Prevention ofHaemophilus influenzaeType b Colonization by Vaccination: Correlation with Serum Anti‐Capsular IgG Concentration

Abstract

Concentrations of serum anti-Haemophilus influenzae type b (anti-Hib) capsular polysaccharide (CPS) >/=0.15 and >/=1.0 microgram/mL are widely used as surrogates for protection against invasive Hib disease. However, the relationship between serum anti-Hib CPS following immunization and protection against colonization is not known, making it difficult to evaluate new Hib vaccines or combination vaccines. In the Dominican Republic, nasopharyngeal swabs were collected from 546 9-month-old infants who had received Hib conjugate vaccine at ages 2, 4, and 6 months and from 600 unvaccinated infants of the same age. The prevalence of Hib colonization was lower among vaccinated infants than among unvaccinated infants (0.9% vs. 2.3%). Among vaccinated infants, protection against colonization was significantly correlated with anti-Hib CPS concentrations >/=5 microgram/mL 1 month following the third dose of vaccine. These results suggest that the concentration of serum anti-Hib CPS needed for protection against colonization is greater than that needed for protection for invasive disease.

The continuing role ofHaemophilus influenzaetype b carriage surveillance as a mechanism for early detection of invasive disease activity

“…24 Hib colonizes naso and oro pharyngeal mucosa review review >5.0 μg/ml were significantly less likely to be colonized with Hib at nine months of age. 23,57 The impact of herd immunity is said to reduce invasive disease rates by ten times in unvaccinated children under the age of one year compared with pre-vaccination risk. 56,57 A resurgence of Hib disease among Alaskan children in the 1990s, lead authors to suggest that special attention is required to eliminate Hib disease and carriage in high-risk populations.…”

“…25 However, despite the marked disappearance of invasive Hib disease, some studies encompassing mostly Indigenous populations report persisting Hib carriage, albeit at lower levels than pre-vaccination carriage. 2,11,21,23,50,53 The issue of persistent Hib carriage in vaccinated populations occurs globally, mostly in minority populations, often despite high levels of vaccine uptake. 2,12 A study of Native Alaskans reported Hib oropharyngeal carriage as high as 9.3% in fully vaccinated under five year old children.…”

“…Furthermore, Hib carriage surveillance offers feed-back on vaccination effectiveness to vaccine policy makers and, owing to the findings by Fernandez et al persisting carriage in vaccinated individuals may warrant further immunological studies to determine if serum anti-Hib CPS levels provide adequate protection at the mucosal level in all populations. 23 In the light of recent cases of invasive disease from H. influenzae serotype a or non-type b, 103,104 monitoring the true magnitude of all H. influenzae strains may be required. 105 The current vaccination schedules may still be improved upon; as conjugate vaccines offer early protection, but may lack adequate IgA response to protect against carriage at the mucosal interface; and non-conjugate vaccines do not offer early protection; a combination of these two mechanisms for Hib vaccine may well offer a feasible solution.…”

“…21 However, the corollary of vaccination indicates that while conjugate vaccines best promote T-cell-dependent responses, and in-turn a higher serum anti-PRP level, they do not raise the IgA antibody concentration at the mucosal interface. 22 Findings on Hib carriage dynamics from the Dominican Republic, 23 report on serum anti-Hib capsular polysaccharide (CPS) levels between vaccinated and unvaccinated infants of the same age. The results are suggestive that concentrations of serum anti-Hib CPS need to be greater to protect against colonization than for protection against invasive disease.…”

“…The results are suggestive that concentrations of serum anti-Hib CPS need to be greater to protect against colonization than for protection against invasive disease. 23 This may indicate a further change in Hib vaccine schedule, which maximizes at an early age, and at the mucosal interface, thus offering colonization protection.…”