtheria, tetanus, and pertussis vaccines at 2, 3, and 4 months of age received one of two conjugates, either ActHIB (Pasteur-Mérieux-MSD, Lyon) or HibTITER (Cyanamid-Lederle-Praxis Biologicals, Pearl River, USA) at the age of 1 year. H influenzae type b polysaccharide (polyribosylribitolphosphate) IgG titres were estimated by enzyme linked immunosorbent assay after primary immunisation, and then immediately before and 1 month after the booster dose was administered.

Altogether 516 infants were recruited. Serum samples were obtained from 401 infants before they received a booster dose and 387 infants after they received a booster dose. H influenzae type b polysaccharide IgG responses are shown in the table. The proportions of children who had antibody titres below the minimum protective level of 0.15µg/ml before receiving their booster dose at 1 year of age was higher than previously reported with the more extended primary immunisation schedule.⁵ The mean increase in antibody titre after administration of the booster dose was 803-fold (95% confidence interval 651 to 955).

	Comment

Top Subjects and methods Comment References

This increase in antibody titres after booster immunisation is consistent with an immunological memory response, and shows that the children's immune systems were successfully primed by the three doses of conjugate vaccine they received during infancy. Immunological memory induced by vaccines administered according to the accelerated primary schedule may provide long term protection even when circulating antibody titres are low. Conjugate vaccines against H influenzae type b could be introduced into the expanded immunisation programme of the WHO using a schedule of three doses in infancy and no booster dose. This should enhance deliverability and reduce costs.

	Acknowledgments

Contributors: DG and EM designed the study. KC and EM coordinated the recruitment of patients and their follow up. DG and NM were responsible for developing the laboratory assay. The paper was written by all the authors. DG is guarantor for the study.

Funding: Medical Research Council. DG is a Wellcome Trust Fellow.

Conflict of interest: None.

	References

Top Subjects and methods Comment References

1. Mulholland K, Hilton S, Adegbola R, Usens S, Oparaugo A, Omosigho C, et al. Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate for prevention of pneumonia and meningitis in Gambian infants. Lancet 1997; 349: 1191-1197[Medline].
2. Steinhoff MC. Haemophilus influenzae type-b infections are preventable everywhere. Lancet 1997; 349: 1186-1187[Medline].
3. Booy R, Heath PT, Slack MPE, Begg N, Moxon ER. Vaccine failures after primary immunisation with Haemophilus influenzae type-b conjugate vaccine without booster. Lancet 1997; 349: 1197-1202[Medline].
4. Goldblatt D, Fairley CK, Cartwright K, Miller E. Interchangeability of conjugated Haemophilus influenzae type b vaccines during primary immunisation of infants. BMJ 1996; 312: 817-818[Free Full Text].
5. Decker MD, Edwards KM, Bradley R, Palmer P. Responses of children to booster immunization with their primary conjugate Haemophilus influenzae type B vaccine or with polyribosylribitol phosphate conjugated with diphtheria toxoid. J Pediatr 1993; 122: 410-413[Medline].

(Accepted 16 December 1997)